Department of Food Science and Nutrition Associate Professor
Last Updated :2023/11/29

Researcher Information

J-Global ID

Research Interests

  • 公衆栄養学   病態生理学   循環器学   応用栄養学   運動習慣   

Research Areas

  • Life sciences / Nutrition and health science
  • Life sciences / Healthcare management, medical sociology
  • Life sciences / Nutrition and health science
  • Life sciences / Clinical pharmacy
  • Life sciences / Physiology

Academic & Professional Experience

  • 2022/04 - Today  Kindai University農学部食品栄養学科准教授
  • 2019/04 - 2021/03  近畿大学農学部食品栄養学科講師
  • 2016/04 - 2019/03  The University of Tokushima糖尿病対策センター特任講師
  • 2017/09 - 2018/12  Drexel University College of MedicineDept. Pharmacology and Physiology客員研究員
  • 2007/04 - 2016/03  Oita UniversityFaculty of Medicine助教
  • 2006/10 - 2007/04  Oita UniversityFaculty of Medicine研究支援者
  • 2006/04 - 2006/09  Oita UniversityFaculty of Medicine技術補佐員


  • 2003/04 - 2006/03  The University of Tokushima  栄養学研究科  博士後期課程
  • 2001/04 - 2003/03  The University of Tokushima  栄養学研究科  博士前期課程

