Hsp70 suppresses apoptosis of BRL cells by regulating the expression of Bcl-2, cytochrome C, and caspase 8/3

In Vitro Cell Dev Biol Anim. 2016 May;52(5):568-75. doi: 10.1007/s11626-016-0005-5. Epub 2016 Mar 11.

Abstract

During cold stress, liver cells undergo apoptotic injury as a result of oxidative stress. Heat shock 70 kDa protein (Hsp70) is a protein involved in modulating a variety of physiological processes, including stress responses, proliferation, and apoptosis. In addition, Hsp70 regulates apoptotic signaling pathways in different manners, promoting or suppressing apoptosis. In this study, we investigated the effects of Hsp70 overexpression on hydrogen peroxide (H2O2)-induced apoptosis of Buffalo rat liver (BRL) cells and the underlying mechanisms of these effects. Our results show that in comparison with the control group, Hsp70 overexpression displayed increased protein levels of Bcl-2, and decreased cytochrome c (Cyt c), cleaved caspase 3, and cleaved caspase 8, but no apparent differences were found in levels of Bax. Furthermore, Hsp70 overexpression significantly suppresses the amount of apoptotic cells. Such findings indicate that overexpression of Hsp70 inhibits H2O2-mediated activation of caspase 8 and caspase 3, upregulates the expression of Bcl-2 which is a known anti-apoptotic protein, and decreases the release of Cyt c from the mitochondria into the cytoplasm, collectively decreasing cell apoptosis.

Keywords: Apoptosis; Hsp70; Oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / genetics
  • Caspase 3 / metabolism*
  • Caspase 8 / genetics
  • Caspase 8 / metabolism*
  • Cold-Shock Response
  • Cytochromes c / genetics
  • Cytochromes c / metabolism*
  • Gene Expression Regulation
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism
  • HSP70 Heat-Shock Proteins / physiology*
  • Hydrogen Peroxide / pharmacology
  • Liver / cytology
  • Mitochondria / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Rats, Inbred BUF
  • bcl-2-Associated X Protein / metabolism

Substances

  • HSP70 Heat-Shock Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Cytochromes c
  • Hydrogen Peroxide
  • Caspase 3
  • Caspase 8