Isoprenaline-induced cardiac fibrosis in Tric-a-knockout mice

• Project/Area Number: 24659131
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Kyoto University
• Principal Investigator: YAMAZAKI Daiju 京都大学, 生理化学ユニット, 講師 (40467428)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: TRICチャネル / 心臓線維化 / イソプロテレノール / 心筋細胞死 / ネクローシス / TRIC-A

Research Abstract

TRIC-A is abundantly expressed in excitable tissues. Cardiac fibrosis was significantly induced by chronic beta-adrenergic receptor stimulation (Isoproterenol, Iso) in Tric-a-knockout mice. In this study, to investigate the underlying mechanisms, we focused on cardiomyocyte death. Elevated serum troponin T level and increased membrane permeability of evans blue dye which means cardiomyocyte necrosis induced by isoproterenol stimulation were detected in Tric-a-knockout mice. Moreover mitochondrial dysfunction was observed in Iso-stimulated Tric-a-knockout heart under electron microscopic examination.
Thus, it is suggested that remarkable cardiomyocyte necrosis is at least in part related to Iso-induced cardiac fibrosis in Tric-a-knockout mice.

Research Products

• [Journal Article] Trimeric intracellular cation channels and sarcoplasmic/endoplasmic reticulum calcium homeostasis (2014)
  • Author(s): Zhou X, Lin P, Yamazaki D, Park KH, Komazaki S, Chen SR, Takeshima H, Ma J
  • Journal Title: Circ Res Volume: 114 Issue: 4 Pages: 706-716
  • DOI: 10.1161/circresaha.114.301816
  • Peer Reviewed
• [Journal Article] TRIC-B channels display labile gating: evidence from the TRIC-A knockout mouse model. (2013)
  • Author(s): Venturi, E., Matyjaszkiewicz, A., Pitt, S. J., Tsaneva-Atanasova, K., Nishi, M., Yamazaki, D., Takeshima, H. & Sitsapesan, R.
  • Journal Title: Pflugers Arch. Volume: 465 Issue: 8 Pages: 1135-1148
  • DOI: 10.1007/s00424-013-1251-y
  • Peer Reviewed
• [Journal Article] TRIC channels supporting efficient Ca^<2+> release from intracellular stores (2013)
  • Author(s): Venturi E, Sitsapesan R, Yamazaki D, Takeshima H
  • Journal Title: Pflugers Arch. Volume: 465 Issue: 2 Pages: 187-195
  • DOI: 10.1007/s00424-012-1197-5
  • Peer Reviewed
• [Journal Article] The Roles of Calcium and Phosphorus in Cardiovascular Diseases. TRIC channel and hypertension (2013)
  • Author(s): 山崎大樹、陶晟辰、竹島浩
  • Journal Title: Clin Calcium. Volume: 23(CliCa1304543550) Pages: 543-550
• [Journal Article] Facilitated hyperpolarization signaling in vascular smooth muscle overexpressing TRIC-A channels. (2013)
  • Author(s): Tao, S., Yamazaki, D., Komazaki, S., Zhao, C., Iida, T., Kakizawa, S., Imaizumi, Y. & Takeshima, H.
  • Journal Title: J. Biol. Chem. Volume: 288 Issue: 22 Pages: 15581-15589
  • DOI: 10.1074/jbc.m112.435396
  • Peer Reviewed
• [Journal Article] TRIC channel and hypertension (2013)
  • Author(s): Yamazaki D, Tao S, Takeshima H.
  • Journal Title: Clin Calcium Volume: 23 Pages: 543-550
• [Journal Article] TRIC-B channels display labile gating: evidence from the TRIC-A knockout mouse model. (2013)
  • Author(s): Venturi E, Matyjaszkiewicz A, Pitt SJ, Tsaneva-Atanasova K, Nishi M, Yamazaki D, Takeshima H, Sitsapesan R
  • Journal Title: Pflugers Archives Volume: -
  • Peer Reviewed
• [Journal Article] The Roles of Calcium and Phosphorus in Cardiovascular Diseases. TRIC channel and hypertension. (2013)
  • Author(s): Yamazaki D, Tao S, Takeshima H.
  • Journal Title: Clinical Calcium Volume: 23 Pages: 543-550
  • Peer Reviewed