Association Memberships


Published Papers

  • Mengyan Wei; Pu Wang; Xiufang Zhu; Masaki Morishima; Yangong Liu; Mingqi Zheng; Gang Liu; Hiroki Osanai; Kenshi Yoshimura; Shinichiro Kume; Tatsuki Kurokawa; Katsushige Ono
    PloS one 18 (2) e0280656  2023 
    Gemcitabine is an antineoplastic drug commonly used in the treatment of several types of cancers including pancreatic cancer and non-small cell lung cancer. Although gemcitabine-induced cardiotoxicity is widely recognized, the exact mechanism of cardiac dysfunction causing arrhythmias remains unclear. The objective of this study was to electrophysiologically evaluate the proarrhythmic cardiotoxicity of gemcitabine focusing on the human rapid delayed rectifier potassium channel, hERG channel. In heterologous hERG expressing HEK293 cells (hERG-HEK cells), hERG channel current (IhERG) was reduced by gemcitabine when applied for 24 h but not immediately after the application. Gemcitabine modified the activation gating properties of the hERG channel toward the hyperpolarization direction, while inactivation, deactivation or reactivation gating properties were unaffected by gemcitabine. When gemcitabine was applied to hERG-HEK cells in combined with tunicamycin, an inhibitor of N-acetylglucosamine phosphotransferase, gemcitabine was unable to reduce IhERG or shift the activation properties toward the hyperpolarization direction. While a mannosidase I inhibitor kifunensine alone reduced IhERG and the reduction was even larger in combined with gemcitabine, kifunensine was without effect on IhERG when hERG-HEK cells were pretreated with gemcitabine for 24 h. In addition, gemcitabine down-regulated fluorescence intensity for hERG potassium channel protein in rat neonatal cardiomyocyte, although hERG mRNA was unchanged. Our results suggest the possible mechanism of arrhythmias caused by gemcitabine revealing a down-regulation of IhERG through the post-translational glycosylation disruption possibly at the early phase of hERG channel glycosylation in the endoplasmic reticulum that alters the electrical excitability of cells.
  • Yan Wang; Masaki Morishima; Katsushige Ono
    Membranes 12 (7) 2022/07 
    Two distinct isoforms of the T-type Ca2+ channel, Cav3.1 and Cav3.2, play a pivotal role in the generation of pacemaker potentials in nodal cells in the heart, although the isoform switches from Cav3.2 to Cav3.1 during the early neonatal period with an unknown mechanism. The present study was designed to investigate the molecular system of the parts that are responsible for the changes of T-type Ca2+ channel isoforms in neonatal cardiomyocytes using the whole-cell patch-clamp technique and mRNA quantification. The present study demonstrates that PKC activation accelerates the Ni2+-sensitive beating rate and upregulates the Ni2+-sensitive T-type Ca2+ channel current in neonatal cardiomyocytes as a long-term effect, whereas PKC inhibition delays the Ni2+-sensitive beating rate and downregulates the Ni2+-sensitive T-type Ca2+ channel current. Because the Ni2+-sensitive T-type Ca2+ channel current is largely composed of the Cav3.2-T-type Ca2+ channel, it is accordingly assumed that PKC activity plays a crucial role in the maintenance of the Cav3.2 channel. The expression of Cav3.2 mRNA was highly positively correlated with PKC activity. The expression of a transcription factor Nkx2.5 mRNA, possibly corresponding to the Cav3.2 channel gene, was decreased by an inhibition of PKCβII. These results suggest that PKC activation, presumably by PKCβII, is responsible for the upregulation of CaV3.2 T-type Ca2+ channel expression that interacts with a car-diac-specific transcription factor, Nkx2.5, in neonatal cardiomyocytes.
  • Masaki Morishima; Katsushige Ono
    Heart and vessels 36 (10) 1597 - 1606 0910-8327 2021/10 [Refereed]
    We tested the hypothesis that angiotensin II (Ang II)-induced cardiovascular complications are distinguished from what catecholamine-induced by their serum circulating biomarkers in rats. Infusion of Ang II (1.68 mg/kg/day) significantly increased systolic and diastolic blood pressure assessed at week one or later, accompanied by an increase of heart/body weight ratio. Noradrenaline infusion (5.40 mg/kg/day) produced a similar degree of hypertension, but did not increase heart weight. Ang II-, but not noradrenaline-induced hypertension was associated with a drastic upregulation of serum microRNA-30d (miR-30d) by hundreds of times, accompanied by an increase of miR-30d levels in the atrium but not in the ventricle. Ang II, but not noradrenaline, significantly increased mRNA of brain natriuretic peptide (BNP) in the atrium. Studies using rat neonatal cardiomyocytes in vitro demonstrated that BNP caused an increase of miR-30d when applied for 6 h or longer in the culture medium. In vitro application of Ang II increased the cell size, although BNP and miR-30d were unable to mimic the effect of Ang II. We conclude that serum circulating microRNA-30d is a sensitive biomarker for Ang II-induced cardiovascular complications. It is also postulated that Ang II-induced cardiomyocyte hypertrophy could be independent of miR-30d/BNP signaling pathways.
  • Masaki Morishima; Takafumi Fujita; Satoshi Osagawa; Hiroshi Kubota; Katsushige Ono
    Membranes MDPI AG 11 (7) 470 - 470 2021/06 [Refereed]
    Brain-derived neurotrophic factor (BDNF) has recently been recognized as a cardiovascular regulator particularly in the diseased condition, including coronary artery disease, heart failure, cardiomyopathy, and hypertension. Here, we investigate the role of BDNF on the T-type Ca2+ channel, Cav3.1 and Cav3.2, in rat neonatal cardiomyocytes exposed to normoxia (21% O2) and acute hypoxia (1% O2) in vitro for up to 3 h. The exposure of cardiomyocytes to hypoxia (1 h, 3 h) caused a significant upregulation of the mRNAs for hypoxia-inducible factor 1α (Hif1α), Cav3.1, Cav3.2 and Bdnf, but not tropomyosin-related kinase receptor B (TrkB). The upregulation of Cav3.1 and Cav3.2 caused by hypoxia was completely halted by small interfering RNA (siRNA) targeting Hif1a (Hif1a-siRNA) or Bdnf (Bdnf-siRNA). Immunocytochemical staining data revealed a distinct upregulation of Cav3.1- and Cav3.2-proteins caused by hypoxia in cardiomyocytes, which was markedly suppressed by Bdnf-siRNA. These results unveiled a novel regulatory action of BDNF on the T-type Ca2+ channels expression through the HIF-1α-dependent pathway in cardiomyocytes.
  • Pu Wang; Mengyan Wei; Xiufang Zhu; Yangong Liu; Kenshi Yoshimura; Mingqi Zheng; Gang Liu; Shinichiro Kume; Masaki Morishima; Tatsuki Kurokawa; Katsushige Ono
    Scientific reports 11 (1) 11273 - 11273 2021/05 [Refereed]
    Nitric oxide (NO) is produced from endothelial cells and cardiomyocytes composing the myocardium and benefits cardiac function through both vascular-dependent and-independent effects. This study was purposed to investigate the possible adverse effect of NO focusing on the voltage-gated Na+ channel in cardiomyocytes. We carried out patch-clamp experiments on rat neonatal cardiomyocytes demonstrating that NOC-18, an NO donor, significantly reduced Na+ channel current in a dose-dependent manner by a long-term application for 24 h, accompanied by a reduction of Nav1.5-mRNA and the protein, and an increase of a transcription factor forkhead box protein O1 (FOXO1) in the nucleus. The effect of NOC-18 on the Na+ channel was blocked by an inhibitor of thiol oxidation N-ethylmaleimide, a disulfide reducing agent disulfide 1,4-Dithioerythritol, or a FOXO1 activator paclitaxel, suggesting that NO is a negative regulator of the voltage-gated Na+ channel through thiols in regulatory protein(s) for the channel transcription.
  • Ryusuke Suzuki; Masaki Morishima; Chisato Nakada; Shinji Miyamoto; Katsushige Ono
    Heart and vessels 36 (4) 577 - 588 0910-8327 2021/04 [Refereed]
    This investigation was aimed to identify gene profiles in human atrial myocardium in response to chronic mechanical stretch. Right atrial appendages from 21 patients were divided into 2 groups based on the size of right atrial volume. The microarray DATA analyses differentially identified 335 genes (> 2.0-fold, corrected P < 0.05) including "functionally unknown genes". This study identified 26 up-regulated genes (natriuretic peptide B, G protein subunit gamma 13, thyroid stimulating hormone beta, etc.) and 23 down-regulated genes (oligodendrocyte transcription factor 1, carbonic anhydrase 12, etc.), which could be responsible for chronic stretch-mediated structural remodeling in the atrium.
  • Masaki Morishima; Shintaro Tahara; Yan Wang; Katsushige Ono
    Membranes 11 (4) 234  2021/03 [Refereed]
    Oxytocin (OT) and its receptor (OTR) are expressed in the heart and are involved in the physiological cardiovascular functional system. Although it is known that OT/OTR signaling is cardioprotective by reducing the inflammatory response and improving cardiovascular function, the role of OT in the cardiac electrical excitation modulation has not been clarified. This study investigates the molecular mechanism of the action of OT on cardiomyocyte membrane excitation focusing on the L-type Ca2+ channel. Our methodology uses molecular biological methods and a patch-clamp technique on rat cardiomyocytes with OT, combined with several signal inhibitors and/or activators. Our results show that long-term treatment of OT significantly decreases the expression of Cav1.2 mRNA, and reduces the L-type Ca2+ channel current (ICa.L) in cardiomyocytes. OT downregulates the phosphorylated component of a transcription factor adenosine-3',5'-cyclic monophosphate (cAMP) response element binding protein (CREB), whose action is blocked by OTR antagonist and pertussis toxin, a specific inhibitor of the inhibitory GTP-binding regulators of adenylate cyclase, Gi. On the other hand, the upregulation of Cav1.2 mRNA expression by isoproterenol is halted by OT. Furthermore, inhibition of phospholipase C (PLC) was without effect on the OT action to downregulate Cav1.2 mRNA-which suggests a signal pathway of Gi/protein kinase A (PKA)/CREB mediated by OT/OTR. These findings indicate novel signaling pathways of OT contributing to a downregulation of the Cav1.2-L-type Ca2+ channel in cardiomyocytes.
