Induction of heat shock protein synthesis in human skin fibroblasts in response to oxidative stress: Regulation by a natural antioxidant from rosemary extract

Reactive oxygen species have been implicated in the pathogenesis of the sev ere connective tissue damage present in several photodermatologic disorders , including drug-induced phototoxicity, porphyrias and photoaging. Oxidativ e stress has been shown to alter the expression of mammalian antioxidant en zymes and to enhance numerous transcription factors, including nuclear fact or-kappaB, stress-activated protein kinase and heat shock factor. The latte r represents the transcription factor for the synthesis of cytoprotective p roteins called heat shock proteins. In this study, we investigated the role of oxidative stress and sulfhydryl (SH) groups in the induction of HSP70 i n human skin fibroblasts and the effect of antioxidants. We found that sign ificant HSP70 induction occurred after exposure to HOOH and this was associ ated with marked perturbation in protein and nonprotein SH groups and with a considerable increase in protein carbonyl levels. Treatment with a natura l antioxidant from rosemary extract provided notable protection against str ess-induced modifications of cellular SH and carbonyl content, maintaining functional levels of cytoprotective heat shock protein 70. Our results poin t to the possible involvement of redox mechanisms in the heat shock signal transduction pathway, which may play an important regulatory role in the ge netic mechanisms of tolerance to oxidative stress. Exogenous supplementatio n of an antioxidant hydrophilic extract from rosemary could have cosmetic b enefits and may represent an efficient tool to minimize free radical-induce d skin damage.