萩原　央記 （ハギワラ　テルキ）

コミュニケーション情報 byコメンテータガイド

• コメント

  細胞に起こるエピジェネティックな変化（特にヒストンの化学修飾）について研究しています。その変化によって制御される遺伝子発現の仕組みをマウスや培養細胞を用いて調べています。

研究者情報

学位

• 博士（理学）（2005年03月 横浜市立大学）

ホームページURL

https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201401057891712103

J-Global ID

• 201401057891712103

研究キーワード

• チメロサール   メチル水銀   有機水銀   急性肺障害   Lung fluid clearance   炎症   肺   生理学   ナトリウムチャネル   

現在の研究分野（キーワード）

細胞に起こるエピジェネティックな変化（特にヒストンの化学修飾）について研究しています。その変化によって制御される遺伝子発現の仕組みをマウスや培養細胞を用いて調べています。

研究分野

• ライフサイエンス / 医療薬学
• ライフサイエンス / 生理学

経歴

• 2019年04月 - 現在  近畿大学理工学部講師
• 2008年 - 2019年03月  近畿大学理工学部助教

研究活動情報

論文

• Degradation-suppressed cocoonase for investigating the pro-peptide-mediated activation mechanism

  Nana Sakata; Ayumi Ogata; Mai Takegawa; Yuri Murakami; Misaki Nishimura; Mitsuhiro Miyazawa; Teruki Hagiwara; Shigeru Shimamoto; Yuji Hidaka

  Molecules 27 2 1 - 13 2022年11月 [査読有り]
  
• The propeptide sequence assists the correct folding required for the enzymatic activity of cocoonase

  Nana Sakata; Ayumi Ogata; Mai Takegawa; Nagisa Tajima; Misaki Nishimura; Teruki Hagiwara; Mitsuhiro Miyazawa; Shigeru Shimamoto; Yuji Hidaka

  Biochemical and Biophysical Research Communications 624 35 - 39 2022年10月 [査読有り]
  
• Maternal exposure to methylmercury causes an impairment in ependymal cilia motility in the third ventricle and dilation of lateral ventricles in mice offspring

  Teruki Hagiwara; Hajime Hagino; Kaho Ueda; Mina Nakama; Takeshi Minami

  Birth Defects Research 2020年07月 [査読有り]
  
• Colocalization of GPR120 and anterior pituitary hormone-producing cells in female Japanese Black cattle

  Sho NAKAMURA; Kohei NODA; Masafumi MIWA; Shiori MINABE; Teruki HAGIWARA; Akira HIRASAWA; Shuichi MATSUYAMA; Ryutaro MORIYAMA

  Journal of Reproduction and Development 66 2 135 - 141 2020年 [査読有り]
  
• AMP-activated protein kinase activation reduces the transcriptional activity of the murine luteinizing hormone β-subunit gene

  Ryutaro MORIYAMA; Koichi IWAMOTO; Teruki HAGIWARA; Saishu YOSHIDA; Takako KATO; Yukio KATO

  Journal of Reproduction and Development 66 2 97 - 104 2020年 [査読有り]
   

  Malnutrition is one of the factors that induces reproductive disorders. However, the underlying biological processes are unclear. AMP-activated protein kinase (AMPK) is an enzyme that plays crucial role as a cellular energy sensor. In the present study, we examined the effects of AMPK activation on the transcription of the murine gonadotropin subunit genes Cga, Lhb, and Fshb, and the gonadotropin-releasing hormone receptor Gnrh-r. Real-time PCR and transcription assay using LβT2 cells demonstrated that 5-amino-imidazole carboxamide riboside (AICAR), a cell-permeable AMP analog, repressed the expression of Lhb. Next, we examined deletion mutants of the upstream region of Lhb and found that the upstream regulatory region of Lhb (-2527 to -2198 b) was responsible for the repression by AICAR. Furthermore, putative transcription factors (SP1, STAT5a, and TEF) that might mediate transcriptional control of the Lhb repression induced by AICAR were identified. In addition, it was confirmed that both AICAR and a competitive inhibitor of glucose metabolism, 2-deoxy-D-glucose, induced AMPK phosphorylation in LβT2 cells. Therefore, the upstream region of Lhb is one of the target sites for glucoprivation inducing AMPK activation. In addition, AMPK plays a role in repressing Lhb expression through the distal -2527 to -2198 b region.
• 認定遺伝カウンセラー®の雇用に対する検査会社の視点

