title: Klotho suppresses cardiomyocyte apoptosis in mice with stress-induced cardiac injury via downregulation of endoplasmic reticulum stress.
abstract: Cardiomyocyte apoptosis is a common pathological alteration in heart disease which results in systolic dysfunction or sudden death. Klotho is a novel anti-aging hormone. We tested the effects of klotho on cell apoptosis in isoproterenol-treated cardiomyocytes. In BALB/c mice, cardiac injury was induced by subcutaneous injection of isoproterenol (5 mg/kg, for 9 days, s.c.). Klotho (0.01 mg/kg, every other day for 4 days, i.p.) was administered to determine the changes in isoproterenol-induced apoptosis. Mouse heart was harvested at day 2, day 5, and day 9 after isoproterenol injection. Isoproterenol induced cardiac apoptosis and endoplasmic reticulum (ER) stress in a time-dependent manner. However, klotho partly reversed isoproterenol-induced cardiac apoptosis and ER stress. These same effects were observed in cultured cardiomyocytes. Furthermore, the results also showed that SB203580, a p38 inhibitor, and SP600125, a c-Jun NH2-terminal kinase (JNK) inhibitor, reduced cardiomyocyte apoptosis and ER stress, however, klotho suppressed isoproterenol-induced activation of p38 and JNK. Taken together, these results indicated that cardioprotection by klotho was related to the attenuation of ER stress and ER stress-induced apoptosis, at least partly, through suppressing activation of the p38 and JNK pathway.
authors: Department of Geriatrics, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors: Shuang
authors: S
authors: Song
authors: Pan
authors: P
authors: Gao
authors: Hang
authors: H
authors: Xiao
authors: Yan
authors: Y
authors: Xu
authors: Liang Yi
authors: LY
authors: Si
authors: Lian Yi
authors: LY
authors: Si
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000737:chemistry; D017209:Apoptosis; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000378:metabolism*; D007093:Imidazoles / Q000737:chemistry; D007545:Isoproterenol / Q000737:chemistry; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: D000873:Anthracenes; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; C432165:pyrazolanthrone; D005966:Glucuronidase; D000090265:Klotho Proteins; D007545:Isoproterenol; C093642:SB 203580