Amplification of intracellular signaling initiated near the plasma membrane transporters

• Project/Area Number: 26460312
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Osaka Medical College (2016); National Cardiovascular Center Research Institute (2014-2015)
• Principal Investigator: Wakabayashi Shigeo 大阪医科大学, 医学部, 非常勤講師 (70158583)
• Co-Investigator(Renkei-kenkyūsha): Jin Meihua 国立循環器病研究センター, 肺高血圧症先端医学研究部, 研究員 (40746773)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 心筋リモデリング / 細胞内シグナル伝達 / Ca2+結合蛋白質 / 心肥大 / 低酸素刺激 / ノックアウトマウス / イオン輸送体 / シグナル伝達 / 遺伝子改変マウス / 心不全 / カテコールアミン / Na+/H+交換輸送体 / ベータリセプター

Outline of Final Research Achievements

Many problems have emerged at the beginning of study, and we changed the direction of study related to NHE1. We proceeded the study successfully for the most part. (1) A beta-blocker were found to have a potential for improvement of the disease in a Tg mouse of NHE1 which causes a heart failure. (2) In vitro study using cultured cells revealed that NHE1-binding protein CHP3 negatively regulates cardiomyocyte hypertrophy via inhibition of GSK3beta. (3) Analysis of CHP3 knockout mice revealed that CHP3 negatively regulates cardiac hypertrophy caused by a chronic hypoxia by regulating the expression level of CHP3.