  • Yan Wang; Masaki Morishima; Dan Li; Naohiko Takahashi; Tetsunori Saikawa; Stanley Nattel; Katsushige Ono
    Circulation journal : official journal of the Japanese Circulation Society Japanese Circulation Society 84 (11) 1931 - 1940 1346-9843 2020/10 [Refereed]
    BACKGROUND: The association between binge alcohol ingestion and atrial fibrillation (AF), often termed "holiday heart syndrome", has long been recognized. However, the underlying cellular and molecular mechanisms are unknown.Methods and Results:An experimental model of binge alcohol-induced AF was developed to elucidate the mechanisms linking acute ethanol exposure to changes in ion channel transcription and AF susceptibility. AF-susceptibility during transesophageal electrical stimulation was enhanced 8 h after, but not immediately or 24 h after, acute alcohol intake. T-type calcium channel (TCC) blockade and calcineurin inhibition diminished the AF-promoting effect of ethanol. Long-term (8-24 h) exposure to ethanol augmented TCC isoform-expression (Cav3.1 and Cav3.2) and currents in cardiomyocytes, accompanied by upregulation of the transcription factors, Csx/Nkx2.5 and nuclear factor of activated T-cells (NFAT), in the nucleus, and of phospho-glycogen synthesis kinase 3β (GSK3β) in the cytosol. Inhibition of protein kinase C (PKC) during the 7- to 8-h period following ethanol exposure attenuated susceptibility to AF, whereas acute exposure did not. GSK3β inhibition itself upregulated TCC expression and increased AF susceptibility. CONCLUSIONS: The present study results suggest a crucial role for TCC upregulation in the AF substrate following binge alcohol-drinking, resulting from ethanol-induced PKC-activation that hyperphosphorylates GSK3β to cause enhanced calcineurin-NFAT-Csx/Nkx2.5 signaling. These observations elucidate for the first time the potential mechanisms underlying the clinically well-recognized, but mechanistically enigmatic, "holiday heart syndrome".
  • Toru Shimaoka; Yan Wang; Masaki Morishima; Shinji Miyamoto; Katsushige Ono
    Circulation journal : official journal of the Japanese Circulation Society JAPANESE CIRCULATION SOC 84 (8) 1244 - 1253 1346-9843 2020/07 [Refereed]
    BACKGROUND: Mechanisms for QT interval prolongation and cardiac arrhythmogenesis in hypomagnesemia are poorly understood. This study investigated the potential molecular mechanism for QT prolongation caused by magnesium (Mg) deficiency in rats by using the patch clamp technique and molecular biology.Methods and Results:Male Wistar rats were fed an Mg-free diet or a normal diet for up to 12 weeks. There was QT prolongation in the ECG of Mg-deficient rats, and cardiomyocytes from these rats showed prolongation of action potential duration. Electrophysiological studies showed that inward-rectifying K+current (IK1) and transient outward K+current (Ito) were decreased in Mg-deficient cardiomyocytes, and these findings were consistent with the downregulation of mRNA, as well as protein levels of Kir2.1 and Kv4.2. In Mg-deficient cardiomyocytes, transcription factors, GATA4 and NFAT, were upregulated, whereas CREB was downregulated. In contrast to Mg deficiency, cellular Mg2+overload in cultured cardiomyocytes resulted in the upregulation of Kir2.1 and Kv4.2, which was accompanied by the downregulation of GATA4 and NFATc4, and the upregulation of CREB. Activation of NFAT and inhibition of CREB reduced Kv4.2-Ito, whereas Kir2.1-IK1was reduced by CREB inhibition but not by NFTA activation. CONCLUSIONS: Intracellular Mg deficiency downregulates IK1and Itoin cardiomyocytes, and this is mediated by the transcription factors, NFAT and CREB. These results provide a novel mechanism for the long-term QT interval prolongation in hypomagnesemia.
  • Kimiko Masuda; Hiroki Takanari; Masaki Morishima; FangFang Ma; Yan Wang; Naohiko Takahashi; Katsushige Ono
    The journal of physiological sciences : JPS SPRINGER JAPAN KK 68 (6) 759 - 767 1880-6546 2018/11 [Refereed]
    Men have shorter rate-corrected QT intervals (QTc) than women, especially at the period of adolescence or later. The aim of this study was to elucidate the long-term effects of testosterone on cardiac excitability parameters including electrocardiogram (ECG) and potassium channel current. Testosterone shortened QT intervals in ECG in castrated male rats, not immediately after, but on day 2 or later. Expression of Kv7.1 (KCNQ1) mRNA was significantly upregulated by testosterone in cardiomyocytes of male and female rats. Short-term application of testosterone was without effect on delayed rectifier potassium channel current (IKs), whereas IKs was significantly increased in cardiomyocytes treated with dihydrotestosterone for 24 h, which was mimicked by isoproterenol (24 h). Gene-selective inhibitors of a transcription factor SP1, mithramycin, abolished the effects of testosterone on Kv7.1. Testosterone increases Kv7.1-IKs possibly through a pathway related to a transcription factor SP1, suggesting a genomic effect of testosterone as an active factor for cardiac excitability.
  • Masaki Morishima; Kazuki Horikawa; Makoto Funaki
    PloS one PUBLIC LIBRARY SCIENCE 13 (8) e0201891  1932-6203 2018 [Refereed]
    RATIONALE: Diabetes causes cardiac dysfunction, and understanding of its mechanism is still incomplete. One reason could be limitations in modeling disease conditions by current in vitro cardiomyocyte culture. Emerging evidence suggests that the mechanical properties of the microenvironment affect cardiomyocyte function. Nevertheless, the impact of high glucose on cardiomyocytes cultured on substrates whose stiffness matches that of the heart (approximately 15 kPa) is untested. OBJECTIVE: To test the hypothesis that cardiomyocytes cultured in microenvironments that mimic the mechanical properties of those for cardiomyocytes in vivo may reproduce the pathophysiology characteristics of diabetic cardiomyocytes ex vivo, such as the morphological appearance, ROS accumulation, mitochondrial dysfunction, apoptosis and insulin-stimulated glucose uptake. METHODS AND RESULTS: Isolated neonatal rat cardiomyocytes were seeded on 15 kPa polyacrylamide (PAA) gels, whose stiffness mimics that of heart tissues, or on glass coverslips, which represent conventional culture devices but are unphysiologically stiff. Cells were then cultured at 5 mM glucose, corresponding to the normal blood glucose level, or at high glucose levels (10 to 25 mM). Cytoskeletal disorganization, ROS accumulation, attenuated mitochondrial membrane potential and attenuated ATP level caused by high glucose and their reversal by a ROS scavenger were prominent in cells on gels, but not in cells on coverslips. The lack of response to ROS scavenging could be attributable to enhanced apoptosis in cells on glass, shown by enhanced DNA fragmentation and higher caspase 3/7 activity in cells on glass coverslips. High-glucose treatment also downregulated GLUT4 expression and attenuated insulin-stimulated glucose uptake only in cells on 15 kPa gels. CONCLUSION: Our data suggest that a mechanically compliant microenvironment increases the susceptibility of primary cardiomyocytes to elevated glucose levels, which enables these cells to serve as an innovative model for diabetic heart research.
  • Fangfang Ma; Hiroki Takanari; Kimiko Masuda; Masaki Morishima; Katsushige Ono
    Heart and vessels SPRINGER 31 (7) 1176 - 84 0910-8327 2016/07 [Refereed]
    Bepridil is an effective antiarrhythmic drug on supraventricular and ventricular arrhythmias, and inhibitor of calmodulin. Recent investigations have been elucidating that bepridil exerts antiarrhythmic effects through its acute and chronic application for patients. The aim of this study was to identify the efficacy and the potential mechanism of bepridil on the inward-rectifier potassium channel in neonatal rat cardiomyocytes in acute- and long-term conditions. Bepridil inhibited inward-rectifier potassium current (I K1) as a short-term effect with IC50 of 17 μM. Bepridil also reduced I K1 of neonatal cardiomyocytes when applied for 24 h in the culture medium with IC50 of 2.7 μM. Both a calmodulin inhibitor (W-7) and an inhibitor of calmodulin-kinase II (KN93) reduced I K1 when applied for 24 h as a long-term effect in the same fashion, suggesting that the long-term application of bepridil inhibits I K1 more potently than that of the short-term application through the inhibition of calmodulin kinase II pathway in cardiomyocytes.
  • Masaki Morishima; Eriko Iwata; Chisato Nakada; Yoshiyuki Tsukamoto; Hiroki Takanari; Shinji Miyamoto; Masatsugu Moriyama; Katsushige Ono
    Circulation journal : official journal of the Japanese Circulation Society JAPANESE CIRCULATION SOC 80 (6) 1346 - 55 1346-9843 2016/05 [Refereed]
