Alteration of HIF-1 expression by heart failure and its involvement in cardiomyocyte survival

• Project/Area Number: 19790535
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Sapporo Medical University
• Principal Investigator: YANO Toshiyuki Sapporo Medical University, 医学部, 助教 (40444913)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,530,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥2,100,000 (Direct Cost: ¥2,100,000)
• Keywords: 分子心臓病態学 / 循環器 / 細胞死

Research Abstract

心筋細胞死は、心筋梗塞や高血圧による心不全の主要な原因の一つであるが、不全心において細胞死がもたらされる機序は明らかにされていない。その原因として本研究では、不全心の細胞障害に対して防御的に働くhypoxia inducible factor-1α(HIF-1α)の内因性保護機構の破綻に注目した。その結果、HIF-1αの発現量には不全心と健常心で差がなかったが、ミトコンドリアの酸化ストレス亢進により細胞死への受攻性が亢進しており、HIF-1αの作用で発現するエリスロポエチンの心筋保護効果が消失していることが明らかになった。

Research Products

• [Journal Article] Roles of Cx43-associated protein kinases in suppression of gap junction-mediated chemical coupling by ischemic preconditioning (2009)
  • Author(s): Naitoh K, Yano T, (他8名)
  • Journal Title: Am J Physiol Heart Circ Physiol 296 Pages: 396-403
  • Peer Reviewed
• [Journal Article] Roles of Cx43-associated protein kinases in suppression of gap junction-mediated chemical coupling by ischemic preconditioning (2009)
  • Author(s): Kazuyuki Naitoh
  • Journal Title: American Journal of Physiology-Heart and Ciculatory Physiology 296 Pages: 396-403
  • Peer Reviewed
• [Journal Article] Limitation of infarct size by erythropoietin is associated with translocation of Akt to mitochondria after reperfusion (2008)
  • Author(s): Kobayashi H, Miura T, Ishida H, Miki T, Tanno M, Yano T, (他3名)
  • Journal Title: Clin Exp Pharmacol Physiol 35 Pages: 812-819
  • Peer Reviewed
• [Journal Article] Limitation of infarct size by erythropoietin is associated with translocation of Akt to the mitochondria after reoerfusion (2008)
  • Author(s): Hironori Kobayashi
  • Journal Title: Clinical Experimental Pharmacology and Physiology 35 Pages: 812-819
  • Peer Reviewed
• [Journal Article] Modulation of the mitochondrial permeability transition pore complex in GSK3beta-mediated myocardial protection (2007)
  • Author(s): Nishihara M, Miura T, Miki T, Tanno M, Yano T, (他5名)
  • Journal Title: J Mol Cell Cardiol 43 Pages: 564-570
  • Peer Reviewed
• [Journal Article] Delta-opioid receptor activation before ischemia reduces gap junction permeability in ischemic myocardium by PKC-epsilon-mediated phosphorylation of connexin43 (2007)
  • Author(s): Miura T, Yano T, (他5名)
  • Journal Title: Am J Physiol Heart Circ Physiol 293 Pages: 1425-1431
  • Peer Reviewed
• [Journal Article] Modulation of the mitochondrial permeability pore complex in GSK-3β-mediated mediated myocardial protection (2007)
  • Author(s): Masahiro Nishihara
  • Journal Title: Journal of Molecular and Cellular Cardiology 43 Pages: 564-570
  • Peer Reviewed
• [Journal Article] δ-opioid receptor activation before ischemia reduces gap junction permeability in the ischemis myocardium by PKC-ε-mediated phosphorylation of connexin43 (2007)
  • Author(s): Teysuji Miura
  • Journal Title: American Journal of Physiology-Heart and Ciculatory Physiology 293 Pages: 1425-1431
  • Peer Reviewed
• [Presentation] ROS-mediated enhancement of ANT-cyclophilin D interaction underlies reduced anti-infarct tolerance and lack of response of cardiomyocytes to pro-survival signaling in hypertrophied hearts (2009)
  • Author(s): 矢野俊之
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-21
• [Presentation] ROS-mediated enhancement of ANT-cyclophilin D interaction underlies reduced anti-infarct tolerance and lack of response of c ardiomyocytes to pro-survival signaling in hypertrophied hearts (2009)
  • Author(s): Toshiyuki Yano
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-21
• [Presentation] Distinct roles of PKC-epsilon and p38MAPK in preconditioning-induced modulation of gap junction permeability during ischemia (2009)
  • Author(s): 矢野俊之
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-20
• [Presentation] Distinct roles of PKCe and p38MAPK in preconditioning-induced modulation of gap junction permeability during ischemia (2009)
  • Author(s): Toshiyuki Yano
  • Organizer: 日本循環器学会
  • Place of Presentation: 日本循環器学会
  • Year and Date: 2009-03-20
• [Presentation] 高血圧性肥大心における心筋保護機構破綻の機序 (2008)
  • Author(s): 矢野俊之
  • Organizer: 日本高血圧学会
  • Place of Presentation: 札幌
  • Year and Date: 2008-10-11
• [Presentation] Impairment of myocardial response to erythropoietin-induced protection in hypertensive hypertrophied hearts (2008)
  • Author(s): 矢野俊之
  • Organizer: 日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-28
• [Presentation] Impairment of myocardial response to erythropoietin-induced protection in hypertensive hypertfrolhied hearts (2008)
  • Author(s): Toshiyuki Yano
  • Organizer: 日本循環器学会
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-28
• [Presentation] Suppression of mitochondrial GSK-3β activity by its Ser9-phosphorylation contributes to cardiomyocyte protection afforded by erythropoietin against oxidative stress-induced apoptosis (2007)
  • Author(s): 大堀克彦
  • Organizer: American Heart Association
  • Place of Presentation: Orlando,Florida,USA
  • Year and Date: 2007-11-06
• [Presentation] Suppression of mitochondrial GSK-3β activity by its Ser9-phosphorylation contributes to cardiomyocyte protection afforded by erythropoietin against oxidative stress-induced apoptosis (2007)
  • Author(s): Katsuhiko Ohori
  • Organizer: American Heart Association Scientific Sessions 2007
  • Place of Presentation: Orlando,Florida,USA
  • Year and Date: 2007-11-06