• [Journal Article] Facilitated hyperpolarization signaling in vascular smooth muscle overexpressing TRIC-A channels. (2013)
  • Author(s): Tao S, Yamazaki D, Komazaki S, Zhao C, Iida T, Kakizawa S, Imaizumi Y, Takeshima H.
  • Journal Title: Journal of Biological Chemistry Volume: -
  • Peer Reviewed
• [Journal Article] TRIC (trimeric intracellular cation)-Aチャネルは血管平滑筋において血圧調節に寄与する (2012)
  • Author(s): 山崎大樹
  • Journal Title: YAKUGAKU ZASSHI Volume: 132 Pages: 1037-1043
  • NAID: 130001888722
• [Journal Article] TRIC(trimeric intracellular cation)-A channels contribute to blood pressure maintenance in vascular smooth muscle (2012)
  • Author(s): Yamazaki D
  • Journal Title: Yakugaku Zasshi Volume: 132 Pages: 1037-1043
  • NAID: 130001888722
  • Peer Reviewed
• [Presentation] The MBOAT family protein Mitsugumin56 contributes to postnatal maturation in the muscle sarcoplasmic reticulum (2014)
  • Author(s): Van B, Nishi M, Komazaki S, Park KH, Yamazaki D, Ma J, Takeshima H
  • Organizer: Biophysical Society 58^<th> Annual Meeting
  • Place of Presentation: San Francisco(米国)
• [Presentation] Impaired bone formation in Tric-b-knockout mice (2014)
  • Author(s): Zhao C, Yamazaki D, Aoyama F, Iida T, Nishi M, Sawaguchi A, Takeshima H
  • Organizer: Biophysical Society 58^<th> Annual Meeting
  • Place of Presentation: San Francisco(米国)
• [Presentation] H^+ inhibits TRIC-B channels derived from mouse TRIC-A knockout tissue (2014)
  • Author(s): Obrien F, Venturi E, Galfre E, Matyjaszkiewicz A, Yamazaki D, Nishi M, Takeshima H, Stisapesan R
  • Organizer: Biophysical Society 58^<th> Annual Meeting
  • Place of Presentation: San Francisco(米国)
• [Presentation] SR counter-ion channels mediated blood pressure regulation (2014)
  • Author(s): Yamazaki D, Tao S, Takeshima H
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島
• [Presentation] TRIC-A過剰発現による血管弛緩メカニズム (2014)
  • Author(s): 山崎大樹、陶晟辰、竹島浩
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] The MBOAT family protein Mitsugumin 56 contributes to postnatal maturation in the mouscle sarcoplasmic reticulum (2014)
  • Author(s): Bo Van, Miyuki Nishi, Shinji Komazaki, Ki Ho Park, Daiju Yamazaki, Jianjie Ma, Hiroshi Takeshima
  • Organizer: Biophysical Society 58th Annual Meeting
  • Place of Presentation: San Francisco
• [Presentation] Impaired bone formation in Tric-b-knockout mice (2014)
  • Author(s): Chengzhu Zhao, Daiju Yamazaki, Fumiyo Aoyama, Tsunaki Iida, Miyuki Nishi, Akira Sawaguchi, Hiroshi Takeshima
  • Organizer: Biophysical Society 58th Annual Meeting
  • Place of Presentation: San Francisco
• [Presentation] H+ inhibits TRIC-B channels derived from mouse TRIC-A knockout tissue (2014)
  • Author(s): Fiona OBrien, Elisa Venturi, Elena Galfre, Antoni Matyjaszkiewicz, Daiju Yamazaki, Miyuki Nishi, Hiroshi Takeshima, Rebecca Stisapesan
  • Organizer: Biophysical Society 58th Annual Meeting
  • Place of Presentation: San Francisco
• [Presentation] TRIC-A欠損マウスにおけるイソプロテレノール誘発性心臓線維化 (2014)
  • Author(s): 山崎大樹、趙成珠、陶晟辰、王朝弘、西美幸、竹島浩
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
• [Presentation] Hypotension in SM-specific TRIC-A-transgenic mice (2013)
  • Author(s): Tao S, Yamazaki D
  • Organizer: Biophysical Society 57^<th> Annual Meeting
  • Place of Presentation: Philadelphia(米国)
• [Presentation] The role of Ca2+ handling in TRIC knockout neonatal cardiomyocytes (2013)
  • Author(s): Zhao C, Park KH, Naitou D, Wang C, Yamazaki D
  • Organizer: Biophysical Society 57^<th> Annual Meeting