    BACKGROUND: Atrial fibrillation (AF) begets AF in part due to atrial remodeling, the molecular mechanisms of which have not been completely elucidated. This study was conducted to identify microRNA(s) responsible for electrical remodeling in AF. METHODS AND RESULTS: The expression profiles of 1205 microRNAs, in cardiomyocytes from patients with persistent AF and from age-, gender-, and cardiac function-matched control patients with normal sinus rhythm, were examined by use of a microRNA microarray platform. Thirty-nine microRNAs differentially expressed in AF patients' atria were identified, including miR-30d, as a candidate responsible for ion channel remodeling by in silico analysis. MiR-30d was significantly upregulated in cardiomyocytes from AF patients, whereas the mRNA and protein levels ofCACNA1C/Cav1.2 andKCNJ3/Kir3.1, postulated targets of miR-30d, were markedly reduced.KCNJ3/Kir3.1 expression was downregulated by transfection of the miR-30 precursor, concomitant with a reduction of the acetylcholine-sensitive inward-rectifier K(+)current (IK.ACh).KCNJ3/Kir3.1 (but notCACNA1C/Cav1.2) expression was enhanced by the knockdown of miR-30d. The Ca(2+)ionophore, A23187, induced a dose-dependent upregulation of miR-30d, followed by the suppression ofKCNJ3mRNA expression. Blockade of protein kinase C signaling blunted the [Ca(2+)]i-dependent downregulation of Kir3.1 via miR-30d. CONCLUSIONS: The downward remodeling ofIK.AChis attributed, at least in part, to deranged Ca(2+)handling, leading to the upregulation of miR-30d in human AF, revealing a novel post-transcriptional regulation ofIK.ACh. (Circ J 2016; 80: 1346-1355).
  • Toru Shimaoka; Yan Wang; Masaki Morishima; Shinji Miyamoto; Katsushige Ono
    Pathophysiology : the official journal of the International Society for Pathophysiology 22 (2) 87 - 93 0928-4680 2015/06 [Refereed]
    The present study was designed to investigate the effect of magnesium (Mg) depletion on the expression of voltage-gated calcium (Ca(2+)) channels and Ca(2+) currents in the heart and thereby on hypomagnesemic arrhythmogenesis in adult male rats. Male Wistar rats were fed an Mg-free diet or a normal diet for up to 16 weeks. Serum Mg concentrations were significantly reduced at week 4 or later with an Mg-free diet, which experimentally represents hypomagnesemia. Myocardial Mg contents were also reduced at week 16 accompanied by myocardial hypertrophy. Telemetric ECG recordings revealed a long-term changes of ECG parameters in hypomagnesemic rats; RR shortening, QT prolongation and appreciable PR prolongation. At the same time, hypomagnesemic rats demonstrate various bradycardiac arrhythmias including ventricular premature beats, atrioventricular blocks and sinus arrest, which were never recoded in rats fed by a normal diet. Electrophysiological studies elucidated that the L-type Ca(2+) channel current was decreased in Mg-deficient cardiomyocytes, and these findings were consistent with down-regulation of CaV1.2-mRNA but not in levels of CaV1.3, CaV3.1 or CaV3.2. These findings provide novel insights into hypomagnesemic electrophysiological disorders in the heart, and should be considered when assessing the design of effective antiarrhythmic treatments in patients with hypomagnesemia.
  • Takamasa Ohnishi; Fumiko Hisaoka; Masaki Morishima; Akira Takahashi; Nagakatsu Harada; Kazuaki Mawatari; Hidekazu Arai; Emiko Yoshioka; Satomi Toda; Izumi Keisuke; Yutaka Nakaya
    Journal of toxicologic pathology JAPANESE SOC TOXICOLOGIC PATHOLOGY 27 (1) 51 - 6 0914-9198 2014/04 [Refereed]
    Studies that investigate the underlying mechanisms of disease and treatment options typically require the use of a suitable animal model. Few suitable animal models exist for left atrial thrombosis. Here, we demonstrated that the Spontaneously-Running-Tokushima-Shikoku (SPORTS) rat - a Wistar strain known for its running ability-is predisposed to the development of thrombi in the left atrium. We investigated the incidence of left atrial thrombosis in male (n = 16) and female (n = 17) SPORTS rats and observed organized atrial thrombosis in 57% and 38% of males and female rats, respectively. In the male rats, systolic blood pressures and heart rates were significantly higher in SPORTS rats than in control Wistar rats. We could not find any evidence of arrhythmias, such as atrial fibrillation, during electrocardiographic examination of SPORTS rats. We believe that the SPORTS rat could serve as a new research model for left atrial thrombosis; further, it may be suitable for research investigating the development of new antithrombotic approaches for the control of atrial thrombosis or familial thrombophilia in humans.
  • Kazuaki Mawatari; Emiko Yoshioka; Satomi Toda; Sonoko Yasui; Hiroko Furukawa; Takaaki Shimohata; Takamasa Ohnishi; Masaki Morishima; Nagakatsu Harada; Akira Takahashi; Hiroshi Sakaue; Yutaka Nakaya
    Circulation journal : official journal of the Japanese Circulation Society JAPANESE CIRCULATION SOC 78 (8) 1980 - 8 1346-9843 2014 [Refereed]
    BACKGROUND: Left atrial (LA) thrombosis is an important cause of systemic embolization. The SPORTS rat model of LA thrombi (Spontaneously-Running Tokushima-Shikoku), which have a unique characteristic of high voluntary wheel running, was previously established. The aim of the present study was to investigate how SPORTS rats develop LA thrombi. METHODS AND RESULTS: Nitric oxide (NO) produced from cardiovascular endothelial cells plays an important protective role in the local regulation of blood flow, vascular tone, and platelet aggregation. No evidence of atrial fibrillation or hypercoagulability in SPORTS rats regardless of age was found; however, SPORTS rats demonstrated endothelial dysfunction and a decrease of NO production from a young age. In addition, endothelial NO synthase activity was significantly decreased in the LA and thoracic aorta endothelia of SPORTS rats. While voluntary wheel running was able to intermittently increase NO levels, running did not statistically decrease the incidence of LA thrombi at autopsy. However, L-arginine treatment significantly increased NO production and provided protection from the development of LA thrombi in SPORTS rats. CONCLUSIONS: They present study results indicate that NO has an important role in the development of LA thrombus, and endothelia pathways could provide new targets of therapy to prevent LA thrombosis.
  • Masaki Morishima; Shintaro Tahara; Yan Wang; Toshihiko Kaku; Katsushige Ono
    Journal of Arrhythmia 26 (2) 111 - 118 1880-4276 2010 [Refereed]
    Background: The neurohypophyseal hormones oxytocin (OT) and [Arg8]-vasopressin (AVP) have recently been implicated in cardiac function. This study was designed to investigate actions of OT and AVP on regulation of the voltage-gated Ca2+ channel in cardiomyocytes. Methods and Results: Cultured neonatal rat cardiomyocytes were stimulated with OT or AVP (10~8 M to 10~6 M) for 24-72 h, followed by real-time PCR and patch clamp studies. Although OT did not exert any modulatory effect on L-type Ca2+ channel current, as a short-term effect, stimulation of cardiomyocytes with OT but not AVP decreased the expression of CaV1.2 mRNA with a reduced L-type Ca2+ channel current. A transcription factor CREB mRNA expression was down-regulated by OT treatment, although T-type Ca2+ channels (CaV3.1, CaV3.2) were unaffected by OT or AVP. Conclusion: OT but not AVP down-regulates L-type Ca2+ channel expression through the inhibition of CREB transcriptional, suggesting a novel mechanism of OT action in the cardiac electrophysiology. © 2010, Japanese Heart Rhythm Society. All rights reserved.
  • Atsushi Hattori; Kazuaki Mawatari; Satomi Tsuzuki; Emiko Yoshioka; Satomi Toda; Masaki Yoshida; Sonoko Yasui; Hiroko Furukawa; Masaki Morishima; Katsushige Ono; Takamasa Ohnishi; Masayuki Nakano; Nagakatsu Harada; Akira Takahashi; Yutaka Nakaya
    Obesity (Silver Spring, Md.) 18 (1) 48 - 54 1930-7381 2010/01 [Refereed]
    We established a new animal model called SPORTS (Spontaneously-Running Tokushima-Shikoku) rats, which show high-epinephrine (Epi) levels. Recent reports show that Epi activates adenosine monophosphate (AMP)-activated protein kinase (AMPK) in adipocytes. Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in fatty acid synthesis, and the enzymatic activity is suppressed when its Ser-79 is phosphorylated by AMPK. The aim of this study was to investigate the in vivo effect of Epi on ACC and abdominal visceral fat accumulation. We divided both 6-week male control and SPORTS rats into two groups, which were fed either normal diet or high fat and sucrose (HFS) diet for 16 weeks. At the end of diet treatment, retroperitoneal fat was collected for western blotting and histological analysis. Food intake was not different among the groups, but SPORTS rats showed significantly lower weight gain than control rats in both diet groups. After 10 weeks of diet treatment, glucose tolerance tests (GTTs) revealed that SPORTS rats had increased insulin sensitivity. Furthermore, SPORTS rats had lower quantities of both abdominal fat and plasma triglyceride (TG). In abdominal fat, elevated ACC Ser-79 phosphorylation was observed in SPORTS rats and suppressed by an antagonist of beta-adrenergic receptor (AR), propranolol, or an inhibitor of AMPK, Compound C. From these results, high level of Epi induced ACC phosphorylation mediated through beta-AR and AMPK signaling pathways in abdominal visceral fat of SPORTS rats, which may contribute to reduce abdominal visceral fat accumulation and increase insulin sensitivity. Our results suggest that beta-AR-regulated ACC activity would be a target for treating lifestyle-related diseases, such as obesity.
  • L. Kang; M. Q. Zheng; M. Morishima; Y. Wang; T. Kaku; K. Ono
    British Journal of Pharmacology WILEY-BLACKWELL 157 (3) 404 - 414 0007-1188 2009/06 [Refereed]
