Cathepsin B is involved in the heat shock induced cardiomyocytes apoptosis as well as the anti-apoptosis effect of HSP-70
Cathepsin B is involved in the heat shock induced cardiomyocytes apoptosis as well as the anti-apoptosis effect of HSP-70
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DOI：
10.1007/s10495-014-1033-9
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发表时间：
2014-11-01
期刊：
影响因子：
7.2
通讯作者：
Lin, Cheng-Hsien
中科院分区：
文献类型：
--
作者：
Hsu, Shu-Fen;Hsu, Chuan-Chih;Lin, Cheng-Hsien
组织蛋白酶B是一种主要的溶酶体半胱氨酸蛋白酶，在细胞凋亡中起重要作用。在此，我们研究了组织蛋白酶B是否参与了热损伤(HI)引起的心肌细胞凋亡，热休克蛋白(HSP)-70对热损伤(HI)诱导的心肌细胞凋亡具有保护作用。H9C2细胞在43℃循环水浴中孵育120min产生HSP-70，而H9C2细胞在HI开始前8h通过微热预处理(或将其置于42℃水浴30min)预诱导产生HSP-70。结果发现，HI可引起H9C2细胞的心肌细胞凋亡和组织蛋白酶B活性升高。E--c除降低组织蛋白酶B活性外，还能显著抑制缺氧诱导的H9C2细胞凋亡(表现为细胞凋亡率增加，细胞色素C增加，caspase-9/-3增加，bcl2/bax降低)。此外，轻度热预处理诱导的HSP-70和Tripolde抑制HSP-70的作用分别显著减弱或加重H9C2细胞的心肌细胞凋亡和组织蛋白酶B活性。此外，雷公藤内酯醇预适应可明显降低HSP-70诱导的心肌细胞凋亡和组织蛋白酶B活性升高的效应。这些结果表明，组织蛋白酶B参与了缺氧缺血诱导的H9C2细胞的心肌细胞凋亡，HSP-70通过组织蛋白酶B途径保护H9C2细胞免受缺氧诱导的心肌细胞凋亡。
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 A degrees 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 A degrees 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.