  仲間美奈; 白山大揮; 田村和朗; 川下理日人; 萩原央記; 巽純子; 南武志

  日本遺伝カウンセリング学会誌 40 3 85 - 93 2019年10月 [査読有り]
  
• 不飽和脂肪酸によるマウス精子の運動活性化メカニズムについて

  森山 隆太郎; 佐藤 弘章; 山本 悠人; 楳田 千明; 山本 悠愛; 若狭 郁美; 萩原 央記; 和田 哲幸

  The Journal of Reproduction and Development 65 Suppl. j107 - j107 (公社)日本繁殖生物学会 2019年09月
• Cloning and Functional Analysis of Digestive Enzyme Derived from Nephila Clavata

  Tsubasa Tagawa; Teruki Hagiwara; Shigeru Shimamoto; Yuji Hidaka

  Peptide Science 2018 101 - 101 2019年03月 [査読有り]
  
• Cilia movement of ependymal cells in the third ventricular surface is inhibited by the administration of methylmercury to mouse

  南 武志

  Journal of Clinical and Experimental Toxicology 1 1 1 - 6 2017年10月 [査読有り]
  
• Sodium influx through cerebral sodium-glucose transporter type 1 exacerbates the development of cerebral ischemic neuronal damage

  Yui Yamazaki; Shinichi Harada; Tetsuyuki Wada; Teruki Hagiwara; Shigeru Yoshida; Shogo Tokuyama

  EUROPEAN JOURNAL OF PHARMACOLOGY 799 103 - 110 2017年03月 [査読有り]
   

  We recently reported that cerebral sodium-glucose transporter type 1 (SGLT-1) plays a role in exacerbation of cerebral ischemia. However, the mechanism by which cerebral SGLT-1 acts remains unclear. Here we demonstrated that sodium influx through cerebral SGLT-1 exacerbates cerebral ischemic neuronal damage. SGLT-specific sodium ion influx was induced using alpha-methyl-D-glucopyranoside (alpha-MG). Intracellular sodium concentrations in primary cortical neurons were estimated using sodium-binding benzofuran isophthalate fluorescence. SGLT-1 knockdown in primary cortical neurons and mice was achieved using SGLT-1 siRNA. The survival rates of primary cultured cortical neurons were assessed using biochemical assays 1 day after treatment. Middle cerebral artery occlusion (MCAO) was used to generate a focal cerebral ischemic model in SGLT-1 knockdown mice. The change in fasting blood glucose levels, infarction development, and behavioral abnormalities were assessed 1 day after MCAO. Treatment with 200 mM alpha-MG induced a continuous increase in the intracellular sodium concentration, and this increase was normalized after a-MG removal. Neuronal SGLT-1 knockdown had no effect on 100 mu M H2O2-induced neuronal cell death; however, the knockdown prevented the neuronal cell death induced by 17.5 mM glucose and the co-treatment of 100 mu M H2O2/8.75 mM glucose. Neuronal SGLT-1 knockdown also suppressed the cell death induced by alpha-MG alone and the co-treatment of 100 mu M H2O2/0.01 mM alpha-MG. Our in vivo results showed that the exacerbation of cerebral ischemic neuronal damage induced by the intracerebroventricular administration of 5.0 mu g alpha-MG/mouse was ameliorated in cerebral SGLT-1 knockdown mice. Thus, sodium influx through cerebral SGLT-1 may exacerbate cerebral ischemia-induced neuronal damage.
• Gene expression of the concentration-sensitive sodium channel is suppressed in lipopolysaccharide-induced acute lung injury in mice

  Teruki Hagiwara; Shigeru Yoshida; Yuji Hidaka

  EXPERIMENTAL LUNG RESEARCH 43 3 150 - 157 2017年 [査読有り]
   