    Background and purpose: Bepridil is an anti-arrhythmic agent with anti-electrical remodelling effects that target many cardiac ion channels, including the voltage-gated Na + channel. However, long-term effects of bepridil on the Na - channel remain unclear. We explored the long-term effect of bepridil on the Na + channel in isolated neonatal rat cardiomyocytes and in a heterologous expression system of human Na v1.5 channel. Experimental approach: Na + currents were recorded by whole-cell voltage-clamp technique. Na + channel message and protein were evaluated by real-time RT-PCR and Western blot analysis. Key results: Treatment of cardiomyocytes with 10 μmol-L -1 bepridil for 24 h augmented Na + channel current (/ Na) in a dose- and time-dependent manner. This long-term effect of bepridil was mimicked or masked by application of W-7, a calmodulin inhibitor, but not KN93 [2-[N-(2- hydroxyethyl)-N-(4-methoxy benzenesulphonyl)]-amino-N-(4-chlorocinnamyl)N- methylbenzylamine], a Ca 2+/calmodulin-dependent kinase inhibitor. During inhibition of protein synthesis by cycloheximide, the / Na increase due to bepridil was larger than the increase without cycloheximide. Bepridil and W-7 significantly slowed the time course of Na v1.5 protein degradation in neonatal cardiomyocytes, although the mRNA levels of Nav1.5 were not modified. Bepridil and W-7 did not increase / Na any further in the presence of the proteasome inhibitor MGI32 [N[(phenylmethoxy) carbonyl]-L-leucyl-N-[(1S)-1-formyl-3-methylbutyl]-L-leucinamide]. Bepridil, W-7 and MC132 but not KN93 significantly decreased 20S proteasome activity in a concentration-dependent manner. Conclusions and implications: We conclude that long-term exposure of cardiomyocytes to bepridil at therapeutic concentrations inhibits calmodulin action, which decreased degradation of the Na v1.5 a-subunit, which in turn increased Na + current. © 2009 The British Pharmacological Society All rights reserved.
  • Masaki Morishima; Yan Wang; Yuko Akiyoshi; Shinji Miyamoto; Katsushige Ono
    European journal of pharmacology ELSEVIER 609 (1-3) 105 - 12 0014-2999 2009/05 [Refereed]
    Recently, it has been revealed that angiotensin II type 1 receptor (AT(1)) antagonists act as antiarrhythmic agents and that the T-type Ca2+ channel plays an important role in arrhythmia. However, it remains unclear how the T-type Ca2+ channel expression system is involved in angiotensin II-mediated arrhythmogenesis in cardiomyocytes. In this study, we investigated the effect of telmisartan, an AT(1) receptor antagonist, on transcriptional regulation of T-type Ca2+ channel isoform (Ca(v)3.1 and Ca(v)3.2) expression and cardiac contractility using rat neonatal cardiomyocytes. Cultured cardiomyocytes were stimulated with telmisartan and/or angiotensin II for 24 h. T-type Ca2+ currents (I(Ca.T)) were then measured with the patch clamp technique, while Ca(v)3.1 and Ca(v)3.2 mRNA expression were assessed by real-time PCR. Expression of Ca(v)3.1 and Ca(v)3.2 mRNA as well as I(Ca.T) current density in cardiomyocytes increased significantly after long-term application of angiotensin II (24 h), which was accompanied by extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation. In contrast, telmisartan decreased Ca(v)3.1 and Ca(v)3.2 mRNA expression as well as I(Ca.T) in a dose-dependent manner in the absence of angiotensin II. In addition, the basal phosphorylation level of p38MAPK but not ERK1/2 was decreased by telmisartan in the absence of angiotensin II. Valsartan, an AT(1) receptor antagonist, did not mimic the action of telmisartan, while the action of telmisartan was completely blocked by valsartan. These results indicate that telmisartan attenuates T-type Ca2+ channel expression likely through p38MAPK activity in an agonist-independent manner, which suggests a novel pharmacological action of telmisartan.
  • Farzana Marni; Yan Wang; Masaki Morishima; Toru Shimaoka; Tomoko Uchino; Mingqi Zheng; Toshihiko Kaku; Katsushige Ono
    Endocrinology ENDOCRINE SOC 150 (2) 879 - 88 0013-7227 2009/02 [Refereed]
    T-type Ca(2+) channel current (I(Ca,T)) plays an important role for spontaneous pacemaker activity and is involved in the progression of structural heart diseases. Estrogens are of importance for the regulation of growth and differentiation and function in a wide array of target tissues, including those in the cardiovascular system. The aim of this study was to elucidate the short-term and long-term effects of 17beta-estradiol (E(2)) on I(Ca,T) in cardiomyocytes. We employed in vivo and in vitro techniques to clarify E(2)-mediated modulation of heart rate (HR) in ovariectomized rats and I(Ca,T) in cardiomyocytes. Ovariectomy increased HR and E(2) supplement reduced HR in ovariectomized rats. Slowing of E(2)-induced HR was consistent with the deceleration of automaticity in E(2)-treated neonatal cardiomyocytes. Short-term application of E(2) did not have significant effects on I(Ca,T), whereas in cardiomyocytes treated with 10 nm E(2) for 24 h, estrogen receptor-independent down-regulation of peak I(Ca,T) and declination of Ca(V)3.2 mRNA were observed. Expression of a cardiac-specific transcription factor Csx/Nkx2.5 was also suppressed by E(2) treatment for 24 h. On the other hand, expression of Ca(V)3.1 mRNA was unaltered by E(2) treatment in this study. An ERK-1/2, 5 inhibitor, PD-98059, abolished the effects of E(2) on I(Ca,T) and Ca(V)3.2 mRNA as well as Csx/Nkx2.5 mRNA. These findings indicate that E(2) decreases Ca(V)3.2 I(Ca,T) through activation of ERK-1/2, 5, which is mediated by the suppression of Csx/Nkx2.5-dependent transcription, suggesting a genomic effect of E(2) as a negative chronotropic factor in the heart.
  • Yan Wang; Masaki Morishima; Mingqi Zheng; Tomoko Uchino; Kazuaki Mannen; Akira Takahashi; Yutaka Nakaya; Issei Komuro; Katsushige Ono
    Journal of molecular and cellular cardiology ELSEVIER SCI LTD 42 (6) 1045 - 53 0022-2828 2007/06 [Refereed]
    The cardiac transcription factors Csx/Nkx2.5 and GATA4 play important roles in vertebrate heart development. Although mutations of Csx/Nkx2.5 or GATA4 are associated with various congenital heart diseases, their mechanism of action on cardiomyocyte function is not completely elucidated. In this study, we therefore investigated the actions of these transcription factors on the electrophysiological features and expression of ion channels in cardiomyocytes. Genes for transcription factors Csx/Nkx2.5 and GATA4 were transfected into rat neonatal cardiomyocytes by adenoviral infection. Action potentials, L-, T-type Ca(2+) channels and hyperpolarization-activated cation current (I(h)) of rat neonatal myocytes were recorded by patch clamp technique after adenoviral infection. Expression of ion channels was confirmed by real-time PCR. In Csx/Nkx2.5 overexpression myocytes, the spontaneous beating rate was markedly increased with an up-regulation of the Ca(v)3.2 T-type Ca(2+) channel, while in GATA4 overexpression myocytes, the T-type Ca(2+) channel was unchanged. On the other hand, the L-type Ca(2+) channel was down-regulated by both Csx/Nkx2.5 and GATA4 overexpression; the level of Ca(v)1.3 mRNA was dramatically decreased by Csx/Nkx2.5 overexpression. These results indicate that Csx/Nkx2.5 and GATA4 play important roles on the generation of pacemaker potentials modulating voltage-dependent Ca(2+) channels in the neonatal cardiomyocyte.
  • Nagakatsu Harada; Akiko Kusuyama; Masaki Morishima; Kazuko Okada; Akira Takahashi; Yutaka Nakaya
    Metabolism: clinical and experimental W B SAUNDERS CO-ELSEVIER INC 56 (4) 517 - 22 0026-0495 2007/04 [Refereed]
    Bacterial endotoxin/lipopolysaccharide (LPS)-induced cachexia is characterized by weight loss, anorexia, and a disturbance in lipid metabolism, namely, hypertriacylglycerolemia. The aim of this study in rats with acute endotoxicity induced by an injection of LPS was to investigate whether bezafibrate, a ligand for peroxisome proliferator-activated receptor alpha and a lipoprotein lipase (LPL) activator, improved cachectic conditions, including impaired lipid metabolism. Short-term administration of LPS in the rats resulted in impairment of triacylglycerol clearance in plasma after the intake of fresh cream. In addition, LPS increased whole-body energy expenditure, reduced fasting body weight and caused anorexia in the rats. Bezafibrate treatment resulted in significant improvements in LPS-induced dyslipidemia and anorexia, but had no effect on energy expenditure, respiratory quotient, or fasting body weight in the endotoxic rats. Administration of LPS was also associated with a decrease in the level of messenger RNA (mRNA) expression for LPL in white adipose tissue and skeletal muscle and an increase in the mRNA levels for uncoupling protein 3 in skeletal muscle. Bezafibrate treatment reversed the decline in LPL mRNA levels in white adipose tissue but not in the skeletal muscle tissue of the rats. The enhanced uncoupling protein 3 mRNA level in the endotoxic rats was not affected by bezafibrate treatment. Plasma concentration of leptin was increased by short-term LPS treatment. Bezafibrate decreased the level of plasma leptin significantly without affecting the level of leptin mRNA expression. These results suggest that bezafibrate may be an effective drug not only for impaired triacylglycerol metabolism, but also for anorexia in cachectic states induced by bacterial infections.
  • Masaki Morishima; Nagakatsu Harada; Sayuri Hara; Atsuko Sano; Hiromasa Seno; Akira Takahashi; Yusuke Morita; Yutaka Nakaya
    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology NATURE PUBLISHING GROUP 31 (12) 2627 - 38 0893-133X 2006/12 [Refereed]
