Campos-González R, Kindy M S
Department of Surgery, University of Kentucky Medical Center, Lexington 40536-0084.
J Neurochem. 1992 Nov;59(5):1955-8. doi: 10.1111/j.1471-4159.1992.tb11032.x.
The tyrosine phosphorylation of microtubule-associated protein (MAP) kinase was examined in the gerbil brain after transient ischemia and reperfusion. Phosphorylation of MAP kinase was maximal within 1 min of reperfusion following 5 min of ischemia and returned to control levels as early as 5 min postischemia. The greatest increase in MAP kinase phosphorylation was detected in the hippocampus, with minor increases in other ischemic regions of the brain. Several tyrosine-phosphorylated proteins were detected in the gerbil hippocampus; however, the ischemia and reperfusion injury only increased tyrosine phosphorylation of MAP kinase. The increase in tyrosine phosphorylation was prevented by the N-methyl-D-aspartate (NMDA) receptor blocker (+)-MK-801, whereas a non-NMDA receptor blocker, 6-cyano-7-nitroquinoxaline-2,3-dione, was ineffective. Pretreatment of gerbils with calcium channel blockers also prevented the tyrosine phosphorylation of MAP kinase in the ischemic brain. Altogether, these results imply an involvement of glutamate receptors and calcium during the tyrosine phosphorylation of MAP kinase. Tyrosine phosphorylation was also prevented when ischemia and reperfusion were conducted under hypothermic conditions, which protect against neurodegenerative damage. These findings implicate a role for MAP kinase in neuronal damage resulting from ischemia and reperfusion.
在沙土鼠短暂性脑缺血再灌注后，检测了微管相关蛋白（MAP）激酶的酪氨酸磷酸化情况。在缺血5分钟后的再灌注1分钟内，MAP激酶的磷酸化达到最大值，并在缺血后5分钟时就早早恢复到对照水平。在海马体中检测到MAP激酶磷酸化的最大增加，而在大脑的其他缺血区域只有轻微增加。在沙土鼠海马体中检测到几种酪氨酸磷酸化蛋白；然而，缺血再灌注损伤仅增加了MAP激酶的酪氨酸磷酸化。N-甲基-D-天冬氨酸（NMDA）受体阻滞剂（+）-MK-801可阻止酪氨酸磷酸化增加，而非NMDA受体阻滞剂6-氰基-7-硝基喹喔啉-2,3-二酮则无效。用钙通道阻滞剂预处理沙土鼠也可防止缺血脑中MAP激酶的酪氨酸磷酸化。总之，这些结果表明谷氨酸受体和钙参与了MAP激酶的酪氨酸磷酸化过程。当在低温条件下进行缺血再灌注时，酪氨酸磷酸化也受到阻止，低温可防止神经退行性损伤。这些发现表明MAP激酶在缺血再灌注导致的神经元损伤中起作用。
