title: Protective effect of geranylgeranylacetone via enhanced induction of HSPB1 and HSPB8 in mitochondria of the failing heart following myocardial infarction in rats.
abstract: The mechanisms underlying mitochondrial impairment in the failing heart are not yet clear. In a previous study, we found that the levels of small heat shock proteins (HSP) such as mitochondrial HSPB1 and HSPB8 in the failing heart following myocardial infarction were decreased. In the present study, to verify the hypothesis that mitochondrial dysfunction in the failing heart is associated with alterations in mitochondrial small heat shock proteins, we examined the effects of geranylgeranylacetone, a heat shock protein inducer, on the cardiac mitochondrial function after myocardial infarction. When hemodynamic parameters of rats with myocardial infarction were measured at the 8th (8W) week after coronary artery ligation (CAL), the 8W-CAL showed signs of chronic heart failure concomitant with a reduced mitochondrial oxygen consumption rate. HSPB1 and HSPB8 contents in the mitochondrial fraction prepared from the failing heart were decreased, suggesting that an attenuation of mitochondrial translocation of HSPB1 and HSPB8 had led to an impairment of mitochondrial energy-producing ability. Geranylgeranylacetone treatment from the 2nd to 8th week after myocardial infarction attenuated the reduction in mitochondrial HSPB1 and HSPB8 contents. Furthermore, the mitochondrial energy-producing ability and cardiac pump function were preserved by orally administered geranylgeranylacetone during the development of heart failure. These results suggest that the induction of small heat shock proteins in the infarcted heart by geranylgeranylacetone treatment contributed to the preservation of mitochondrial function, leading to an improvement of cardiac contractile function.
authors.affiliation: Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Marunouchi
authors.affiliation: Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Inomata
authors.affiliation: Department of Pharmacotherapeutics, School of Pharmacy, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Siwa, Iwate 028-3603, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sanbe
authors.affiliation: Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Takagi
authors.affiliation: Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. Electronic address: tanonaka@toyaku.ac.jp.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Tanonaka
mesh_terms: D000818:Animals; D019610:Cytoprotection / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006333:Heart Failure / Q000150:complications* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009203:Myocardial Infarction / Q000150:complications*; D009929:Organ Size / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014022:Tissue Survival / Q000187:drug effects
chemical_list: D004224:Diterpenes; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C490753:HspB8 protein, rat; C486114:Hspb1 protein, rat; D017382:Reactive Oxygen Species; C031049:geranylgeranylacetone
keywords: Chronic heart failure: small heat shock protein; Geranylgeranylacetone; Mitochondria; Myocardial infarction