Oncogene TRE regulates voltage-gated Na^+ channel remodeling

• Project/Area Number: 21590934
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Oita University
• Principal Investigator: ONO Katsushige 大分大学, 医学部, 教授 (40253778)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Naチャネル / 不整脈 / リモデリング / Ca過負荷 / 心筋 / 細胞内カルシウム過負荷 / ユビキチン / 脱ユビキチン / Na^+チャネル / 心房細動 / イオンチャネル / プロテアソーム

Research Abstract

In cardiomyocytes, as a long term influence of the arrhythmias, ion channels such as voltage-dependent Na^+ channel may suffer from remodeling. As a consequence of cellular calcium overload, calmodulin is highly activated to suppress TRE17 functions to deubiquitinate the channel. Although Na^+ channel synthesis was intact, channel degradation ration exceeds the protein life span, which leads the down-regulation of Na+channels in the heart as a long-term impact on the cardiac excitability.

Research Products

• [Journal Article] Sodium channel as a target for molecular arrhythmia (2011)
  • Author(s): K. Ono
  • Journal Title: J Arrhythmia Volume: 27 Pages: 91-95
• [Journal Article] Sodium channel as a gate for molecular arrhythmology (2011)
  • Author(s): K.Ono
  • Journal Title: J Arrhythmia Volume: 27 Pages: 91-95
  • Peer Reviewed
• [Journal Article] Point mutations in domain II of the voltage-gated sodium channel gene in deltamethrin-resistant Aedes aegypti(Diptera : Culicidae) (2010)
  • Author(s): R. Srisawat, N. Komalamisra, Y. Eshita, M. Zheng, K. Ono, T. Q. Itoh, A. Matsumoto, S. Petmitr, Y. Rongsriyam
  • Journal Title: Appl Entomol Zool Volume: 45 Pages: 275-282
  • NAID: 130000248672
• [Journal Article] β-Adrenergic-AMPK Pathway Phosphorylates Acetyl-CoA Carboxylase in a High-epinephrine Rat Model (2010)
  • Author(s): A. Hattori, K. Mawatari, S. Tsuzuki, E. Yoshioka, S. Toda, M. Yoshida, S. Yasui, H. Furukawa, M. Morishima, K. Ono, T. Ohnishi, M. Nakano, N. Harada, A. Takahashi, Y. Nakaya
  • Journal Title: SPORTS. Obesity Volume: 18 Pages: 45-54
• [Journal Article] Nonapeptide hormones oxytocin and vasopression distinctly regulate Ca_V1. 2 L-type Ca^<2+> channel expression in cardiomyocytes (2010)
  • Author(s): M. Morishima, S. Tahara, Y. Wang, T. Kaku, K. Ono
  • Journal Title: J Arrhythmia Volume: 26 Pages: 111-118
• [Journal Article] Intracellular Ca^<2+>-and PKC-dependent upregulation of T-type Ca^<2+> channels in LPC-stimulated cardiomyocytes (2010)
  • Author(s): M. Zheng, Y. Wang, L. Kang, T. Shimaoka, F. Marni, K. Ono
  • Journal Title: J Mol Cell Cardiol Volume: 48 Pages: 131-139
• [Journal Article] Intracellular Ca2+- and PKC-dependent upregulation of T-type Ca2+ channels in LPC-stimulated cardiomyocytes (2010)
  • Author(s): M.Zheng, Y.Wang, L.Kang, T.Shimaoka, F.Marni, K.Ono
  • Journal Title: J Mol Cell Cardiol Volume: 48 Pages: 131-139
  • Peer Reviewed
• [Journal Article] Nonapeptide hormones oxytocin and vasopression distinctly regulate CaV1.2 L-type Ca2+ channel expression in cardiomyocytes (2010)