Research Products

• [Journal Article] Tescalcin is a potential target of class I histone deacetylase inhibitors in neurons. (2017)
  • Author(s): Takamatsu G, Katagiri C, Tomoyuki T, Shimizu-Okabe C, Nakamura W, Nakamura-Higa M, Hayakawa T, Wakabayashi S, Kondo T, Takayama C, Matsushita M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 482 Issue: 4 Pages: 1327-1333
  • DOI: 10.1016/j.bbrc.2016.12.036
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Possible Signaling Pathways Mediating Neuronal Calcium Sensor-1-Dependent Spatial Learning and Memory in Mice (2017)
  • Author(s): Tomoe Y Nakamura, Shu Nakao, Yukako Nakajo, Jun C Takahashi, Shigeo Wakabayashi, Hiroji Yanamoto
  • Journal Title: PloS one Volume: 12 Issue: 1 Pages: 1-1
  • DOI: 10.1371/journal.pone.0170829
  • Peer Reviewed / Open Access
• [Journal Article] Neuronal Ca 2+ sensor-1 contributes to stress tolerance in cardiomyocytes via activation of mitochondrial detoxification pathways (2016)
  • Author(s): Tomoe Y Nakamura, Shu Nakao, Shigeo Wakabayashi
  • Journal Title: Journal of molecular and cellular cardiology Volume: 99 Pages: 23-34
  • DOI: 10.1016/j.yjmcc.2016.08.013
  • Peer Reviewed / Open Access
• [Journal Article] Activation of TRPV2 negatively regulates the differentiation of mouse brown adipocytes. (2016)
  • Author(s): Sun W, Uchida K, Takahashi N, Iwata Y, Wakabayashi S, Goto T, Kawada T, Tominaga M.
  • Journal Title: Pfluger Archiv. Eur. J. Physiol. Volume: 468 (9) Issue: 9 Pages: 1527-1540
  • DOI: 10.1007/s00424-016-1846-1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Lack of TRPV2 impaired thermogenesis in mouse brown adipose tissue. (2016)
  • Author(s): 1.Sun, W., Uchida, K., Suzuki, Y., Zhou, Y., Kim, M., Takayama, Y., Takahashi, N., Goto, T., Wakabayashi, S., Kawada, T., Iwata, Y., and Tominaga, M
  • Journal Title: EMBO Report Volume: 17 Issue: 3 Pages: 383-399
  • DOI: 10.15252/embr.201540819
  • Peer Reviewed / Open Access
• [Journal Article] Cancer cachexia causes skeletal muscle damage via transient receptor potential vanilloid 2-independent mechanisms, unlike muscular dystrophy (2015)
  • Author(s): Yuko Iwata, Nobuyuki Suzuki, Hitomi Ohtake, Shinya Kamauchi, Naohiro Hashimoto, Tohru Kiyono, Shigeo Wakabayashi
  • Journal Title: Journal of Cachexia, Sarcopenia and Muscle Volume: 印刷中 Issue: 3 Pages: 1-11
  • DOI: 10.1002/jcsm.12067
  • Peer Reviewed / Open Access
• [Journal Article] Calcineurin B homologous protein 3 negatively regulates cardiomyocyte hypertrophy via inhibition of glycogen synthase kinase 3 phosphorylation (2015)
  • Author(s): 4.Kobayashi S., Nakamura, T.Y., and Wakabayashi S.
  • Journal Title: J. Mol. Cell. Cardiol Volume: 84 Pages: 133-142
  • Peer Reviewed
• [Journal Article] Osmosensation in TRPV2 dominant negative expressing skeletal muscle fibres. (2015)
  • Author(s): 3.Zanou, N., Mondin, L., Fuster, C., Seghers, F., Dufour, I., Clippele, M., Schakman, O., Tajeddine, N., Iwata, Y., Wakabayashi, S., Voets, T., Allard, B., and Gailly, P
  • Journal Title: J. Physiol. Volume: 593(17) Issue: 17 Pages: 3849-3863
  • DOI: 10.1113/jp270522
  • Peer Reviewed
• [Journal Article] Stimulus-dependent regulation of nuclear Ca2+ signaling in cardiomyocytes: a role of neuronal calcium sensor-1 (2015)
  • Author(s): 2.Shu Nakao, Shigeo Wakabayashi, Tomoe Y. Nakamura. Stimulus-dependent regulation of nuclear Ca2+ signaling in cardiomyocytes: a role of neuronal calc
  • Journal Title: PLoS ONE Volume: 10 Issue: 4 Pages: e0125050-e0125050
  • DOI: 10.1371/journal.pone.0125050
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Calcineurin B homologous protein 3 negatively regulates cardiomyocyte hypertrophy via inhibition of glycogen synthase kinase 3 phosphorylation (2015)
  • Author(s): Soushi Kobayashi, Tomoe Y. Nakamura, Shigeo Wakabayashi
  • Journal Title: Journal of Molecular Cellular Cardiology Volume: 未定
  • Peer Reviewed
• [Journal Article] Deficiency of a lipid droplet protein, Perilipin 5, suppresses myocardial lipid accumulation, thereby preventing diabetes-induced heart malfunction (2014)
  • Author(s): Kenta Kuramoto, Fumie Sakai, Nana Yoshinori, Tomoe Y. Nakamura, Shigeo Wakabayashi, Tomoko Kojidani, Tokuko Haraguchi, Fumiko Hirose,Takashi Osumi
  • Journal Title: Molecular and Cellular Biology Volume: 34(14) Issue: 14 Pages: 2721-2731
  • DOI: 10.1128/mcb.00133-14
  • Peer Reviewed / Open Access
• [Journal Article] Na^+/H^+ exchanger 1 is regulated via its lipid-interacting domain, which functions as a molecular switch : A pharmacological approach using indolocarbazole compounds (2014)
  • Author(s): Shimada-Shimizu N, Hisamitsu T, Nakamura TY, Hirayama N, Wakabayashi S
  • Journal Title: Mol. Pharmacol Volume: 85(1) Issue: 1 Pages: 18-28
