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首页> 外文学位 >Transient forebrain ischemia in the rat triggers changes in protein phosphorylation and pyruvate dehydrogenase activity in vulnerable and resistant brain regions.
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Transient forebrain ischemia in the rat triggers changes in protein phosphorylation and pyruvate dehydrogenase activity in vulnerable and resistant brain regions.

机译：大鼠的短暂性前脑缺血会触发易感性和耐药性脑区域蛋白质磷酸化和丙酮酸脱氢酶活性的变化。

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摘要

Transient forebrain ischemia leads to the rapid demise of dorsal-lateral striatal neurons, the delayed death of hippocampal CA1 pyramidal neurons and the temporary dysfunction but full recovery of paramedian neocortical neurons. To investigate whether changes in protein phosphorylation can explain the unique vulnerability of some neurons and/or the delayed death of these cells, tissue homogenates derived from hippocampus, striatum and neocortex of normal rats, rats subjected to 30 minutes of severe forebrain ischemia and rats following 6 hours of cerebral reperfusion were phosphorylated with ({dollar}gamma{dollar}-{dollar}sp{lcub}32{rcub}{dollar}P) ATP. To test whether the depressed glucose utilization noted during reperfusion is caused by abnormal pyruvate dehydrogenase complex activity (PDHC) I measured the rate of decarboxylation of 1-{dollar}sp{lcub}14{rcub}{dollar}C pyruvate in brain homogenates derived from CA1 hippocampus and paramedian neocortex before, during and 2.5 hours following a 15 minute ischemic insult.; Cerebral ischemia markedly changed the phosphorylation state of many brain proteins, some increased, such as that of PDHC, while that of most proteins decreased. The general inhibition of protein phosphorylation seen during ischemia was further accentuated at 6 hours of reperfusion. Proteins with increased phosphorylation during ischemia returned during reperfusion to a phosphorylation state near control levels. Protein phosphorylation changes were similar in all 3 brain regions.; PDHC activity which increased approximately 300% during ischemia decreased approximately 30% from preischemic levels following 2.5 hours of reperfusion. A second ischemic insult or addition of Ca{dollar}sp{lcub}2+{rcub}{dollar} in vitro fully activated PDHC.; In conclusion: (1) ischemia-induced changes in brain protein phosphorylation cannot alone explain the selective vulnerability of neurons. However, persistant postischemic changes of the protein phosphorylation state may play some role in the development of delayed neuronal death, (2) PDHC activity, although depressed during recirculation, is capable of being fully activated and showed no regional difference that could be causally related to selective neuronal vulnerability. Mechanisms other than damage to PDHC or damage to its Ca{dollar}sp{lcub}2+{rcub}{dollar}-regulatory mechanisms are most likely responsible for the depressed PDHC activity and may play some role in the decreased utilization of glucose and the delayed death of neurons.
机译：短暂性前脑缺血导致背侧纹状体神经元快速死亡，海马CA1锥体神经元死亡延迟和暂时性功能障碍，但正中皮层新皮层神经元已完全恢复。为了研究蛋白质磷酸化的变化是否可以解释某些神经元的独特脆弱性和/或这些细胞的延迟死亡，正常大鼠海马，纹状体和新皮层的组织匀浆，遭受严重前脑缺血30分钟的大鼠以及用（{dollar}γ{dollar}-{dollar} sp {lcub} 32 {rcub} {dollar} P）ATP将6小时的脑再灌注磷酸化。为了测试在再灌注期间记录的葡萄糖利用率降低是否是由异常的丙酮酸脱氢酶复合活性（PDHC）引起的，我测量了衍生于脑的匀浆中1- {dol} sp {lcub} 14 {rcub} {dollar} C丙酮酸的脱羧速率在15分钟缺血性损伤之前，期间和2.5小时后从CA1海马和中新皮层中提取;脑缺血明显改变了许多脑蛋白的磷酸化状态，其中一些增加了，例如PDHC，而大多数蛋白则减少了。在再灌注6小时时，进一步增强了对缺血过程中蛋白质磷酸化的一般抑制作用。在缺血过程中磷酸化增加的蛋白质在再灌注过程中返回到控制水平附近的磷酸化状态。在所有三个大脑区域中，蛋白质的磷酸化变化都相似。在再灌注2.5小时后，缺血期间PDHC活性增加了约300％，较缺血前水平降低了约30％。在体外完全活化的PDHC中第二次缺血性损伤或添加Ca {dol} sp {lcub} 2+ {rcub} {dol}。结论：（1）缺血引起的脑蛋白磷酸化变化不能单独解释神经元的选择性脆弱性。然而，持续的缺血性蛋白磷酸化状态变化可能在延迟神经元死亡的发展中发挥一定作用。（2）PDHC活性尽管在再循环过程中被抑制，但能够被完全激活，并且没有显示出可能与选择性神经元脆弱性。除了破坏PDHC或破坏其Ca {dollar} sp {lcub} 2+ {rcub} {dollar}调节机制外，其他机制也很可能是PDHC活性降低的原因，并且可能在葡萄糖利用减少和神经元的延迟死亡。

著录项

  • 作者

    Kirschenbaum, Barry.;

  • 作者单位

    New York University.;

  • 授予单位 New York University.;
  • 学科 Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 1992
  • 页码 189 p.
  • 总页数 189
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经科学;
  • 关键词

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