  • Author(s): M.Morishima, S.Tahara, Y.Wang, T.Kaku, K.Ono
  • Journal Title: J Arrhythmia Volume: 26 Pages: 111-118
  • Peer Reviewed
• [Journal Article] β-Adrenergic-AMPK Pathway Phosphorylates Acetyl-CoA Carboxylase in a High-epinephrine Rat Model, SPORTS (2010)
  • Author(s): A.Hattori, K.Mawatari, S.Tsuzuki, E.Yoshioka, S.Toda, M.Yoshida, S.Yasui, H.Furukawa, M.Morishima, K.Ono, T.Ohnishi, M.Nakano, N.Harada, A.Takahashi, Y.Nakaya
  • Journal Title: Obesity Pages: 45-54
  • Peer Reviewed
• [Journal Article] Point mutations in domain II of the voltage-gated sodium channel gene in deltamethrin-resistant Aedes aegypti (Diptera : Culicidae) (2010)
  • Author(s): R.Srisawat, N.Komalamisra, Y.Eshita, M.Zheng, K.Ono, T.Q.Itoh, A.Matsumoto, S.Petmitr, Y.Rongsriyam
  • Journal Title: Appl Entomol Zool Volume: 45 Pages: 275-282
  • NAID: 130000248672
  • Peer Reviewed
• [Journal Article] Telmisartan, an angiotensin II type 1 receptor antagonist, attenuates T-type Ca^<2+> channel expression in neonatal rat cardiomyocytes (2009)
  • Author(s): M. Morishima, Y Wang, Y. Akiyoshi, S. Miyamoto, K. Ono
  • Journal Title: Eur J Pharmacol Volume: 609 Pages: 105-112
• [Journal Article] 17β-estradiol modulates expression of low-voltage-activated Ca_V3. 2 T-type Ca^<2+> channel via ERKs pathway in cardiomyocytes (2009)
  • Author(s): F. Marni, Y. Wang, M. Morishima, T. Shimaoka, T. Uchino, M. Zheng, T. Kaku, K. Ono
  • Journal Title: Endocrinology Volume: 150 Pages: 879-888
• [Presentation] p38 MAPキナーゼ活性によって調節を受ける転写因子Csx/Nkx2.5及びGATA4に依存する心筋イオンチャネルの初期分化 (2011)
  • Author(s): 鄭明奇
  • Organizer: 第62回西日本生理学会
  • Place of Presentation: 佐賀
  • Year and Date: 2011-10-15
• [Presentation] Hypoxia-induced factor (Hif-1)を介した心筋T型カルシウムチャネルの発現制御機構 (2011)
  • Author(s): 窪田浩志
  • Organizer: 第21回日本病態生理学会
  • Place of Presentation: 東京
  • Year and Date: 2011-08-20
• [Presentation] 心房細動の発症基盤と治療薬の作用機序 (2011)
  • Author(s): 小野克重
  • Organizer: 静岡ハートフォーラム
  • Place of Presentation: 静岡
  • Year and Date: 2011-06-16
• [Presentation] 心房細動の発症とイオンチャネルリモデリング (2011)
  • Author(s): 小野克重
  • Organizer: 秋田ハートクラブ発表会
  • Place of Presentation: 秋田
  • Year and Date: 2011-06-08
• [Presentation] Transcription factor Csx/Nkx2.5 and nFAT regulate expression of Cav3.2 T-type Ca2+ channel via protein kinase C actions (2010)
  • Author(s): Ono K
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
  • Year and Date: 2010-03-17
• [Presentation] エタノールは肺静脈細胞のT型Ca2+チャネルの発現を増加させる (2010)
  • Author(s): 王岩, 森島真幸, 賀来俊彦, 小野克重
  • Organizer: 第20回日本病態生理学会大会
  • Place of Presentation: 奈良
• [Presentation] Protein kinase C as an upstream signal to activate Csx/Nkx2. 5 and nFAT transcription to accelerate Cav3. 2 Ca2+channel expression (2010)
  • Author(s): 王岩, 森島真幸、嶋岡徹, 小野克重
  • Organizer: 第74回日本循環器学会学術集会
  • Place of Presentation: 京都
• [Presentation] Transcription factor Csx/Nkx2. 5 and nFAT regulate expression of Cav3. 2 T-type Ca2+channel via protein kinase C actions (2010)
  • Author(s): Ono K, Morishima M, Wang Y
  • Organizer: 第83回日本薬理学会年会