  Purpose: The concentration-sensitive sodium channel (Na-C) is expressed in alveolar type II epithelial cells and pulmonary microvascular endothelial cells in mouse lungs. We recently reported that Na-C contributes to amiloride-insensitive sodium transport in mouse lungs (Respiratory Physiology & Neurobiology, 2016). However, details regarding its physiological role in the lung remain unknown. To examine whether Na-C is involved in alveolar fluid clearance during an acute lung injury (ALI), we analyzed the relationship between Na-C gene expression in the lung and the development of pulmonary edema in lipopolysaccharide (LPS)-induced ALI mice. Methods: LPS-induced ALI mice were prepared by the intratracheal administration of LPS. Bronchoalveolar lavage (BAL) neutrophils and lung water content (LWCs) were used as a marker of ALI and pulmonary edema, respectively. Na-C protein production in the lung was detected by immunoblotting and immunofluorescence. The gene expressions of Na-C and the epithelial sodium channel (ENaC) of LPS-induced ALI mice were examined by quantitative RT-PCR over a time course of 14 days. Results: The BAL neutrophil count increased until day 2 after LPS administration and had nearly recovered by day 6. LWCs in LPS-induced mice gradually increased until day 8 and had recovered by day 14. The expression of the Na-C protein in the lungs of LPS-induced mice dramatically decreased from day 2 to day 6, but recovered by day 8. The mRNA expression of Na-C decreased in the lung, as well as those for alpha-, beta-, and gamma-ENaC during ALI. Thus, Na-C expression is suppressed during the development stage of pulmonary edema and then recovers in the convalescent phase. Conclusion: Our results suggest that suppression of the gene expression of Na-C is involved in the development of pulmonary edema in ALI.
• The organic mercury compounds, methylmercury and ethylmercury, inhibited ciliary movement of ventricular ependymal cells in the mouse brain around the concentrations reported for human poisoning

  Shigeru Yoshida; Shinsaku Matsumoto; Takuya Kanchika; Teruki Hagiwara; Takeshi Minami

  NEUROTOXICOLOGY 57 69 - 74 2016年12月 [査読有り]
   

  Functions of the nervous system are supported by the flow of cerebrospinal fluid (CSF), which is driven by the ciliary beating of ventricular ependymal cells. The aim of the present study was to examine whether methylmercury (MeHg), a substance with potent neurotoxicity in humans, affects the ciliary movement. The effects of another organic mercury compound, ethylmercury (EtHg), were also assessed for comparison. Toxicity of MeHg or EtHg was evaluated by measuring alterations in the ciliary beat frequency of ependymal cells lining the third ventricle of mouse brain slices. The obtained results were: (1) Both MeHg and EtHg started to inhibit ciliary motility between 1 and 3 mu M, the reported threshold limit of MeHg in humans. (2) An abrupt increase was observed in the inhibitory curves from 3 to 6 mu M for MeHg and EtHg. (3) The "give-in" concentration, i.e., concentration at which the cilia lose the ability to recover, for MeHg and EtHg was 6 mu M and 12 mu M, respectively. (4) Ciliary beating was irreversibly halted by MeHg and EtHg at concentrations above 12 mu M and 30 mu M, respectively. (5) The estimated half maximal inhibitory concentration (IC50) for MeHg and EtHg was 5.53 mu M and 5.80 mu M, respectively. Based on these findings, we conclude that: (a) Ependymal cell cilia movement in mice was inhibited by MeHg in a concentration-dependent manner around concentrations reported to cause poisoning in humans; EtHg inhibited ciliary motility to a less extent. (b) Inhibition of CSF flow by suppression of ciliary movement is suggested to be an additional route for MeHg poisoning in humans, especially in prenatal exposure than in adult exposure. (C) 2016 Elsevier B.V. All rights reserved.
• Contribution of concentration-sensitive sodium channels to the absorption of alveolar fluid in mice

  Teruki Hagiwara; Shigeru Yoshida

  RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY 231 45 - 54 2016年09月 [査読有り]
   

  The concentration-sensitive sodium channel (Na-c) is activated by an increase in the extracellular sodium concentration. Although the expression of Na-c in alveolar type II epithelial cells (AEC II) has been reported previously, the physiological role of Na-c in the lung has not been established. We characterized Na-c expression and examined amiloride-insensitive sodium transport mediated by Na-c in mouse lung. Immunofluorescence studies revealed that Na-c did not colocalize with either aquaporin 5 or cystic fibrosis transmembrane conductance regulator, but partially colocalized with the epithelial sodium channel)0 subunit. Immunoelectron microscopy studies showed that Na-c localized at the basolateral membrane of pulmonary microvascular endothelial cells (PMVECs). Na-c mRNA and protein were expressed in PMVECs isolated from the lungs of mice. Image analysis indicated that sodium influx into the alveolar wall was dependent on increases in extracellular sodium concentration. We conclude that Na, expressed in PMVECs and AEC II contributes to the reabsorption of sodium via an amiloride-insensitive pathway during alveolar fluid clearance. (C) 2016 Elsevier B.V. All rights reserved.
• Dynamic Expression of Peptidylarginine Deiminase 2 in Human Monocytic Leukaemia THP-1 Cells During Macrophage Differentiation

