Calabrese V, Renis M, Calderone A, Russo A, Reale S, Barcellona M L, Rizza V
Institute of Biochemistry, University of Catania, Italy.
Free Radic Biol Med. 1998 May;24(7-8):1159-67. doi: 10.1016/s0891-5849(97)00441-3.
It is generally agreed that lipid peroxides play an important role in the pathogenesis of ethanol-induced cellular injury and that free sulfhydryl groups are vital in cellular defense against endogenous or exogenous oxidants. It has been observed that oxidative stress induces the synthesis of the 70-kDa family of heat-shock proteins (HSPs). Induction of HSPs represents an essential and highly conserved cellular response to a variety of stressful stimuli. In the present study we measured in various brain areas and in liver the intracellular levels of HSP70 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 particularly high in the hippocampus and striatum. In these brain areas, the increase in HSP70 protein levels occurred in absence of significant changes of antioxidant enzyme activities and was correlated with a marked depletion of intracellular bound thiols and with a decreased susceptibility to lipid peroxidation. Lower levels of HSP70 induction were found in cortex and cerebellum and were associated to decreases in SOD and CAT enzyme activities, with a lower depletion of protein bound thiols and with an increased susceptibility to lipid peroxidation. This study agrees with our previous results performed on acute alcohol intoxication and supports the hypothesis that HSP70 induction protects the different brain areas against oxidative stress.
人们普遍认为，脂质过氧化物在乙醇诱导的细胞损伤发病机制中起重要作用，并且游离巯基在细胞抵御内源性或外源性氧化剂方面至关重要。据观察，氧化应激会诱导70 kDa热休克蛋白（HSPs）家族的合成。HSPs的诱导代表了细胞对各种应激刺激的一种基本且高度保守的反应。在本研究中，我们对大鼠长期给予轻度中毒剂量的乙醇后，测量了其不同脑区和肝脏中HSP70蛋白的细胞内水平、巯基以及抗氧化酶状态。海马体和纹状体中，HSP70对酒精给药的反应表达特别高。在这些脑区，HSP70蛋白水平的增加发生在抗氧化酶活性无显著变化的情况下，并且与细胞内结合巯基的显著消耗以及脂质过氧化敏感性降低相关。在皮质和小脑中发现较低水平的HSP70诱导，并且与超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性降低、蛋白结合巯基消耗减少以及脂质过氧化敏感性增加有关。本研究与我们之前关于急性酒精中毒的结果一致，并支持HSP70诱导可保护不同脑区免受氧化应激的假说。
