Delayed neuronal death in ischemic hippocampus involves stimulation of protein tyrosine phosphorylation.
Delayed neuronal death in ischemic hippocampus involves stimulation of protein tyrosine phosphorylation.
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缺血海马中的延迟性神经元死亡涉及蛋白质酪氨酸磷酸化的刺激。
DOI：
10.1152/ajpcell.1996.271.4.c1085
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Takehiko Yanagihara
中科院分区：
文献类型：
--
作者：
T. Ohtsuki;M. Matsumoto;Kazuo Kitagawa;T. Mabuchi;Kenji Mandai;K. Matsushita;K. Kuwabara;M. Tagaya;S. Ogawa;H. Ueda;T. Kamada;Takehiko Yanagihara
谷氨酸在脑缺血再灌流后触发神经元退化。然而，传播细胞死亡的细胞内信号转导的细节仍不清楚。本研究调查了蛋白酪氨酸磷酸化是否介导了脑缺血后神经元的死亡。蒙古沙土鼠短暂性前脑缺血5~10min和SD大鼠谷氨酸类似物海人酸中毒(12 mg/kg)分别在2~4天和1天后选择性地引起海马神经元死亡。在此条件下，160 kDa、115 kDa、105 kDa、92 kDa和85 kDa蛋白在脑缺血后3~12h或海人酸致痫后4~8h，选择性地增加海马区酪氨酸残基的磷酸化水平。酪氨酸激酶，包括pp60c-src，被激活而不改变酪氨酸磷酸酶。给予酪氨酸激酶的选择性抑制剂--自由基酚，可减弱对酪氨酸磷酸化的刺激和脑缺血或注射海人藻酸后的海马区变性。结果提示，蛋白酪氨酸磷酸化可能通过谷氨酸超载促进脑缺血再灌流后成熟海马神经元的迟发性死亡。
Glutamate triggers neuronal degeneration after ischemia-reperfusion in the brain. However, the details of intracellular signal transduction that propagates cell death remain unknown. The present work investigated whether protein tyrosine phosphorylation mediates neuronal death in the ischemic brain. Transient forebrain ischemia for 5-10 min in Mongolian gerbils or intoxication with the glutamate analogue kainic acid (12 mg/kg) in Sprague-Dawley rats caused neuronal death selectively in the hippocampus 2-4 days or 1 day later, respectively. Under these conditions, 160-, 115-, 105-, 92-, and 85-kDa proteins showed a significant increase in tyrosyl residue phosphorylation selectively in the hippocampus 3-12 h after ischemia or 4-8 h after kainic acid-induced seizures. Tyrosine kinases, including pp60c-src, were activated without a change of tyrosine phosphatases. Administration of radicicol, a selective inhibitor of tyrosine kinases, attenuated stimulation of tyrosine phosphorylation and hippocampal degeneration after ischemia or kainic acid injection. The results suggest that protein tyrosine phosphorylation might propagate delayed neuronal death in the mature hippocampus through glutamate overload after ischemia-reperfusion.
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影响因子：
56.9
作者：
GRANT, SGN;ODELL, TJ;KANDEL, ER
通讯作者：
KANDEL, ER
影响因子：
56.9
作者：
FISCHER, EH;CHARBONNEAU, H;TONKS, NK
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TONKS, NK
影响因子：
56.9
作者：
BADING, H;GREENBERG, ME
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GREENBERG, ME
影响因子：
56.9
作者：
YAO, RJ;COOPER, GM
通讯作者：
COOPER, GM