  Ikuko Hojo-Nakashima; Ryo Sato; Katsuhiko Nakashima; Teruki Hagiwara; Michiyuki Yamada

  JOURNAL OF BIOCHEMISTRY 146 4 471 - 479 2009年10月 [査読有り]
   

  Peptidylarginine deiminases (PADs) consist of five enzymes which are widely distributed in human and rodent tissues. The two types of enzymes are found in human peripheral blood cells; PAD4 mainly in granulocytes and monocytes and PAD2 in lymphocytes and macrophages. Little is known about the regulation of PAD expression in macrophages. Here, we report that PAD2 is expressed in human monocytic leukaemia THP-1 cells during differentiation into macrophages by 12-O-tetradecanoylphorbol-13-acetate. During this differentiation, the levels of PAD2 mRNA and protein increased concomitantly, indicating the transcriptional regulation of PAD2 gene expression in the cells. The treatment of THP-1-derived macrophages with calcium ionophore A23187 generated vimentin deimination and resulted in the disruption of vimentin filament organization. We discuss the possible role of vimentin deimination in cell physiology.
• Deimination of histone H2A and H4 at arginine 3 in HL-60 granulocytes

  T Hagiwara; Y Hidaka; M Yamada

  BIOCHEMISTRY 44 15 5827 - 5834 2005年04月 [査読有り]
   

  Interplay of various covalent modifications of histone tails has an essential role in regulation of chromatin function. Peptidylarginine deiminase (PADI) 4 deiminates protein arginine to citrulline in a Ca2+-dependent manner and is present in the nucleus of granulocyte-differentiated HL-60 cells. When these cells are treated with the calcium ionophore A23187, core histone deimination occurs. To determine the deimination sites of histones, histone species were purified by reverse-phase high-performance liquid chromatography (RP-HPLC) from the cells. Immunoblotting using antimodified citrulline antibody indicated that histones H2A, H3, and H4 but not H2B were deiminated. H2A and H4 were digested with Staphylococcus aureus V8 protease, and the digests were separated by RP-HPLC. Immuno dot-blotting and mass spectrometry showed that the deiminated residues were present in H2A (1-56) and H4 (1-52) regions but not in other regions. The H2A peptide (1-56) was digested with alpha-chymotrypsin, and the deiminated peptide was separated from the corresponding nondeiminated peptide by RP-HPLC. The deiminated residue was found to be limited to residues 1-23. Similarly, digestion of the H4 peptide (1-52) with endoproteinase Asp-N and separation of the deiminated peptide from the nondeiminated peptide indicated that the deiminated residue was limited to residues 1-23. Mass spectrometry of lysylendopeptidase digests of the H2A (1-23) and H4 (1-23) peptides showed that deimination occurred at arginine 3 of the N-terminal sequence Ac-SGRGK common to H2A and H4. These results suggest that PADI4 deiminates only a restricted site of target proteins in cells. Deimination of histones is discussed in relation to chromatin structure and function.
• Mechanism of the substrate recognition of peptidylarginine Deiminase V

  Yuji Hidaka; Teruki Hagiwara; Michiyuki Yamada

  Peptides 2004, Proceedings 637 - 638 2005年 [査読有り]
  
• Methylation of the Guanidino Group of Arginine Residues Prevents Citrullination by

  Teruki Hagiwara; Yuji Hidaka; Michiyuki Yamada

  FEBS Letters 579 4088 - 4092 2005年 [査読有り]
   

  ペプチジルアルギニンデイミナーゼの基質特異性とその反応阻害剤を合成し、報告した。
• Histone deimination antagonizes arginine methylation

  GL Cuthbert; S Daujat; AW Snowden; H Erdjument-Bromage; T Hagiwara; M Yamada; R Schneider; PD Gregory; P Tempst; AJ Bannister; T Kouzarides

  CELL 118 5 545 - 553 2004年09月 [査読有り]
   

