New therapeutic approach of myofibrillar myopathy by mitochondrial protection

• Project/Area Number: 25460105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pharmacology in pharmacy
• Research Institution: Iwate Medical University
• Principal Investigator: Sanbe Atsushi 岩手医科大学, 薬学部, 教授 (30425706)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 心筋症 / 熱ショックタンパク質 / ストレス / アポトーシス / 心不全 / ミオパシー / ストレスタンパク質 / ミトコンドリア / 熱ショックストレスタンパク質

Outline of Final Research Achievements

It is hypothesized that BCL-2 associated athanogene (BAG) 3 can play an important role in cytoprotective effect of BCL-2, antiapoptotic factor, by direct protein-protein interaction. We examined changes in BAG3 level in myocardium in myofibrilallar myopathy (MFM) mouse model. In MFM mouse heart, marked increase in BAG3 level was detected. In order to analyze the role of BAG3 in cardiomyocytes, knockdown approach using si-RNA targeting to BAG3 was performed. The knockdown of BAG3 enhanced apoptotic cell death in cardiomyocytes. These results suggest that BAG3 may play a protective role in cardiomyocytes.

Research Products

• [Journal Article] Upregulation of Inorganic pyrophosphatase 1 in hypothyroid embryonic chick cerebellum. (2015)
  • Author(s): 100)Tezuka Y., Herai N., Inomata Y., Kagami K., Yamauchi J., Nishigori H. and Sanbe A.
  • Journal Title: Life Sciences Volume: 128 Pages: 94-100
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 神経系におけるBCL2関連athanogene 3の機能的役割 (2015)
  • Author(s): 11)猪俣結衣
  • Organizer: 第658回岩手医学会例会
  • Place of Presentation: 神戸
  • Year and Date: 2015-05-20
• [Presentation] 大学院生シンポジウム GS01 循環器疾患に関した新規病態病態制御メカニズムメカニズム-心血管疾患をターゲットとした薬学基礎研究の現状と治療への展望- 「神経筋疾患におけるBCL2関連athanogene 3の機能的役割」 (2015)
  • Author(s): 猪俣結衣、日野千鶴、手塚優、東尾里英子、青柳利紀、三部篤
  • Organizer: 第135回日本薬学会年会
  • Place of Presentation: 神戸
  • Year and Date: 2015-03-26 – 2015-03-30
  • Invited
• [Presentation] Histon deacetylase (HDAC) 6 in cardiac disease. Symposium 1S07 Cardiac Disease-Regenerative Medicine and Drug Development (2014)
  • Author(s): Sanbe Atsushi
  • Organizer: 第87回日本生化学会年会
  • Place of Presentation: 京都
  • Year and Date: 2014-10-15 – 2014-10-18
  • Invited
• [Presentation] ストレスタンパク質と心疾患 (2014)
  • Author(s): 三部篤
  • Organizer: 第134回日本薬学会年会
  • Place of Presentation: 熊本
  • Invited
• [Presentation] Protein Folding Disease and ATP-sensitive Potassium Channels (2014)
  • Author(s): 三部篤
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
  • Invited
• [Presentation] 低分子ストレスタンパク質によって引き起こされる心臓疾患 (2014)
  • Author(s): 三部篤
  • Organizer: 生体機能と創薬誌ポジウム2013
  • Place of Presentation: 福岡
  • Invited
• [Presentation] Cardioprotective effect of nicorandil, a mitochondrial potassium channel opener, via modification of mitochondrial permeability transition pore in myofibrilar myopathy. (2014)
  • Author(s): Aoyagi T., Yamatoya Y., Natsusaka K., Tezuka Y., Sanbe A.
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
• [Presentation] アミロイドと心不全 (2013)
  • Author(s): 三部篤
  • Organizer: 第23回日本循環薬理学会
  • Place of Presentation: 福岡
  • Invited
• [Remarks] 岩手医科大学薬学部薬剤治療学講座
  • URL: http://gaia-sb.iwate-med.ac.jp/pharm/?page_id=49