Induction of the 72-kilodalton heat shock protein and protection from ultraviolet B–induced cell death in human keratinocytes by repetitive exposure to heat shock or 15-deoxy-Δ12,14-prostaglandin J2

Abstract

It has been demonstrated that hyperthermia protects keratinocytes from ultraviolet B (UVB)-induced cell death in culture and in vivo. This effect is mediated by the antiapoptotic effect of heat shock proteins that are transiently induced after exposure to heat at sublethal temperatures. Consequently, induction of Hsp has been proposed as a novel means of photoprotection. However, in the face of daily UVB exposure of human skin in vivo, this approach would not be useful if keratinocytes become less sensitive to Hsp induction with repeated exposure to the inducing agent. The aim of this study was to investigate whether repeated exposure to hyperthermia or to the stress protein activating cyclopentenone prostaglandin 15-deoxy-⌬ 12,14 -prostaglandin J 2 (15dPGJ 2 ) leads to adaptation of the cells, attenuation of the heat shock response, and abrogation of the protective effect. Normal human epidermal keratinocytes (NHEK) and the carcinoma-derived cell line A431 were exposed to either 42ЊC or to 15dPGJ 2 for 4 hours at 24-hour intervals for 4 consecutive days. The intracellular level of the 72-kDa heat shock protein (Hsp72) was determined by enzyme-linked immunosorbent assay (ELISA). Cells were exposed to UVB from a metal halide source after the last heat or 15dPGJ 2 treatment, and survival was determined 24 hours after exposure by a MTT assay. Our results demonstrate that (1) heat shock and 15dPGJ 2 are potent inducers of Hsp72 expression and lead to increased resistance to UVB-induced cell death in human keratinocytes; (2) re-exposure to heat shock leads to a superinduction without attenuation of the absolute increase in Hsp72 and of its UVB-protective effect; (3) the UVB tolerance induced by 15dPGJ 2 is enhanced by repeated exposure without a further increase of Hsp72; (4) repeated heat shock and 15dPGJ 2 up to a concentration of 1 g/mL have no influence on cell growth over a period of 4 days. We conclude that through repeated exposure to Hsp-inducing factors, stress tolerance can be maintained without additional toxicity in human keratinocytes. These results provide a basis for the development of nontoxic Hsp inducers that can be repeatedly applied without loss of effect.

Overexpression of human selenoprotein H in neuronal cells ameliorates ultraviolet irradiation-induced damage by modulating cell signaling pathways

“…Therefore, HSP40 determines the activity of HSP70s. Upregulation of HSP70s with heat treatment or stress protein activators protected human keratinocytes from subsequent UVB-induced damage (Merwald et al, 2006; Trautinger et al, 1995, 1996) and neurons from hypoxic/ischemic injuries (Giffard et al, 2004; Yenari et al, 2005; Zhao et al, 2008). UVB is capable of inducing HSP70s; however, there has been no report available on the effects of UVB-treatment and SelH on HSP40.…”

Influence of heat stress on human monocyte-derived dendritic cell functions with immunotherapeutic potential for antitumor vaccines

“…As it has been described that repetitive exposure to heat shock protects cells from apoptosis [13], we tested the effect of heat stress on the apoptosis of DC induced by GM-CSF and IL-4 deprivation (Fig. 6).…”

The topical antimicrobial zinc pyrithione is a heat shock response inducer that causes DNA damage and PARP-dependent energy crisis in human skin cells

“…Research from various groups, including our own, has shown that small molecule inducers of the heat shock and Nrf2 (nuclear factor-E2-related factor 2) oxidative stress response pathways exert chemopreventive activity with suppression of skin cell photodamage, photooxidative stress, and photocarcinogenesis (Dinkova-Kostova et al 2006;Merwald et al 2006;Wondrak et al 2008).…”