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Involvement of Heat‐Shock Protein 70 and P53 Proteins in Attenuation of UVC‐lnduced Apoptosis by Thermal Stress in Hepatocellular Carcinoma Cells
Author(s) -
Chen YenChou,
LinShiau ShoeiYn,
Lin JenKun
Publication year - 1999
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1999.tb01952.x
Subject(s) - transfection , apoptosis , heat shock protein , hsp70 , microbiology and biotechnology , dna damage , dna fragmentation , cell culture , programmed cell death , chemistry , biology , dna , gene , biochemistry , genetics
— Induction of apoptosis is a function of external stimuli and cellular gene expression. Many cells respond to DNA damage by the induction of apoptosis, which depends on a functional p53 protein and is signaled by elevation of p53 levels. In this study, we found that a prior exposure to mild stress (42 A° C) can protect HepG2 (p53+/+) ceUs from a subsequent UVC‐induced apoptosis determined by DNA fragmentation and ratio of sub‐Gl peak, but no heat‐enhanced protection was found in Hep3B (p53 ‐/‐ ) cells. Although a similar inductive pattern of HSP70 protein and mRNA was detected in the two cell lines under thermal stress, the effect of thermal stress on UVC‐induced apoptosis in HepG2 and Hep3B cells was obviously different. Overexpression of HSP70 by transient trans‐fection of HSP70 expression vector in HepG2 cells significantly inhibited UVC‐induced cell death; however, this inhibitory effect did not occur in transfected‐Hep3B cells. Treatment of HepG2 cells with p53‐specific anti‐sense oligonucleotide could effectively block the antiapo‐ptotic effect of thermal stress on UVC‐induced apoptosis and increase of intracellular wild‐type p53 protein by transfecting wtp53 expression plasmid into Hep3B cells yielded more resistance to UVC irradiation after prior thermal stress exposure. The results reveal an involvement of p53 in the antiapoptotic effect of thermal stress on UVC irradiation. Finally, a p53 protein increase was detected in UVC‐treated HepG2 cells and could be coim‐munoprecipitated with HSP70 after a thermal stress treatment Prolonged p53 binding activity and enhanced expression of p53‐controlled genes such as Gl arrest and DNA damage 45 and wild‐type p53 activation factor 1/ Cdk‐interacting protein 1 by thermal stress are also observed in UVC‐irradiated HepG2 cells. Based on these results, we propose that the antiapoptotic effect of thermal stress is mediated by increasing HSP70 and modulating intracellular p53 function.