    An understanding of neurological mechanisms for wheel running by rodents, especially with high exercise activity, would be applicable to a strategy for promotion of exercise motivation in humans. One of several brain regions that are candidates for the regulation of physical exercise is the hippocampus. Here we examined the running activity of Spontaneously-Running-Tokushima-Shikoku (SPORTS) rat, a new animal model for high levels of wheel-running activity, and its relation with the hippocampal norepinephrine (NE) system including the levels of NE, adrenergic receptors, and degradation enzymes for monoamines. In the hippocampus of SPORTS rats, the level of NE in extracellular fluid was augmented, whereas the level in the homogenate of the whole tissue was decreased even for sedentary conditions. Elevated extracellular NE caused downregulation of alpha(2)-adrenergic receptors in the hippocampus of SPORTS rats. Local administration of alpha(2)-adrenergic receptor antagonist yohimbine, but not of alpha(2)-agonist clonidine, into the hippocampus suppressed high running activity in SPORTS rats. The protein expression and the activity levels of monoamine oxidase A (MAOA), a critical enzyme for the degradation of NE, were decreased in the hippocampus of SPORTS rats to increase extracellular NE level. Thus, inhibition of oxidase activity in normal Wistar rats markedly increased wheel-running activity. These results indicate that decreased MAOA activity, elevation of extracellular NE, and alpha(2)-adrenergic receptors in the hippocampus determine the neural basis of the psychological regulation of exercise behavior in SPORTS rats.
  • Sachiko Chikahisa; Hiroyoshi Sei; Masaki Morishima; Atsuko Sano; Kazuyoshi Kitaoka; Yutaka Nakaya; Yusuke Morita
    Behavioural brain research ELSEVIER SCIENCE BV 169 (2) 312 - 9 0166-4328 2006/05 [Refereed]
    Music has been suggested to have a beneficial effect on various types of performance in humans. However, the physiological and molecular mechanism of this effect remains unclear. We examined the effect of music exposure during the perinatal period on learning behavior in adult mice, and measured the levels of brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), which play critical roles in synaptic plasticity. In addition, we measured the levels of 3-phosphoinositide-dependent protein kinase-1 (PDK1) and mitogen-activated protein kinase (MAPK), downstream targets of two main pathways in BDNF/TrkB signaling. Music-exposed mice completed a maze learning task with fewer errors than the white noise-exposed mice and had lower levels of BDNF and higher levels of TrkB and PDK1 in the cortex. MAPK levels were unchanged. Furthermore, TrkB and PDK1 protein levels in the cortex showed a significant negative correlation with the number of errors on the maze. These results suggest that perinatal exposure of mice to music has an influence on BDNF/TrkB signaling and its intracellular signaling pathway targets, including PDK1, and thus may induce improved learning and memory functions.
  • Yutaka Nakaya; Masaki Morishima-Yamato; Kaori Ishida; Nagakatsu Harada; Masayuki Nakano
    Journal of Medical Investigation 52 (SUPPL.) 244  1343-1420 2005/11 [Refereed]
    A stress-resistant rat model was introduced. SPORTS (Spontaneously-Running- Tokushima-Shikoku) rats showed significantly shorter time of immobility in the forced swim test compared to control Wister rats. Increase norepinephrine concentration secondary to decreased activity of monoamine oxidase A (MAOA) in hippocampus was observed in this model rats. This model rats are considered to be useful for studying the mechanism of psychological stress.
  • Masaki Morishima-Yamato; Fumiko Hisaoka; Sachiko Shinomiya; Nagakatsu Harada; Hideki Matoba; Akira Takahashi; Yutaka Nakaya
    Life Sciences PERGAMON-ELSEVIER SCIENCE LTD 77 (5) 551 - 561 0024-3205 2005/06 [Refereed]
    We generated an original Wistar line of rats that displayed increased levels of wheel running, which we named SPORTS (Spontaneously-Running-Tokushima- Shikoku). Male SPORTS rats ran voluntarily in a running wheel almost six times longer than male control Wistar rats, established without selection for their running activity. The running phenotype of female SPORTS rats was the same as female control Wistar rats. However, male offspring from the cross-mating between a female SPORTS rat and a male control rat also showed a similar level of hyper-running activity as the original SPORTS line. Compared to control rats, male SPORTS rats had lower levels of mean body weight, abdominal fat and plasma insulin after 4 weeks of running. It is likely that all these beneficial changes observed in the SPORTS rats reflected the increases in glucose disposal we observed in oral glucose tolerance tests carried out on the animals. We also found hyper-running caused a significant increase in skeletal muscle oxidative capacity, measured as the ratio of malate dehydrogenase to phosphofructokinase activity, an index of aerobic metabolism. These results indicate that the SPORTS rat may be a good animal model for determining the mechanisms responsible for up-regulation of running motivation, in addition to investigating changes in nutrient metabolism induced by high intensity exercise. © 2005 Elsevier Inc. All rights reserved.
  • Nagakatsu Harada; Chika Ninomiya; Yoshie Osako; Masaki Morishima; Kazuaki Mawatari; Akira Takahashi; Yutaka Nakaya
    Obesity research NORTH AMER ASSOC STUDY OBESITY 12 (7) 1077 - 84 1071-7323 2004/07 [Refereed]
    OBJECTIVE: To assess the effect of taurine supplementation on respiratory gas exchange, which might reflect the improved metabolism of glucose and/or lipid in the type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. RESEARCH METHODS AND PROCEDURES: Male OLETF rats (16 weeks of age) were randomly divided into two groups: unsupplemented group and taurine-supplemented (3% in drinking water) group. After 9 weeks of treatment, indirect calorimetry and insulin tolerance tests were conducted. The amounts of visceral fat pads, tissue glycogen, the blood concentrations of glucose, triacylglycerol, taurine, and electrolytes, and the level of hematocrit were compared between groups. A nondiabetic rat strain (Long-Evans Tokushima Otsuka) was used as the age-matched normal control. RESULTS: The indirect calorimetry showed that the treatment of OLETF rats with taurine could reduce a part of postprandial glucose oxidation possibly responsible for the increase of triacylglycerol synthesis in the body. Taurine supplementation also improved hyperglycemia and insulin resistance and increased muscle glycogen content in the OLETF rats. Supplementation with taurine increased the blood concentration of taurine and electrolyte and fluid volume, all of which were considered to be related to the improvement of metabolic disturbance in OLETF rats. DISCUSSION: Taurine supplementation may be an effective treatment for glucose intolerance and fat/lipid accumulation observed in type 2 diabetes associated with obesity. These metabolic changes might be ascribed, in part, to the alteration of circulating blood profiles, where the improved hyperglycemia and/or the blood accumulation of taurine itself would play roles.
  • Eiko Takishita; Akira Takahashi; Nagakatsu Harada; Masaki Yamato; Masaki Yamato; Yutaka Nakaya
    Journal of Cardiovascular Pharmacology LIPPINCOTT WILLIAMS & WILKINS 43 (2) 266 - 270 0160-2446 2004/02 [Refereed]
    5-hydroxytryptamine (5-HT) is closely related to pathogenesis of angiopathy in type 2 diabetes. Acute and chronic effects of sarpogrelate hydrochloride (sarpogrelate), a 5-HT2 blocker, on glucose tolerance and insulin resistance were examined. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes, were randomly assigned to 2 groups; those with 30 mg/kg BW/d sarpogrelate treatment of 4 weeks (HTB group) and without (control group). The glucose infusion rate was significantly increased in the HTB group compared with the control group. The blood glucose levels after oral glucose tolerance test and levels of plasma insulin and lipids were significantly lower in the HTB group than in the control group. To investigate mechanism of the improvement by sarpogrelate, acute effect of 5-HT and its blocking effect by sarpogrelate on blood levels of glucose were examined in 25-week-old Sprague-Dawley rats. Blood glucose levels were significantly increased by administration of 5-HT. This increase was reversed by pretreatment of sarpogrelate. A plasma adrenaline level also rose significantly by injection of the 5-HT and was prevented by pretreatment of sarpogrelate. These results indicate that sarpogrelate improves insulin resistance in type 2 diabetic rats.
  • Sachinobu Manabe; Ikuyo Kurroda; Kazuko Okada; Masaki Morishima; Miki Okamoto; Nagakatsu Harada; Akira Takahashi; Kentaro Sakai; Yutaka Nakaya
    Journal of nutritional science and vitaminology CENTER ACADEMIC PUBL JAPAN 49 (6) 375 - 80 0301-4800 2003/12 [Refereed]
    Taurine is reported to increase contractility of skeletal muscle and cardiac myocyte, which can increase exercise performance. The present study aimed to clarify taurine's effect on chronic endurance exercise, especially accumulation of lactic acid (LA), a marker of fatigue and ability of aerobic exercise, and urinary secretion of 3-methylhistidine (3-MH), a marker of muscle breakdown in rats. After exercise blood levels of LA and urinary excretion of 3-MH were significantly increased and this increase was significantly less in those with chronic treatment of taurine. Taurine treatment also significantly decreased fat accumulation and blood levels of cholesterol and triglyceride, which might improve insulin resistance and utilization of fat and glucose. These results indicate taurine treatment is useful for reducing physical fatigue and muscle damage during exercise training in rats, presumably due to antioxidant property and improvement of muscle and cardiac functions by taurine.