  Methylation of arginine residues within histone H3 has been linked to active transcription. This modification appears on the estrogen-regulated pS2 promoter when the CARM1 methyltransferase is recruited during transcriptional activation. Here we describe a process, deimination, that converts histone arginine to citrulline and antagonizes arginine methylation. We show that peptidyl arginine deiminase 4 (PADI4) specifically deiminates, arginine residues R2, R8, R17, and R26 in the H3 tail. Deimination by PADI4 prevents arginine methylation by CARM1. Dimethylation of arginines prevents deimination by PADI4 although monomethylation still allows deimination to take place. In vivo targeting experiments on an endogenous promoter demonstrate that PADI4 can repress hormone receptor-mediated gene induction. Consistent with a repressive role for PADI4, this enzyme is recruited to the pS2 promoter following hormone induction when the gene is transcriptionally downregulated. The recruitment of PADI4 coincides with deimination of the histone H3 N-terminal tail. These results define deimination as a novel mechanism for antagonizing the transcriptional induction mediated by arginine methylation.
• Nuclear localization of peptidylarginine deiminase V and histone deimination in granulocytes

  K Nakashima; T Hagiwara; M Yamada

  JOURNAL OF BIOLOGICAL CHEMISTRY 277 51 49562 - 49568 2002年12月 [査読有り]
   

  Peptidylarginine deiminase (PAD) deiminates 2 arginine residues in proteins to citrulline residues Ca2+ dependently. There are four types of PADs, I, II, III, and V, in humans. We studied the subcellular distribution of PAD V in HL-60 granulocytes and peripheral blood granulocytes. Expression of green fluorescent protein-tagged PADs in HeLa cells revealed that PAD V is localized in the nucleus, whereas PAD I, II, and III are localized in the cytoplasm. PAD V deletion mutants indicated that the sequence residues 45-74 have a nuclear localization signal (NLS). A sequence feature of this NLS is a three-lysine residue cluster preceded by a proline residue and is not found in the three other PADs. Substitution of the lysine cluster by an alanine cluster abrogated the nuclear import activity. These results suggested that the NLS is a classical monopartite NLS. HL-60 granulocytes, neutrophils, and eosinophils stained with antibody specific for PAD V exhibited distinct positive signals in the nucleus. Subcellular fractionation of HL-60 granulocytes also showed the nuclear localization of the enzyme. When neutrophils were stimulated with calcium ionophore A23187, protein deimination occurred in the nucleus. The major deiminated proteins were identified as histones H2A, H3, and H4. The implication of PAD V in histone modifications is discussed.
• Deimination of arginine residues in nucleophosmin/B23 and histones in HL-60 granulocytes

  T Hagiwara; K Nakashima; H Hirano; T Senshu; M Yamada

  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 290 3 979 - 983 2002年01月 [査読有り]
   

  Peptidylarginine deiminases (PADS) convert arginine residues in proteins into citrulline residues Ca2+-dependently. PAD V was recently found in granulocyte-differentiated BL-60 cells. To find a target of PAD V, we incubated BL-60 granulocytes with the calcium ionophore A23187 and studied deiminated proteins by immunocytochemistry and immunoblotting using a monospecific antibody to modified citrulline residues. Immunocytochemical signals were found in the nucleus upon incubation with A23187. Immunoblotting indicated that 40-, 18-, 17-, and 14-kDa proteins were preferentially deiminated. The 40-kDa protein, which was focused to pI 5.0 on two-dimensional gel electrophoresis, was identified as nucleophosmin/B23 by mass spectrometry. The 18-, 17-, and 14-kDa proteins extracted with 0.4 N H2SO4 comigrated with histones H3, H2A, and H4, respectively, on two-dimensional gel electrophoresis specialized for histones. The citrulline content of histones amounted to about 10% of the histone molecules. We discuss the implications of deimination of these proteins for their nuclear functions. (C) 2002 Elsevier Science (USA).
• Molecular characterization of peptidylarginine deiminase in HL-60 cells induced by retinoic acid and 1 alpha,25-dihydroxyvitamin D-3

  K Nakashima; T Hagiwara; A Ishigami; S Nagata; H Asaga; M Kuramoto; T Senshu; M Yamada

  JOURNAL OF BIOLOGICAL CHEMISTRY 274 39 27786 - 27792 1999年09月 [査読有り]
   

