Kindy M S
Department of Biochemistry, University of Kentucky, Lexington 40536-0084.
J Cereb Blood Flow Metab. 1993 May;13(3):372-7. doi: 10.1038/jcbfm.1993.50.
Protein tyrosine phosphorylation plays an important role in the regulation of neuronal function. We examined the effects of inhibition of tyrosine phosphorylation on ischemic neuronal damage in the CA1 region of the hippocampus. In the gerbil hippocampus, genistein and lavendustin A, tyrosine kinase inhibitors, were administered 30 min before initiation of 5-min ischemia and reperfusion. Both genistein and lavendustin A blocked tyrosine phosphorylation and prevented delayed neuronal death (DND). However, genistein, an inactive analogue of genistein, did not block DND. Genistein was dose-dependent in the inhibition of DND after ischemia and reperfusion. Administration of genistein 5 to 10 min after ischemia and reperfusion was ineffective in blocking DND in the CA1 region of the hippocampus. The tyrosine kinase inhibitors selectively blocked the phosphorylation of microtubule-associated protein (MAP)-2 kinase following ischemia and reperfusion injury. These results suggest that tyrosine phosphorylation in the ischemic brain is important for neuronal injury and that MAP-2 kinase may play a role in the onset of delayed neuronal death.
蛋白质酪氨酸磷酸化在神经元功能调节中起重要作用。我们研究了抑制酪氨酸磷酸化对海马CA1区缺血性神经元损伤的影响。在沙鼠海马中，酪氨酸激酶抑制剂染料木黄酮和拉文杜斯汀A在5分钟缺血和再灌注开始前30分钟给药。染料木黄酮和拉文杜斯汀A均能阻断酪氨酸磷酸化并预防迟发性神经元死亡（DND）。然而，染料木黄酮的无活性类似物则不能阻断DND。染料木黄酮在缺血和再灌注后对DND的抑制呈剂量依赖性。在缺血和再灌注后5至10分钟给予染料木黄酮对阻断海马CA1区的DND无效。酪氨酸激酶抑制剂在缺血和再灌注损伤后选择性地阻断微管相关蛋白（MAP）-2激酶的磷酸化。这些结果表明，缺血性脑中的酪氨酸磷酸化对神经元损伤很重要，并且MAP-2激酶可能在迟发性神经元死亡的发生中起作用。