  • DOI: 10.1124/mol.113.089268
  • Peer Reviewed / Open Access
• [Presentation] カルシニュリンB様蛋白質3（CHP3）ノックアウトマウスを用いた慢性低酸素負荷による心肥大 (2017)
  • Author(s): 金 美花、若林 繁夫、古林創史、土持 裕胤、白井 幹康、ピアソン ジェームズ、
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: 浜松アクトシティコングレスセンター
  • Year and Date: 2017-03-28
• [Presentation] マウス大動脈狭窄心不全モデルにおける果実に含有するポリフェノール類の病態改善効果の検討 (2016)
  • Author(s): 若林繁夫、スクマラン・ビジェヤクマ、金美花、稲垣薫克、土持裕胤、白井幹康
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-09-25
• [Presentation] カルシニュリンB様蛋白質3（CHP3）ノックアウトマウスの作成と心機能解析 (2016)
  • Author(s): 金美花、若林繁夫、古林創史、土持裕胤、白井幹康
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌
  • Year and Date: 2016-03-22
• [Presentation] 細胞内Ca2+センサーによる新規代謝調節経路 (2015)
  • Author(s): 西谷（中村）友重、中尾周、中川修、若林繁夫
  • Organizer: BMB2015 第38回 日本分子生物学会年会 第88回日本生化学会 合同大会
  • Place of Presentation: 神戸国際会議場・展示場
  • Year and Date: 2015-12-01
• [Presentation] Na+/H+交換輸送体NHE1とカルシニューリンとの結合に対するGタンパク質共役型受容体刺激の効果 (2015)
  • Author(s): 久光 隆、若林繁夫、中川 修
  • Organizer: BMB2015 第38回 日本分子生物学会年会 第88回日本生化学会 合同大会
  • Place of Presentation: 神戸国際会議場・展示場
  • Year and Date: 2015-12-01
• [Presentation] 継続的な有酸素運動はCa2+センサー蛋白質欠損で起こるマウスの肥満を解消できる (2015)
  • Author(s): 若林繁夫、中尾周、稲垣薫克、土持裕胤、中村―西谷友重、白井幹康
  • Organizer: BMB2015 第38回日本分子生物学会年会および第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸国際会議場・展示場
  • Year and Date: 2015-12-01
• [Presentation] 細胞内カルシウムセンサーによる心筋ストレス防御機構 (2015)
  • Author(s): 西谷（中村）友重、中尾周、若林繁夫
  • Organizer: 心血管膜輸送研究会2015
  • Place of Presentation: 岡崎、生理学研究所
  • Year and Date: 2015-10-29
• [Presentation] 胞内Ca2+センサー蛋白質を介した心筋内ストレス防御機構 (2015)
  • Author(s): 西谷（中村）友重、中尾周、若林繁夫
  • Organizer: 第108回 近畿生理談話会
  • Place of Presentation: 近畿大学
  • Year and Date: 2015-10-24
• [Presentation] 癌悪液質における筋傷害にCa2+透過チャネルは関与するか？ (2015)
  • Author(s): 岩田裕子、 鈴木伸之、若林繁夫
  • Organizer: 第1回日本筋学会学術集会
  • Place of Presentation: 国立精神・神経医療研究センター
  • Year and Date: 2015-07-08
• [Presentation] Absence of TRPV2 impaired BAT thermogenesis in mice. (2015)
  • Author(s): Sun, W., Uchida, K., Suzuki, Y., Zhou, Y., Kim, M., Takayama, Y., Takahashi, N., Goto, T., Wakabayashi, S., Kawada, T., Y., and Tominaga, M
  • Organizer: The 5th International Ion Channel Conference
  • Place of Presentation: Luzhou, Sichuan, China
  • Year and Date: 2015-06-26
  • Int'l Joint Research
• [Presentation] Aerobic treadmill training prevents the obesity caused by gene disruption of Ca2+-sensor protein in mice (2015)
  • Author(s): Wakabayashi, S., Nakao, S., Inagaki, T., Tsuchimochi, H., Nakamura, T.Y., Shirai, M.
  • Organizer: 第92回日本生理学会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2015-03-23
• [Presentation] Regulation of energy metabolism by intracellular Ca2+ signals (2015)
  • Author(s): Nakamura-Nishitani, T.Y., Nakao, S., Nakagawa, O., Wakabayashi, S
  • Organizer: 第92回日本生理学会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2015-03-23
• [Presentation] Effects of Epac-specific inhibitor, ESI-09 on heart failure model mice (2015)
  • Author(s): Jin , M., Wakabayashi, S., Tsuchimochi, H., Shirai, M.
  • Organizer: 第92回日本生理学会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2015-03-22
• [Presentation] Role of Ca2+ sensor-1 in learning and memory in mice (2015)
  • Author(s): Nakao, S., Nakajo, Y., Takahashi, J.C., Nakagawa, O., Wakabayashi, S., Yamamoto, H., and Nakamura-Nishitani, T.Y.
  • Organizer: 第92回日本生理学会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2015-03-21
• [Presentation] Calcineurin B homologous protein (CHP3) regulates phosphorylation of GSK3beta (2015)
  • Author(s): Kobayashi, S., Wakabayashi, S
  • Organizer: 第92回日本生理学会
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2015-03-21
• [Presentation] Cardioprotective Role of Neuronal Ca2+-Sensor -1 during Stress (2015)
  • Author(s): Nakamura, T.Y., Nakao, S., Wakabayashi, S
  • Organizer: Biophysical Society 59th Annual Meeting
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2015-02-11
• [Presentation] Calcineurin B homologous protein 3 (CHP3)はAkt-GSK3シグナルを調節する (2014)
  • Author(s): 古林創史、若林繁夫
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-18
• [Presentation] マウス心筋細胞における核内カルシウム動態の生理的役割：細胞内カルシウム動態との関連について (2014)
  • Author(s): 中尾 周、若林繁夫、中村(西谷)友重
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-17
• [Presentation] マウスの空間学習・記憶におけるカルシウムセンサーNCS-1の役割 (2014)
  • Author(s): 中村(西谷)友重、中尾 周、中城友香子、高橋 淳、若林繁夫、柳本広二
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-16
• [Presentation] Na+/H+交換輸送体のスフィンゴ脂質による活性化 (2014)
  • Author(s): 若林繁夫、久光 隆、西谷(中村)友重、白井幹康
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-10-16
• [Presentation] ストレス下の心筋におけるサバイバル機構：Ca2+センサーNCS-1の役割 (2014)
  • Author(s): 中村(西谷)友重、中尾 周、若林繁夫
  • Organizer: 第5回Molecular Cardiovascular Conference II
  • Place of Presentation: 神戸ベイシェラトンホテル＆タワーズ
  • Year and Date: 2014-09-05