  Three types of peptidylarginine deiminase (PAD), which converts a protein arginine residue to a citrulline residue, are widely distributed in animal tissues. Little is known about PAD of hemopoietic cells. We found that PAD activity in human myeloid leukemia HL-60 cells was induced with the granulocyte-inducing agents retinoic acid and dimethyl sulfoxide and with the monocyte-inducing agent 1 alpha,25-dihydroxyvitamin D-3. We cloned and characterized a PAD cDNA from retinoic acid-induced cells. The cDNA was 2,238 base pairs long and encoded a 663-amino acid polypeptide. The HL-60 PAD had 50-55% amino acid sequence identities with the three known enzymes and 73% identity with the recently cloned keratinocyte PAD. The recombinant enzyme differs in kinetic properties from the known enzymes. Immunoblotting and Northern blotting with an antiserum against the enzyme and the cDNA, respectively, showed that a protein of approximately 67 kDa increased concomitantly with increase of mRNA of approximately 2.6 kilobases during granulocyte differentiation. During monocyte differentiation the same mRNA and protein increased as in granulocyte differentiation. Neither the enzyme activity nor the protein was found in macrophage-induced cells. These results suggested that expression of the PAD gene is tightly linked to myeloid differentiation.
• ヒト骨髄性白血病細胞株HL-60の分化に伴い誘導されるペプチジルアルギニンデイミナーゼcDNAのクローニングと構造

  中島 克彦; 石神 昭人; 萩原 央記; 浅賀 宏昭; 倉元 雅史; 千秋 達雄; 山田 道之

  生化学 70 8 844 - 844 (公社)日本生化学会 1998年08月

講演・口頭発表等

• メチル水銀暴露によって引き起こされるマウス脳室上衣細胞の障害  [通常講演]

  萩原央記

  メチル水銀研究ミーティング 2019年12月 口頭発表（一般）
• エチル水銀およびチメロサールはマウス第三脳室上衣細胞の繊毛運動を抑制する  [通常講演]

  萩原 央記; 吉田 美咲; 南 武志

  メタルバイオサイエンス研究会2018 2018年11月 ポスター発表
• マウス第三脳室上衣細胞の繊毛運動性に対するメチル水銀の影響  [通常講演]

  上田佳穂; 萩野大; 萩原央記; 坂本峰至; 南武志

  メチル水銀研究ミーティング 2017年12月 口頭発表（一般）
• Effects of methylmercury and its chelators on mouse ependymal ciliary beat frequency  [招待講演]

  Takeshi Minami; Kaho Ueda; Dai Ogino; Teruki Hagiwara

  2nd International Caparica Conference on Pollutant Toxic Ions and Molecules 2017年11月 口頭発表（招待・特別）
• マウス第三脳室上衣細胞の繊毛運動に対するメチル水銀の影響  [通常講演]

  上田佳穂; 萩野大; 萩原央記; 南武志

  近畿大学大学院サイエンスネットワーク2017・第7回院生サミット 2017年09月 ポスター発表
• マウス第三脳室上衣細胞の繊毛運動性に対するメチル水銀の影響に関する研究  [招待講演]

  南 武志; 萩原央記; 吉田 繁

  メチル水銀研究ミーティング 2016年12月 口頭発表（招待・特別）
• Suppression of Concentration-Sensitive Sodium Channel during Lipopolysaccharide-Induced Acute Lung Injury in Mice  [通常講演]

  Teruki Hagiwara; Shigeru Yoshida

  IUBMB congress 2016年07月 ポスター発表
• マウス肺における濃度感受性ナトリウムチャネルの局在  [通常講演]

  萩原央記; 吉田繁

  日本生理学会大会 2016年03月 ポスター発表
• Bleomycin誘発肺炎モデルのマウス肺における濃度感受性ナトリウムチャネルの発現解析  [通常講演]

  萩原央記; 松尾航哉; 吉田繁

  日本生理学会 近畿生理学談話会 2015年10月 口頭発表（一般）
• In search of the evolutionary meaning of natriuretic peptides for cardiac function in terrestrial animals.  [通常講演]

  吉田 繁; 萩原 央記

  XXth International Congress of Zoology 2008年08月 Paris, France XXth International Congress of Zoology
  
• EXPRESSION REGULATION OF CONCENTRATION-SENSITIVE SODIUM CHANNEL IN MOUSE LUNG  [通常講演]

  萩原 央記; 吉田 繁

  33rd FEBS Congress and 11th IUBMB Conference 2008年07月 ギリシア アテネ 33rd FEBS Congress and 11th IUBMB Conference
   

