Heat Stress Induces Extended Plateau of Hsp70 Accumulation--A Possible Cytoprotection Mechanism in Hepatic Cells

J Cell Biochem. 2015 Oct;116(10):2365-74. doi: 10.1002/jcb.25187.


The relevance of heat preconditioning resides in its ability to protect cells from different kinds of injury by induction of heat shock proteins, a process in which the intensity of heat stress (HS) and duration of subsequent recovery are vital. This study evaluates the effects of moderate HS (45 min/43°C) and the time-dependent changes during recovery period of HSP70, Bcl-2 and p53 gene and protein expression in HepG2 cells. We also evaluated the effects of 0.4 mM aspirin (ASA) as a potential pharmacological co-inducer of HSP, both alone and in a combination with HS (ASA + HS). HS alone and ASA + HS caused a major up-regulation of HSP70 mRNA in the first 2 h, while HSP70 protein increased gradually and was especially abundant from 2 h to 24 h. Regarding Bcl-2, all treatments rendered similar results: gene expression was down-regulated in the first 2 h, after which there was protein elevation (12-48 h after HS). mRNA expression of p53 in HS- and (ASA + HS)-cells was down-regulated in the first 12 h. The immediate decrease of p53 protein after HS was followed by a biphasic increase. In conclusion, 0.4 mM ASA + HS does not act as a co-inducer of HSP70 in HepG2 cells, but promotes Bcl-2 protein expression during prolonged treatment. Our suggestion is that hepatic cells are most vulnerable in the first 2-6 h, but may have a high capacity for combating stress 12-24 h after HS. Finally, short-term exposure HS might be a "physiological conditioner" for liver cells to accumulate HSP and Bcl-2 proteins and thus obtain cytoprotection against an additional stress.


Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspirin / administration & dosage
  • Cytoprotection / genetics
  • Gene Expression Regulation / drug effects
  • HSP70 Heat-Shock Proteins / biosynthesis*
  • HSP70 Heat-Shock Proteins / genetics
  • Heat-Shock Response / genetics*
  • Hep G2 Cells
  • Hepatocytes / metabolism
  • Hot Temperature
  • Humans
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA, Messenger / biosynthesis
  • Tumor Suppressor Protein p53 / biosynthesis*
  • Tumor Suppressor Protein p53 / genetics


  • HSP70 Heat-Shock Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Aspirin