Kirschenbaum B, Pulsinelli W A
Cerebrovascular Disease Research Center, Cornell University Medical College, New York, NY 10021.
Brain Res. 1990 Mar 12;511(1):21-9. doi: 10.1016/0006-8993(90)90221-v.
Disruption of the brain's protein phosphorylation system by ischemia may cause irreversible metabolic and structural alterations leading eventually to cell death. To examine the effect of ischemia on the phosphorylation state of brain proteins, tissue homogenates derived from the hippocampus, striatum and neocortex of normal rats and rats subjected to severe forebrain ischemia were phosphorylated with [gamma-32P]ATP. The phosphorylated proteins were separated by two-dimensional polyacrylamide gel electrophoresis and changes were assessed by autoradiography. Cerebral ischemia caused marked alterations of the phosphorylation state of many brain proteins; phosphorylation of some proteins was increased while phosphorylation of others was decreased. Despite differences in the sensitivity of the hippocampus, striatum and neocortex to ischemic injury the direction and approximate magnitude of protein phosphorylation changes caused by ischemia were similar in all three regions. Since the pattern of protein phosphorylation in the ischemia-vulnerable hippocampus was identical to that in the ischemia-resistant paramedian neocortex we conclude that abnormalities of protein phosphorylation may be necessary for ischemic injury to neurons but none are sufficient to explain the selective vulnerability of certain brain regions to ischemic damage.
缺血对大脑蛋白质磷酸化系统的破坏可能会导致不可逆的代谢和结构改变，最终导致细胞死亡。为了研究缺血对脑蛋白磷酸化状态的影响，用[γ-32P]ATP对正常大鼠以及遭受严重前脑缺血的大鼠的海马体、纹状体和新皮质的组织匀浆进行磷酸化处理。通过二维聚丙烯酰胺凝胶电泳分离磷酸化蛋白，并通过放射自显影评估变化。脑缺血导致许多脑蛋白的磷酸化状态发生显著改变；一些蛋白的磷酸化增加，而另一些蛋白的磷酸化减少。尽管海马体、纹状体和新皮质对缺血损伤的敏感性存在差异，但缺血引起的蛋白磷酸化变化的方向和大致幅度在这三个区域是相似的。由于易缺血的海马体中的蛋白磷酸化模式与抗缺血的旁正中新皮质中的模式相同，我们得出结论，蛋白磷酸化异常可能是神经元缺血损伤所必需的，但没有一种异常足以解释某些脑区对缺血损伤的选择性易感性。
