罗格列酮改善胰岛素抵抗大鼠海马Alzheimer病样tau蛋白磷酸化水平  

Rosiglitazone Ameliorate Alzheimer-like Hyperphosphorylation of tau Protein in The Hippocampus of Rats With Insulin Resistance

作　　者：胡蜀红[1] 杨雁[1] 张建华[1] 张木勋[1] 龚成新[2,3] 

机构地区：[1]华中科技大学同济医学院附属同济医院内分泌科 [2]Department of Neurochemistry,New York State Institute for Basic Research in Developmental Disabilities [3]华中科技大学同济医学院病理生理系,武汉430030

出　　处：《生物化学与生物物理进展》2007年第5期533-537,共5页Progress In Biochemistry and Biophysics

摘　　要：Tau蛋白过度磷酸化是Alzheimer病(AD)发病的关键事件.由于2型糖尿病是AD的风险因子,并且胰岛素抵抗是2型糖尿病的特征,检测了胰岛素抵抗大鼠大脑海马tau蛋白磷酸化水平,以及运用胰岛素增敏剂罗格列酮(TZD)后磷酸化的变化,发现胰岛素抵抗组大鼠海马tau蛋白呈过度磷酸化改变,但运用TZD后,tau蛋白的磷酸化状态有所恢复.由于糖原合成激酶-3β(GSK-3β)位于胰岛素信号转导途径中,并且是tau蛋白的重要磷酸激酶,研究检测罗格列酮干预前后GSK-3β活性,发现均升高.研究结果表明,肥胖时胰岛素抵抗导致细胞内胰岛素信号转导途径中,GSK-3β活性上调可能是引起大鼠海马内tau蛋白过度磷酸化的一个重要原因;虽然TZD可抑制tau蛋白的过度磷酸化,但可能不是通过下调GSK-3β活性的途径.Abnormally hyperphosphorylation of tau plays a critical role in the pathogenesis of Alzheimer disease （AD）. Type 2 diabetes whose character is insulin resistance is a known factor of AD. Tan protein were found to be hyperphosphorylated at several AD-related phosphorylation sites （Ser199, Thr212, Ser214, Ser396 and Ser422） in insulin resistant rats. TZD treatment reduced hyperphosphorylation of Ser199, Thr212, Ser396 and Ser422 of tau significantly and of Ser214 of tau to the control level. The activity of GSK-313 was found to be increased dramatically in the hippocampi before and after TZD treatment. These findings suggest （1） that insulin resistance induced by obesity causes a downregulation of insulin signal transduction and the consequent upregulation of GSK-3β activity, which leads to hyperphosphorylation of tau protein, and （2） that rosiglitazone can partially reverse insulin resistance induced tau hyperphosphorylation, which may not mediated by inhibition of GSK-3β activity.

关 键 词：胰岛素抵抗 TAU蛋白 罗格列酮 蛋白磷酸化 糖原合成酶激酶-3Β 

分 类 号：R587.1[医药卫生—内分泌]