  濃度感受性Na⁺チャネル（Na_C）は哺乳類の肺や後根神経節、末梢神経、脳室周囲器官等に発現している。Na_C発現は肺ではマウスの発生過程で大きく変化するが、生理学的な役割や発現調節の機構はよく分かっていない。この研究では、私たちはマウス肺におけるNa_Cの発現調節について調べた。Na_CmRNAとタンパク質は胎生15日目ではほとんど発現していない。Na_CmRNA発現は胎生17日目から大きく上昇し、成熟するまで高いレベルで維持される。一方、Na_Cタンパク質発現は胎生15目から出生5週目まではNa_CmRNAと同じ発現パターンを示すが、6週目からNa_CmRNAとは異なり減少する。6週目におけるNa_Cタンパク質の減少は、マウス肺の発達段階でNa_Cが転写後調節されていることを示唆する。マウスNa_Cの3’非翻訳領域は、数個のポリA付加部位とRNA結合タンパク質が結合するAU rich elementを含む2千塩基である。Na_C
• マウス肺における濃度感受性Na⁺チャネルの発現調節  [通常講演]

  萩原 央記; 西村 庸子; 月江 麻美; 峰岸 かつら; 吉田 繁

  日本分子学会、日本生化学会合同大会 2007年12月 横浜 日本分子学会、日本生化学会合同大会
   

  ＜目的＞濃度感受性Na⁺チャネル（Na_C; c: concentration）は遺伝子の相同性から電位感受性Na⁺チャネルファミリーに属する。Na_Cは細胞外Na⁺濃度上昇に応じて開くため、細胞外Na⁺センサーとして働き、体液調節に関与していると考えられる。マウスにおいて、脳の血液脳関門を欠く部位、肺のII型肺胞上皮細胞、後根神経節などにNa_Cの発現が報告されている。肺ではマウスの発達段階によってNa_Cの発現量が増減することが知られているが、その調節機構や意味はわかっていない。本研究の目的はマウス肺におけるNa_Cの発現調節機構の解明である。＜方法＞マウスの胎生後期から成熟期までの各段階で肺組織を採取した。Na_C mRNA量はRT-PCR、タンパク質量は坑Na_C抗体を用いたイムノブロッティングにより定量した。Na_C mRNAの3’非翻訳領域（3’UTR）を3’RACE法によって増幅し、poly A付加部位を同定した。＜結
• The concentration-sensitive Na+ channel (NaC) regulates growth of rat C6 glioma cells.  [通常講演]

  吉田 繁; 萩原 央記

  5th Forum of European Neuroscience 2006年07月 Vienna, Austria 5th Forum of European Neuroscience
  
• Regulation of gene expression by concentration-sensitive sodium channel in rat C6 glioma cells  [通常講演]

  萩原 央記; 武内 崇; 田中 北斗; 吉田 繁

  The 20th IUBMB Congress and 11th FAOBMB Congress 2006年06月 京都 The 20th IUBMB Congress and 11th FAOBMB Congress
   

  濃度感受性Na⁺チャネル（Na_C）は哺乳類で肺、心臓、末梢神経のシュワン細胞等に発現している。Na_Cノックアウトマウスの解析はNa_Cが細胞外Na⁺センサーであることを示唆したが、生物学的な機能はまだよく分かっていない。最近、egr-1遺伝子がNa_C発現細胞であるC6グリオーマ細胞において高濃度Na_Cl細胞外液で処理すると発現が抑制されることが報告された。この研究で私たちはRNAi法を用いてC6細胞で遺伝子発現調節におけるNa_Cの役割を調べた。定量的RT-PCRの結果は、C6細胞においてRNAiによるNa_Cの抑制がc-fosのmRNA量を抑制することを示した。Na_Cによってc-fosの発現が調節されるメカニズムを同定するために、私たちはERK経路を解析した。坑リン酸化ERK抗体を用いたイムノブロットは、RNAiによるNa_Cの抑制がERKのリン酸化に変化を引き起こすことを示した。これらの結果はERKを含むNa_C依存的なシグナル
• Concntration-sensitive Na⁺ channel (Na_C) is involved in the regulation of proliferation in rat C6 glioma cells  [通常講演]

