Overexpression of HSP70 prevents ultraviolet B-induced apoptosis of a human melanoma cell line

Abstract

The heat shock response is a highly conserved reaction common to all cells and organisms. It has been reported that hyperthermic treatment can induce the expression of the heat shock protein (HSP) and can protect cells from ultraviolet (UV) B radiation. In this study, we evaluated the effects of induced HSP70 on resistance to UV radiation. G361 amelanotic human melanoma cells were irradiated with increasing doses of UVB. UVB irradiation caused apoptotic cell death in these cells. Following transfection with MFG.hsp70.puro plasmid, the expression of HSP70 was determined. Compared to control vector-transfected cells, hsp70-transfected cells showed significantly elevated levels of HSP70 and were highly resistant to UVB irradiation. In order to investigate the effects of HSP70 on the apoptotic pathway, the changes in caspase-3 and PARP were analyzed. Following UVB irradiation, activation of caspase-3 and cleavage of PARP were observed in control vector-transfected cells, and the changes in these molecules were inhibited in the hsp70-transfected cells. These results suggest that UVB-induced apoptosis of melanoma cells is accompanied by caspase-3 activation and PARP cleavage, which can be prevented by an overexpression of HSP70.

Apoptosis and melanoma chemoresistance

“…In melanoma, Hsp70 was shown to be upregulated in a subset of primary tumors and cell lines (Dressel et al, 1998;Ricaniadis et al, 2001). The extent to which Hsp70 contributes to melanoma chemoresistance in vivo is unknown, but melanoma cells overexpressing Hsp70 have a higher resistance to UV irradiation (Park et al, 2000).…”

Death penalty for keratinocytes: apoptosis versus cornification

“…104,105 These two heat-shock proteins are both able to inhibit the apoptosome formation, 106,107 and hsp70 can also antagonize the proapoptotic effects of apoptosis-inducing factor. 108 Overexpression of hsp70 can prevent UVB-induced apoptosis in an epidermal carcinoma line, 109 and hsp70-deficient mice are more susceptible to UVB-induced apoptosis. 110 Taken together, these observations may reflect the presence of strong antiapoptotic mechanisms, which may protect keratinocytes from environmental stress-induced apoptosis.…”

Spermatocyte-specific expression of constitutively active heat shock factor 1 induces HSP70i-resistant apoptosis in male germ cells

“…14 In fact, different HSPs can interfere with both anti-and proapoptotic pathways (reviewed in Beere 8 and Sreedhar and Csermely 9 ). Numerous studies, however, have shown that overexpression of HSP70, in either transgenic mice or transfected cells, can protect different somatic cells from apoptotic death induced not only by the hyperthermia 15 but also by other stimuli, including ischemia, 16 nitric oxide, 17 adriamycin, 18 UV-B radiation 19 or pathogenic viruses. 20 Two members of the HSP family are expressed normally under non-heat shock conditions specifically during spermatogenesis.…”