Conference Activities & Talks

  • Utilization of non-standard products and development of health promotion  [Invited]
    Masaki Morishima
    Furikake: Healthy Savory Sprinkles  2023/11
  • おいしさの「見える化」ー食品の官能検査ー
    令和5年後第67回農業実験実習講習会(近畿大学附属湯浅農場)  2023/07
  • 人と地球の健康を目指した食環境整備  [Invited]
    森島 真幸
    近畿大学x神戸大学SDGsフォーラム 「食の循環」~大阪湾を囲んだ二つの大学、初のアクション~  2023/07
  • The effects of omega-3 polyunsaturated fatty acids on cardiac rhythm and electrical excitability  [Invited]
    Masaki Morishima
    第69回日本不整脈心電学会学術大会 心電学サミット  2023/07
  • 「近大ふりかけ」で自然と健康になれる食環境の実現へ
    森島 真幸
    近畿大学農学部公開講座2023  2023/05
  • Polyunsaturated fatty acids and cardiovascular health  [Invited]
    Masaki Morishima
    The 100th Anniversary Annual Meeting of The Physiological Society of Japan  2023/03
  • コロナ禍に負けない身体づくりと食環境整備  [Invited]
    森島 真幸
    はりま産学交流会  2022/10
  • 未利用食材の活用によるポストコロナ時代の食環境整備  [Invited]
    森島 真幸
    近畿大学研究シーズ発表会  2022/09


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Awards & Honors

  • 2023/08 第32回日本病態生理学会大会 学部学生・修士課程大学院生セッション 優秀賞
    受賞者: 鈴木巴乃;ZHU MOHAN;堀井鴻佑;森島真幸
  • 2022/08 日本病態生理学会 学部学生・修士課程大学院生セッション 優秀賞
    受賞者: 松永華奈;山本こはる;堀井鴻佑;森島真幸
  • 2021/03 日本循環器学会 Circulation Journal誌 年間優秀論文賞(Experimental Investigation)
    受賞者: 嶋岡徹*、王岩*、森島真幸*、宮本伸二、小野克重
  • 2014/07 日本不整脈心電学会 第29回日本不整脈学会学術大会・第31回日本心電学会学術集会合同学術大会 Young Investigator's Award
    受賞者: 森島 真幸
  • 2013/08 日本病態生理学会 第23回日本病態生理学会大会 特別表彰
    受賞者: 森島 真幸
  • 2013/07 第12回九州脳・高血圧・循環制御研究会 最優秀演題賞
    受賞者: 森島 真幸
  • 2008/07 第7回九州脳と高血圧研究会 最優秀賞
    受賞者: 森島 真幸
  • 2007/11 日本心臓財団 第5回日本心臓財団若年研究者研究奨励(藤基金)
    受賞者: 森島 真幸
  • 2007/06 International Society for Heart Research Young Investigator's Award
    受賞者: Masaki Morishima
  • 2006/02 徳島大学 康楽賞
    受賞者: 森島 真幸
  • 2005/08 徳島大学, 徳島県医師会 第232回徳島医学会 最優秀演題賞
    受賞者: 森島 真幸

