Role of protein kinase C in thedevelopment of ischemic brain edema

蛋白激酶C在缺血性脑水肿发生中的作用

• 批准号: 04670868
• 负责人: MABE Hideo
• 金额: $ 1.28万
• 依托单位: Nagoya City University ( C )
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670868/
• 关键词: Cerebral Ischemia; Brain Edema; Protein Kinase C; Na^+; K^+-ATPase

To clarify the oile of protein kinase C (PKC) in the development of ischemic brain edema, we examined protein kinase C activity, Na^+/K^+-ATPase activity and brain water content in focal cerebral ischemia in the rat.Focal carebral ishemia was induced by the occlusion of the right middle cerebral artery (MCA occlusion).While PKC activity in the ischemic areas did mot sihnificantly change compared to preischemic levels at 2 hours after MCA occlusion, PKC activity in the ischemic areas significantly decreased in both cytosole and membrane fraction compared to preischemic levels at 4 hours after MCA occlusion(p<0.001).Na^+/K^+-ATPase activity in the ischemic cerebral hemispheres decreased in comparison to the non-ischemic cerebral hemisphere at 4 hours after MCA occlusion. PKC activator, phorbol 12-myristate 13-acetate (PMA), elicited an increase of the level of Na^+/K^+-ATPase activity in the ischemic cerebral hemisphere to the level present in the non-ischemic cerebral hemisphere. Four hours after MCA occlusion, brain water content in the ischemic cerebral himisphere significantly increased compared to the preischemic level. pretreatment with PMA prevented an increase in water content in the ischemic hemishere at 4 hours after MCA occlusion. On the other hand, pretreatment with PKC inhibitor, H-7 and ataurosporine, did not prevent an increase in brain water content in the ischemic hemispere at 4 hours after MCA occlusion.These results suggest that protein kinase C regulates Na^+/K^+-ATPasa activity and that decreased activity of PKC in cerebral ischemia induces the reduction if Na^+/K^+-ATPase activity, leading to the development of ischemic brain edema.

为了阐明蛋白激酶C（PKC）在缺血性脑水肿发生发展中的作用，我们检测了蛋白激酶C活性，大鼠局灶性脑缺血Na^+/K^+-ATP酶活性和脑含水量的变化虽然缺血区的PKC活性在MCA闭塞后2小时与缺血前水平相比没有显著变化，MCA闭塞后4小时，缺血区PKC活性在胞浆和膜组分中均显著低于缺血前水平（p<0.001）。与非缺血侧相比，缺血侧大脑半球的Na^+/K^+-ATP酶活性降低。MCA闭塞后4小时缺血大脑半球。PKC激活剂佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）可使缺血大脑半球的Na^+/K^+-ATP酶活性水平升高至非缺血大脑半球的水平。MCA阻断后4 h，缺血侧大脑半球脑含水量较缺血前显著增加。PMA预处理可防止MCA闭塞后4小时缺血半脑含水量的增加。另一方面，PKC抑制剂H-7和ataurosporine预处理不能阻止MCA阻断后4小时缺血半球脑含水量的增加，这些结果表明，蛋白激酶C调节Na^+/K^+-ATP酶活性，脑缺血时PKC活性降低导致Na^+/K ^+-ATP酶活性降低，导致缺血性脑水肿的发展。