Sultana Rukhsana, Bhupanapadu Sunkesula Solomon Raju, Sharma Varsha, Reddanna Pallu, Babu Phanithi Prakash
Department of Animal Sciences, School of Life Sciences, University of Hyderabad, India.
Alcohol. 2005 Jan;35(1):57-66. doi: 10.1016/j.alcohol.2004.12.004.
Hepatic tissue damage induced by chronic exposure to alcohol is mediated through acetaldehyde and associated with reactive oxygen species, which impair cellular defense mechanisms. Because glutathione S-transferases (GSTs) play an important role in the detoxification of xenobiotics and reactive oxygen species, the current study was undertaken to test the effect of alcohol administration on structural and functional characteristics of rat (r) liver Alpha class rGSTs. Western blot analysis revealed an appreciable change in the expression of rGSTA3 subunit levels, whereas no change was observed in activity after chronic alcohol treatment. Reverse-phase high performance liquid chromatographic analysis of rat liver GSTs that were affinity purified with glutathione showed a 1.07-fold increase in rGSTA3 subunit levels in rats treated with alcohol chronically. In addition, liquid chromatographic-electrospray ionization mass spectrometric analysis of GSTs that were affinity purified with glutathione showed the formation of acetaldehyde adducts to the rGSTA3 subunit. Given the abundant expression of rGSTA3 subunit and acetaldehyde adduct formation, results of the current study support the suggestion that modification of rGSTA3 subunit, and thus its impaired function, in alcohol-exposed rats may contribute to the progression of alcohol-induced liver damage.
长期接触酒精所诱导的肝组织损伤是通过乙醛介导的，并与活性氧有关，活性氧会损害细胞防御机制。由于谷胱甘肽S-转移酶（GSTs）在异源生物和活性氧的解毒过程中发挥重要作用，因此开展了本研究以测试给予酒精对大鼠肝脏α类rGSTs的结构和功能特性的影响。蛋白质免疫印迹分析显示，慢性酒精处理后，rGSTA3亚基水平的表达有明显变化，而活性未观察到改变。用谷胱甘肽亲和纯化的大鼠肝脏GSTs的反相高效液相色谱分析显示，长期给予酒精的大鼠中rGSTA3亚基水平增加了1.07倍。此外，用谷胱甘肽亲和纯化的GSTs的液相色谱-电喷雾电离质谱分析显示，rGSTA3亚基形成了乙醛加合物。鉴于rGSTA3亚基的丰富表达和乙醛加合物的形成，本研究结果支持以下观点：在酒精暴露的大鼠中，rGSTA3亚基的修饰及其功能受损可能有助于酒精性肝损伤的进展。
