STRESS PROTEINS AND SH-GROUPS IN OXIDANT-INDUCED CELLULAR INJURY AFTER CHRONIC ETHANOL ADMINISTRATION IN RAT

It is generally agreed that lipid peroxides Flay an important role in the pathogenesis of ethanol-induced cellular injury and that free sulf hydryl groups are vital in cellular defense against endogenous or exog enous oxidants. It has been observed that oxidative stress induces the synthesis of the 70-kDa family of heat-shock proteins (HSPs). Inducti on of HSPs represents an essential and highly conserved cellular respo nse to a variety of stressful stimuli. In the present study we measure d in various brain areas and in liver the intracellular levels of HSP7 0 proteins, sulfhydryl groups and the antioxidant enzyme status after chronic administration of mild intoxicating doses of ethanol to rats. Expression of HSP70 in response to alcohol administration was particul arly high in the hippocampus and striatum. In these brain areas, the i ncrease in HSP70 protein levels occurred in absence of significant cha nges of antioxidant enzyme activities and was correlated with a marked depletion of intracellular bound thiols and with a decreased suscepti bility to lipid peroxidation. Lower levels of HSP70 induction were fou nd in cortex and cerebellum and were associated to decreases in SOD an d CAT enzyme activities, with a lower depletion of protein bound thiol s and with an increased susceptibility to lipid peroxidation. This stu dy agrees with our previous results performed on acute alcohol intoxic ation and supports the hypothesis that HSP70 induction protects the di fferent brain areas against oxidative stress. (C) 1998 Elsevier Scienc e Inc.