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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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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.

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Acknowledgments

This study was funded in part by a National Science Council of the Republic of China (Taipei, Taiwan, ROC) (NSC 99-2314-B-384-006- MY2; NSC 99-2314-B-384-004-MY2), and supported in part by a faculty research grant of Chi Mei Medical Center (CMH-103-5). We would like to thank three anonymous reviewers and the editor for their comments.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Nursing, Shu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan

    Shu-Fen Hsu

  2. Division of Cardiovascular Surgery, Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

    Chuan-Chih Hsu

  3. Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan

    Bor-Chih Cheng

  4. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan

    Bor-Chih Cheng

  5. Meridigen Biotech Co., Ltd., Taipei, Taiwan

    Cheng-Hsien Lin

  6. Department of Leisure, Recreation, and Tourism Management, Southern Taiwan University, Tainan, Taiwan

    Cheng-Hsien Lin

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  1. Shu-Fen Hsu
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  2. Chuan-Chih Hsu
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  3. Bor-Chih Cheng
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  4. Cheng-Hsien Lin
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Correspondence to Bor-Chih Cheng or Cheng-Hsien Lin.

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Hsu, SF., Hsu, CC., Cheng, BC. et al. Cathepsin B is involved in the heat shock induced cardiomyocytes apoptosis as well as the anti-apoptosis effect of HSP-70. Apoptosis 19, 1571–1580 (2014). https://doi.org/10.1007/s10495-014-1033-9

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