  萩原 央記; 山口 博之; 武内 崇; 田中 北斗; 森本 与公; 吉田 繁

  日本生理学会 2006年03月 前橋 日本生理学会
   

  濃度感受性Na⁺チャネル（Na_C）はNa⁺センサーとして働き、細胞外Na⁺濃度が変化したとき開く。この研究はNa_Cを発現しているラットC6グリオーマ細胞を用いて、細胞増殖時の調節因子の一つとしてのNa_Cの機能を明らかにするために行なった。Na⁺指示薬（SBFI）とARGUS-50を用いたNa⁺の動態の画像解析は、細胞外Na⁺濃度を標準の140mMから190mMに上昇させたときの細胞内Na⁺濃度の上昇を明らかにした。Na⁺の流入がNa⁺ポンプの阻害剤（ouabain）またはNa⁺/K⁺/Cl^-共輸送体の阻害剤（bumetanide）によって抑制されたとき、この上昇は増大した。マンニトールを外液に加えても細胞内Na⁺濃度は変化しなかったため、浸透圧変化は関与していない。リアルタイムPCRによって測定されたEgr-1遺伝子の発現は、細胞外Na⁺濃度を上昇させたときや、Na⁺イオノフォアのmonensinによって

MISC

• マカク雄生殖系組織におけるACE2受容体およびTMPRSS2発現細胞の組織学的検討

  森山隆太郎; 中村祐哉; 萩原央記; 杉山真言; 三井一鬼; 中村翔; 鈴木樹理 日本内分泌学会雑誌 97 (3 (Web)) 2021年
• 不飽和脂肪酸によるマウス精子の運動活性化メカニズムについて

  森山 隆太郎; 佐藤 弘章; 山本 悠人; 楳田 千明; 山本 悠愛; 若狭 郁美; 萩原 央記; 和田 哲幸 The Journal of Reproduction and Development 65 (Suppl.) j107 -j107 2019年09月
• ジョロウグモ由来消化酵素のクローニングおよび機能解析

  田川翼; 萩原央記; 宮澤光博; 島本茂; 日高雄二 日本細胞生物学会大会(Web) 71st 2019年
• Effects of an antiepileptic drug phenytoin on oocyte Ca2+ oscillations and on sperm motility of the mouse

  Shigeru Yoshida; Takamichi Ishihata; Chiai Kitahara; Teruki Hagiwara JOURNAL OF PHYSIOLOGICAL SCIENCES 63 S231 -S231 2013年
• Development of the placenta may be supported by the expression of concentration-sensitive Na+ channels in mice

  Shigeru Yoshida; Ayano Mizutani; Akane Hiyama; Yuke Tadokoro; Shinichi Nishimura; Asami Komori; Sachiko Yamada; Teruki Hagiwara JOURNAL OF PHYSIOLOGICAL SCIENCES 60 S176 -S176 2010年
• Proliferation of rat C6 glioma cells is controlled by the concentration-sensitive Na+ channel (Na-C)

  Shigeru Yoshida; Hiroyuki Yamaguchi; Takashi Takeuchi; Hokuto Tanaka; Yoshiyuki Morimoto; Teruki Hagiwara NEUROSCIENCE RESEARCH 55 S141 -S141 2006年
• Search for the physiological function of the concentration-sensitive Na+ channel (Na-C)

  Shigeru Yoshida; Hokuto Tanaka; Takashi Takeuchi; Teruki Hagiwara ZOOLOGICAL SCIENCE 22 (12) 1436 -1436 2005年12月
• Substrate Recognition Mechanism of Peptidylarginine Deiminase IV

  HIDAKA Yuji; HAGIWARA Teruki; SATO Mamoru; YAMADA Michiyuki Peptide science : proceedings of the ... Japanese Peptide Symposium 2004 403 -404 2005年03月
• MECHANISM OF THE SUBSTRATE RECOGNITION OF PEPTIDYLARGININE DEIMINASE V

  Y. Hidaka; T. Hagiwara; M. Yamada JOURNAL OF PEPTIDE SCIENCE 10 208 -208 2004年

共同研究・競争的資金等の研究課題

• 肺水調節における濃度感受性ナトリウムチャネルの関与

  日本学術振興会：科学研究費助成事業

  研究期間 : 2008年 -2010年 

  代表者 : 萩原 央記

   

  肺胞上皮に発現している濃度感受性ナトリウムチャネル(Na_C)の生理的な機能は分かっていないため、マウス肺における水分調節にNa_Cが関与しているか検討した。リポ多糖投与により肺に炎症を誘発させると、Na_Cの発現量が著しく減少した。肺の水分含有量は炎症期に増大し、Na_C発現回復後に減少に転じた。これらの結果は炎症による肺胞上皮のNa_C発現の抑制が肺の水分含有量の増大を引き起こしていることを示唆する。

その他のリンク

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