  • Place of Presentation: Philadelphia(米国)
• [Presentation] Co-expression of TRIC-A and cardiac Ryanodine receptor affects store-overload induced calcium release in HEK293 cells (2013)
  • Author(s): Zhou X, Park KH, Lin PH, Yamazaki D
  • Organizer: Biophysical Society 57^<th> Annual Meeting
  • Place of Presentation: Philadelphia(米国)
• [Presentation] TRIC-Aは血管平滑筋においてSRのカルシウム分布を制御する (2013)
  • Author(s): 山崎大樹、陶晟辰、竹島浩
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡
• [Presentation] TRIC-Aの過剰発現による過分極シグナルの亢進は血管を弛緩させる (2013)
  • Author(s): 陶晟辰、山崎大樹、竹島浩
  • Organizer: 第8回トランスポーター研究会
  • Place of Presentation: 熊本
• [Presentation] Facilitated hyperpolarization signaling relaxes vascular smooth muscle in Tric-a-overexpressing mice (2013)
  • Author(s): Yamazaki D
  • Organizer: HDP第2回国際シンポジウム
  • Place of Presentation: 東京
• [Presentation] 平滑筋特異的TRIC-A過剰発現マウスにおける低血圧発症メカニズムの解明 (2013)
  • Author(s): 陶晟辰、山崎大樹、駒崎伸二、趙成珠、飯田綱規、柿澤昌、今泉祐治、竹島浩
  • Organizer: 第123回日本薬理学会近畿部会
  • Place of Presentation: 名古屋
• [Presentation] 平滑筋特異的TRIC-A過剰発現マウスにおける低血圧発症メカニズム (2013)
  • Author(s): 陶晟辰、山崎大樹、竹島浩
  • Organizer: 第63回日本薬学会近畿支部総会・大会
  • Place of Presentation: 京都
• [Presentation] Hypotension in SM-specific TRIC-A-transgenic mice (2013)
  • Author(s): Tao S, Yamazaki D, Nishi M, Ma J, Takeshima H.
  • Organizer: Biophysical Society 57th Annual Meeting
  • Place of Presentation: Philadelphia（アメリカ）
• [Presentation] The role of Ca2+ handling in TRIC knockout neonatal cardiomyocytes (2013)
  • Author(s): Zhao C, Park K-H, Naitou D, Wang C, Yamazaki D, Nishi M, Ma J, Takeshima H.
  • Organizer: Biophysical Society 57th Annual Meeting
  • Place of Presentation: Philadelphia（アメリカ）
• [Presentation] Co-expression of TRIC-A and cardiac Ryanodine receptor affects store-overload induced calcium release in HEK293 cells (2013)
  • Author(s): Zhou X, Park K-H, Lin P-H, Yamazaki D, Pan Z, Chen SR W, Takeshima H, Ma J
  • Organizer: Biophysical Society 57th Annual Meeting
  • Place of Presentation: Philadelphia（アメリカ）
• [Presentation] TRIC-Aは血管平滑筋においてSRのカルシウム分布を制御する (2013)
  • Author(s): 山崎大樹、陶晟辰、竹島浩
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡国際会議場（福岡県）
• [Presentation] TRICチャネルによる血圧調節メカニズム (2012)
  • Author(s): 山崎大樹
  • Organizer: 第7回トランスポーター研究会
  • Place of Presentation: 京都
• [Presentation] 循環機能調節における小胞体カルシウムハンドリング (2012)
  • Author(s): 山崎大樹
  • Organizer: 京都大学学際融合教育研究推進センター生理化学研究ユニットシンポジウム
  • Place of Presentation: 京都
• [Presentation] 血管平滑筋におけるTRIC-Aチャネルによる血圧調節メカニズムの解明 (2012)
  • Author(s): 山崎大樹、陶晟辰、喜多紗斗美、西美幸、今泉祐治、岩本隆宏、竹島浩
  • Organizer: 第26回日本薬学会近畿支部総会・大会
  • Place of Presentation: 兵庫
• [Presentation] 平滑筋特異的TRIC-Aトランスジェニックマウスにおける過分極シグナルの亢進 (2012)
  • Author(s): 山崎大樹、陶晟辰、竹島浩
  • Organizer: 筋生理の集い
  • Place of Presentation: 東京
• [Presentation] TRICチャネルによる血圧調節メカニズム (2012)
  • Author(s): 山崎大樹
  • Organizer: 第7回トランスポーター研究会
  • Place of Presentation: 京都大学（京都府）
  • Invited
• [Presentation] 循環機能調節における小胞体カルシウムハンドリング (2012)
  • Author(s): 山崎大樹
  • Organizer: 京都大学学際融合教育研究推進センター生理化学研究ユニットシンポジウム
  • Place of Presentation: 京都大学（京都府）
• [Presentation] 血管平滑筋におけるTRIC-Aチャネルによる血圧調節メカニズムの解明 (2012)
  • Author(s): 山崎大樹、陶晟辰、喜多紗斗美、内藤大督、西美幸、今泉祐治、岩本隆宏、竹島浩
  • Organizer: 第26回日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学浜甲子園キャンパス（兵庫県）
  • Invited
• [Presentation] 平滑筋特異的TRIC-Aトランスジェニックマウスにおける過分極シグナルの亢進 (2012)
  • Author(s): 山崎大樹、陶晟辰、竹島浩
  • Organizer: 筋生理の集い
  • Place of Presentation: 東京慈恵会医科大学（東京都）
• [Remarks] 研究室ホームページ
  • URL: http://www.pharm.kyoto-u.ac.jp/biochem/