title: Cathepsin B is involved in the heat shock induced cardiomyocytes apoptosis as well as the anti-apoptosis effect of HSP-70.
abstract: Cathepsin B is one of the major lysosomal cysteine proteases that plays an important role in apoptosis. Herein, we investigated whether Cathepsin B is involved in cardiomyocyte apoptosis caused by hyperthermic injury (HI) and heat shock protein (HSP)-70 protects these cells from HI-induced apoptosis mediated by Cathepsin. HI was produced in H9C2 cells by putting them in a circulating 43 °C water bath for 120 min, whereas preinduction of HSP-70 was produced in H9C2 cells by mild heat preconditioning (or putting them in 42 °C water bath for 30 min) 8 h before the start of HI. It was found that HI caused both cardiomyocyte apoptosis and increased Cathepsin B activity in H9C2 cells. E-64-c, in addition to reducing Cathepsin B activity, significantly attenuated HI-induced cardiomyocyte apoptosis (evidenced by increased apoptotic cell numbers, increased tuncated Bid (t-Bid), increased cytochrome C, increased caspase-9/-3, and decreased Bcl-2/Bax) in H9C2 cells. In addition, preinduction of HSP-70 by mild heat preconditioning or inhibition of HSP-70 by Tripolide significantly attenuated or exacerbated respectively both the cardiomyocyte apoptosis and increased Cathepsin B activity in H9C2 cells. Furthermore, the beneficial effects of pre-induction of HSP-70 by mild heat production in reducing both cardiomyocyte apoptosis and increased Cathepsin B activity caused by HI can be significantly reduced by Triptolide preconditioning. These results indicate that Cathepsin B is involved in HI-induced cardiomyocyte apoptosis in H9C2 cells and HSP-70 protects these cells from HI-induced cardiomyocyte apoptosis through Cathepsin B pathways.
authors.affiliation: Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Hsu
authors.forename: Chuan-Chih
authors.initials: CC
authors.lastname: Hsu
authors.forename: Bor-Chih
authors.initials: BC
authors.lastname: Cheng
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism*; D002460:Cell Line; D004224:Diterpenes / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018869:Heat-Shock Response; D006358:Hot Temperature; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology; D051381:Rats
chemical_list: D051017:Apoptosis Regulatory Proteins; D004224:Diterpenes; D004852:Epoxy Compounds; D018840:HSP70 Heat-Shock Proteins; D010616:Phenanthrenes; C001899:triptolide; D002401:Cathepsin B