首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Autophosphorylation as a possible mechanism of calcium/calmodulin-dependent protein kinase II inhibition during ischemia.
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Autophosphorylation as a possible mechanism of calcium/calmodulin-dependent protein kinase II inhibition during ischemia.

机译:自磷酸化是缺血期间钙/钙调蛋白依赖性蛋白激酶II抑制的可能机制。

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摘要

Cardiac arrest induced rat brain ischemia of 15 min duration produces a rapid and profound decrease in activity of calcium/calmodulin stimulated protein kinase (CaM-KII). In contrast to that, the total amount of enzyme protein remains stable as revealed by Western blotting (alpha subunit specific) analysis. Ischemic insult also results in translocation of the enzyme toward plasmatic membranes, reducing its content in soluble (cytosolic) fraction down to 7% with respect to 50% of control. The qualitatively similar translocation can be achieved by autophosphorylation of the control enzyme in vitro. Moreover, severely reduced response of immunoprecipitated enzyme to autophosphorylation observed after ischemia ex vivo probably reflects the higher level of its endogenous phosphorylation during the insult. The results strongly suggest that among various possible mechanisms of postischemic CaM-KII inhibition the most probable would be that involving abnormal or irreversible phosphorylation of the enzyme molecule. It would consequently block or inhibit the autophosphorylation/dephosphorylation cycle of endogenous CaM-KII interconversion necessary for its full catalytic activity.
机译:持续15分钟的心脏骤停诱发的大鼠脑缺血会导致钙/钙调蛋白刺激的蛋白激酶(CaM-KII)活性迅速而深刻地降低。与此相反,如蛋白质印迹法(α亚基特异性)分析所揭示的,酶蛋白的总量保持稳定。缺血性损伤还导致酶向质膜移位,相对于对照的50%,其在可溶性(胞质)级分中的含量降低至7%。通过在体外使对照酶自身磷酸化,可以实现定性相似的易位。而且,离体缺血后观察到的免疫沉淀酶对自身磷酸化的反应严重降低,可能反映了其在损伤期间内源性磷酸化水平较高。结果强烈表明,在缺血后CaM-KII抑制的各种可能机制中,最可能的是涉及酶分子异常或不可逆磷酸化的机制。因此,它将阻止或抑制其完全催化活性所必需的内源性CaM-KII相互转化的自磷酸化/去磷酸化循环。

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