PYRUVATE-DEHYDROGENASE ACTIVITY IN THE RAT CEREBRAL-CORTEX FOLLOWING CEREBRAL-ISCHEMIA
PYRUVATE-DEHYDROGENASE ACTIVITY IN THE RAT CEREBRAL-CORTEX FOLLOWING CEREBRAL-ISCHEMIA
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DOI：
10.1038/jcbfm.1989.53
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发表时间：
1989-06-01
影响因子：
6.3
通讯作者：
WIELOCH, T
中科院分区：
文献类型：
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作者：
CARDELL, M;KOIDE, T;WIELOCH, T
在双侧颈总动脉闭塞缺血 15 分钟后以及缺血 15 分钟后再循环 15 分钟、60 分钟和 6 小时后，研究脑缺血对大鼠大脑皮层匀浆中丙酮酸脱氢酶 (PDH) 酶复合物 (PDHC) 活性的影响。在同一动物的冷冻皮质组织中，测定了不稳定磷酸盐化合物、葡萄糖、糖原、乳酸和丙酮酸的水平。在对照动物的皮质中，[1-14C]丙酮酸脱羧率为9.6±。 nmol CO2（min-mg 蛋白质）或总 PDHC 活性的 40%。缺血 15 分钟结束时，这一比例增加至 89%。缺血 15 分钟后再循环 15 分钟时，PDHC 活性降至对照水平的 50%，并且在缺血后长达 6 小时内被抑制。这种活性的降低并不是由于总 PDHC 活性的降低。除了 ATP 水平降低外，能量代谢物水平的急剧变化在恢复 6 小时后基本恢复正常。二氯乙酸 (DCA) 是一种 PDH 激酶抑制剂，以 250 mg/kg 腹腔注射给予大鼠。 2 小时内四次，血糖水平显着降低至 7.4 .+-。 0.6 至 5.1 至 0.3 mmol/L 且完全活化的 PDHC。在动物中，血浆葡萄糖水平维持在8.3±的对照水平。通过静脉输注0.5μmol/g葡萄糖，PDHC的活性部分增加至95.+-。 4%。相反，缺血后 15 分钟时降低的 PDHC 活性不受 DCA 治疗的影响。在 DCA + 葡萄糖治疗的对照组和恢复组中，丙酮酸水平均下降了 50%。乳酸水平没有观察到显着差异。我们得出的结论是，缺血后 PDHC 活性的降低既不是由于酶蛋白的损失，也不是由于 PDH 激酶活性的增加，而可能是由于 PDH 磷酸酶活性的降低。这可能继发于 PDG 磷酸酶调节剂细胞水平的变化，最有可能是线粒体内钙浓度的降低。缺血后PDH活性降低可能与缺血后代谢抑制有关。
The effect of cerebral ischemia on the activity of pyruvate dehydrogenase (PDH) enzyme complex (PDHC) was investigated in homogenates fo froxen ratcerebral cortex followign 15 min of bilateral common carotid occulusion ischemia and following 15 min, 60 min, and 6 h of recirculation after 15 min of ischemia. In frozen cortical tissue from the same animals, the levels of labile phosphate compounds, glucose, glycogen, lactate, and pyruvate were determined. In cortex from control animals, the rate of [1-14C]pyruvate decarboxylation was 9.6 .+-. nmol CO2(min-mg protein) or 40% of the total PDHC activity. This fraction increased to 89% at the end of 15 min of ischemia. At 15 min of recirculation following 15 min of ischemia, the PDHC activity decreased to 50% of control levels and was drpressed for up to 6 h post ischemia. This decrease in activity was not due to a decrease in total PDHC activity. Apart from a reduction in ATP levels, the acute changes in the levels of energy metabolites were essentially normalized at 6 H of recovery. Dichloracetate (DCA), an inhibitor of PDH kinase, given to rats at 250 mg/kg i.p. four times over 2 h, significantly decreased blood glucose levels form 7.4 .+-. 0.6 to 5.1 to 0.3 mmol/L and fully activated PDHC. In animals in which the plasma glucose level was maintained at control levels of 8.3 .+-. 0.5 .mu.mol/g by intravenous infusion of glucose, the active portion of PDHC increased to 95 .+-. 4%. In contrast, the depressed PDHC activity at 15 min followign ischemia was not affected by the DCA treatment. In both DCA + glucose-treated control and recovery groups, the pyruvate levels decreased by 50%. No significant difference in the lactate levels was seen. We conclude that the depressed postischemic PDHC activity is not due to loss of enzyme protein nor to an increased PDH kinase activity, but is probably due to a decrase activity of PDH phosphatase. This could in turn be secondary to a change in the cellular levels of PDG phosphatase regulators, most probably a decreased intramitochondrial concentration of calcim. The postischemic decreases in PDH activity may be related to the postichemic metabolic depression.