Research Grants & Projects

  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    Date (from‐to) : 2023/04 -2026/03 
    Author : 森島 真幸
  • 日本学術振興会:科学研究費助成事業 基盤研究(C)
    Date (from‐to) : 2020/04 -2023/03 
    Author : 森島 真幸
  • microRNA過剰発現ラットの作製とそれを用いた新しい不整脈発症機序の解明
    日本学術振興会:平成27年度科学研究費助成事業 国際共同研究加速基金
    Date (from‐to) : 2016/04 -2019/03 
    Author : 森島 真幸
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2015/04 -2018/03 
    Author : MORISHIMA Masaki
    We have previously shown that miR-30d is up-regulated in cardiomyocytes with persistent atrial fibrillation (AF), in response to cellular Ca2+-overload. It is well-known that abnormal Ca2+ dynamics may lead to the development of AF, however, mechanisms for microRNA-30d (miR-30d) up-regulation in AF cardiomyocytes have not been elucidated. To investigate whether Ca2+ overload regulates miR-30d expression in adult or neonatal rat cardiomyocytes, we infused angiotensin II (Ang II; 1.68 mg/kg/day) or noradrenaline (NA; 5.4 mg/kg/day) for 2 weeks via osmotic minipump into adult Wistar rats, because Ang II and NA are well-known drivers for onset of AF. Acute- or long-term stimulation of cardiomyocytes by Ang II induces elevation of miR-30d expression independently of the changes in blood pressure. The correlation of miR-30d expression between plasma and atrium was positively indicated. Our data would propose circulating miRNA-30d as promise biomarkers and therapeutic targets in AF.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Fund for the Promotion of Joint International Research (Fostering Joint International Research)
    Date (from‐to) : 2016 -2018 
    Author : MORISHIMA Masaki; Singh Harpreet
    Our previous study has shown that microRNA-30d(miR-30d) is up-regulated in cardiomyocytes with persistent atrial fibrillation (AF), in response to cellular Ca2+-overload. However, mechanisms for miR-30d up-regulation in AF cardiomyocytes have not been elucidated. In this study, we investigated the mechanism how microRNA-30d (miR-30d) involved in the development of AF pathogenesis, we established a novel cardio-specific miR-30d overexpressed rat. MiR-30d overexpressed rats showed more vulnerable and short life span compared with wild type rats. The correlation of miR-30d expression between plasma and atrium was positively indicated in those rats. These data proposed circulating miRNA-30d as promise biomarkers and therapeutic targets in AF.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    Date (from‐to) : 2012/04 -2015/03 
    Author : MORISHIMA Masaki
    We established a new animal model called SPORTS rats. The aim of this study was to investigate the role of the L-type Ca2+ channel in cardiomyocytes and its relation with intracellular Ca2+-dependent signalings in cardiac adaptation responding to high physical activity. Injection of Ca2+ channel antagonist verapamil markedly decreased wheel-running activity with a reduction of heart rate in SPORTS rats. In isolated neonatal rat cardiomyocytes from SPORTS rats, spontaneous beating rate, L-type Ca2+ current, and the expression ofits mRNAs were significantly higher than those in control rat. Phosphorylation of CREB and Akt were significantly elevated in SPORTS rat myocytes in the basal condition. These results suggest that phosphorylation of the CREB via activation of PI3K/Akt signaling pathway in SPORTS rats positively regulates the L-type Ca2+ channel expression, which is responsible for the enhancement of physiological hypertrophy and chronotropy in the heart.
  • 運動意欲促進の分子メカニズムの解明
    日本学術振興会:平成21年度科学研究費補助金 若手研究(B)
    Date (from‐to) : 2009/04 -2012/03 
    Author : 森島 真幸
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2010 -2012 
    Author : IWATA Eriko; ONO Katishige; MORISHIMA Masaki
    Even though atrial fibrillation is the most commonly encountered clinical arrhythmia,the therapeutic strategy has not been established. Atrial tissue was obtained from patients undergoing cardiovascular surgery using extracorporial circulation. W e identified some ion channels and microRNAs that were down-regulated or up-regulated in atrial fibrillation patients, and suggested it’ s relation to ion channel remodeling and the possibility of therapeutic application.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)
    Date (from‐to) : 2009 -2011 
    Author : MORISHIMA Masaki; NAKAYA Yutaka
    We established a novel rat strain featured by high levels of voluntary wheel-running, which is called SPORTS(Spontaneously-Running Tokushima-Shikoku) rat. The aim of this study was to investigate the effect of high-or low-intensities in voluntary exercise on sympathetic and vagal controls of heart at sedentary and during wheel-running exercise by use of SPORTS rats. At 15 weeks of age, each rat was moved to a new cage with or without an exercise wheel, and sorted into four groups ; 1) SPORTS rat with an exercise wheel(running), 2) SPORTS rat without an exercise wheel(sedentary), 3) control rat with an exercise wheel(running), and 4) control rat without an exercise wheel(sedentary). Heart rate was significantly increased in sedentary SPORTS rats compared to those in control rats. SPORTS rats show a significant reduction in resting heart rate by high-intensity running. The low frequency/high frequency(LF/HF) ratio, which reflects cardiac sympathetic nerve activity, was significantly decreased in SPORTS rats by voluntary running. However, a decrease of sympathetic nerve activity was not observed in control rats with approximately 1/10 wheel-running activity. By wheel running, the low frequency(LF) power was augmented in control rats, and was markedly depressed in SPORTS rats. High-intensity voluntary running decreases mean heart rate during resting period(sedentary) with a depression of sympathetic nerve activity. These results suggest that high-intensity voluntary exercise attenuates sympathetic nerve activity not only during exercise but also during resting period as a lasting effects.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2007 -2008 
    Author : ONO Katsushige; ONO Katsushige; LEE Tae-seong; ZENG Ming-qi; MORISHIMA Masaki
  • アンジオテンシンII受容体を介する心筋イオンチャネルremodelingの分子機序の解明
    Author : 森島 真幸

Teaching Experience

  • Functional food scienceFunctional food science Kindai University
  • Functional food scienceFunctional food science Kindai University
  • public health nutritionpublic health nutrition Kindai University

Social Contribution

  • コロナ禍がもたらした健康への新たなアプローチ ~身近な食材に存在する天然酵母を観察してみよう~
    Date (from-to) : 2022/10/28
    Role : Appearance
    Category : Visiting lecture
    Sponser, Organizer, Publisher  : 近畿大学農学部
    Event, Program, Title : 近畿大学農学部キャンパス見学会(附属東広島中学校)
  • キャンパス発この一品「未利用食材活用のふりかけ―近畿大」
    Date (from-to) : 2022/03/16
    Role : Appearance
    Category : Paper
    Sponser, Organizer, Publisher  : 日本経済新聞
    Event, Program, Title : 日本経済新聞


  • 2021/08 -2022/03  令和3年度”オール近大”新型コロナウイルス感染症対策支援プロジェクト 研究提案代表者 
  • 2020/06 -2021/03  令和2年度”オール近大”新型コロナウイルス感染症支援プロジェクト 研究提案代表者 

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