  • Place of Presentation: 大阪
• [Presentation] Effects of physical exercise on cardiac Ca2+channel expression in SPORTS rat, a novel rat-strain feautured by high levels of voluntary wheel-running activity (2010)
  • Author(s): Morishima M, Wang Y, Akiyoshi Y, Ono K
  • Organizer: 第20回ISHR世界大会2010京都
  • Place of Presentation: 京都
• [Presentation] アンジオテンシン受容体を介した心筋T型カルシウムチャネルの発現抑制 (2010)
  • Author(s): 森島真幸, 王岩, 秋吉裕子, 小野克重
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
• [Presentation] Nonapeptide hormone oxytocin regulates Cav1.2 L-type calcium channel expression in cardiomyocytes (2009)
  • Author(s): Morishima M
  • Organizer: 第26回ISHR日本部会総会
  • Place of Presentation: 札幌
  • Year and Date: 2009-12-04
• [Presentation] Protein kinase C as a key modulator to switch isoforms from Cav3.2 to Cav3.1 of the T-type Ca2+ channel in neonatal rat crdiomyocytes (2009)
  • Author(s): Wnag Y
  • Organizer: APHRS 2009
  • Place of Presentation: 北京
  • Year and Date: 2009-10-22
• [Presentation] PKCは新生ラッと心筋細胞のT型Ca2+チャネルのSubtype変換を制御する (2009)
  • Author(s): 王岩, 森島真幸, 賀来俊彦, 嶋岡徹, 康林, 小野克重
  • Organizer: 第19回日本病態生理学会大会
  • Place of Presentation: 所沢
• [Presentation] Oxytocinによる心筋L型Ca2+チャネルの転写制御機 (2009)
  • Author(s): 森島真幸, 田原慎太郎, 王岩, 秋吉裕子, 賀来俊彦, 小野克重
  • Organizer: 第19回日本病態生理学会大会
  • Place of Presentation: 所沢
• [Presentation] シンポジウム (2009)
  • Author(s): 小野克重
  • Organizer: 第26回日本心電学会学術集会
  • Place of Presentation: 京都
• [Presentation] Oxytocinは幼若ラット心筋細胞において転写因子CREBを介してL型Ca2+チャネル(CaV1. 2)発現を抑制する (2009)
  • Author(s): 森島真幸, 田原慎太郎, 秋吉裕子、王岩, 賀来俊彦, 小野克重
  • Organizer: 第26回日本心電学会学術集会
  • Place of Presentation: 京都
• [Presentation] エタノールは肺静脈心筋細胞のT型Ca2+チャネルの発現を増加させる (2009)
  • Author(s): 王岩, 森島真幸, 康林, 賀来俊彦, 小野克重
  • Organizer: 第26回日本心電学会学術集会
  • Place of Presentation: 京都
• [Presentation] PKC活性に依存する新生ラット心筋細胞T型Ca2+チャネルのSubtype変換 (2009)
  • Author(s): 王岩, 森島真幸, 賀来俊彦, 小野克重
  • Organizer: 第60回西日本生理学会
  • Place of Presentation: 福岡
• [Presentation] Nonapeptide hormone oxytocin regulates Cav1. 2 L-type calcium channel expression in cardiomyocytes (2009)
  • Author(s): Morishima M, Wang Y, Kaku T, Ono K
  • Organizer: 第26回ISHR日本部会総会
  • Place of Presentation: 札幌
• [Presentation] Protein kinase C as a key modulator to switch isoforms from Cav3. 2 to Cav3. 1 of the T-type Ca2+channel in neonatal rat crdiomyocytes
  • Author(s): Wang Y, Morishima M, Kang L, Kaku T, Ono K
  • Organizer: APHRS 2009(2nd Asia Pacific Heart Rhythm Society Scientific Sessions 5th Asia Pacific Atrial Fibrillation Symposium)
  • Place of Presentation: Beijing International Convention Center, China
• [Book] 不整脈2011 (2011)
  • Author(s): 小野克重
  • Total Pages: 10
  • Publisher: メディカルレビュー社
• [Book] Caハンドリング異常と不整脈、ここまで進んだ不整脈研究の最新動向(別冊・医学のあゆみ) (2011)
  • Author(s): 小野克重
  • Total Pages: 7
  • Publisher: 医歯薬出版社
• [Book] アミオダロンの薬理学的特徴と心房細動治療への期待 (2011)
  • Author(s): 小野克重
  • Total Pages: 3
  • Publisher: ライフサイエンス社
• [Book] Heart;心臓血管系 (2011)
  • Author(s): 小野克重
  • Total Pages: 13
  • Publisher: 医学出版社