Ischemia‐Induced Translocation of Ca2+/Calmodulin‐Dependent Protein Kinase II: Potential Role in Neuronal Damage
Ischemia‐Induced Translocation of Ca2+/Calmodulin‐Dependent Protein Kinase II: Potential Role in Neuronal Damage
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缺血诱导的 Ca2+/钙调蛋白依赖性蛋白激酶 II 易位：在神经元损伤中的潜在作用
作者：
J. Aronowski;J. Grotta;M. Waxham
摘要：在大鼠全脑缺血后测定了Ca 2 +/钙调蛋白（CaM）依赖性、Ca 2 +/磷脂依赖性和环AMP依赖性蛋白激酶（分别为CaM-KII、PKC和PKA）的活性。在缺血动物的海马和大脑皮层区域，CaM-KII和PKC活性均显著降低，而PKA活性未检测到变化。CaM-KII活性的丧失比PKC活性的丧失更显著、更持久，并与缺血持续时间相关。在粗匀浆的上清液和沉淀组分中均发现酶活性的这些降低。当分析上清液和沉淀物中CaM-KII 50-kDa蛋白的量时，在上清液组分中检测到显著减少，这导致沉淀物中CaM-KII的量增加。因此，上清液中CaM-KII活性的丧失可以通过酶转移到沉淀物来解释。CaM-KII的失活是否发生在酶从上清液转移到沉淀物的过程中或之后尚不清楚。我们的研究结果表明，CaM-KII活性的丧失与缺血相关的神经元损伤平行; CaM-KII活性的下调与酶向颗粒部分的易位相一致，并且提出这实际上可能是控制过度CaM-KII磷酸化的机制。
Abstract: The activities of Ca2+/calmodulin (CaM)‐dependent, Ca2+/phospholipid‐dependent, and cyclic AMP‐dependent protein kinases (CaM‐KII, PKC, and PKA, respectively) were determined in rat brains after global ischemia. Both CaM‐KII and PKC activities were significantly depressed in both hippocampal and cerebral cortical regions of ischemic animals, whereas no change was detected in PKA activity. The loss of CaM‐KII activity was more dramatic and more sustained than the loss of PKC activity and correlated with the duration of ischemia. These decreases in enzyme activity were found in both supernatant and pellet fractions from crude homogenates. When the supernatant and pellet were analyzed for the amount of CaM‐KII 50‐kDa protein, a significant decrease was detected in supernatant fractions that paralleled a gain in the amount of CaM‐KII in the pellet. Thus, the loss of CaM‐KII activity in the supernatant can be explained by translocation of the enzyme to the pellet. Whether inactivation of CaM‐KII occurs during or after the enzyme translocates from the supernatant to the pellet is unknown. Our results indicate that loss in CaM‐KII activity parallels neuronal damage associated with ischemia; down‐regulation of CaM‐KII activity coincided with translocation of the enzyme to the particulate fraction, and it is proposed that this may be, in fact, a mechanism for controlling excessive CaM‐KII phosphorylation.
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Ca2/钙调蛋白激酶被磷脂酰肌醇信号通路激活，并在 PC12 细胞中变得不依赖于 Ca2( )。
DOI：
--
发表时间：
1990
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
MacNicol,M;Jefferson,AB;Schulman,H
通讯作者：
Schulman,H
影响因子：
8.3
作者：
J. C. Grotta;C. Picone;R. Earls;Randy Strong;L. Yao;J. R. Dedman
通讯作者：
J. C. Grotta;C. Picone;R. Earls;Randy Strong;L. Yao;J. R. Dedman
影响因子：
7.7
作者：
Mishra S;Verhalen B;Stein RA;Wen PC;Tajkhorshid E;Mchaourab HS
通讯作者：
Mchaourab HS
DOI：
10.1073/pnas.81.3.945
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
KELLY, PT;MCGUINNESS, TL;GREENGARD, P
通讯作者：
GREENGARD, P
Ca2/CaM 依赖性多功能蛋白激酶的底物特异性：来自脑、肝脏和骨骼肌的同工酶的比较。
DOI：
10.1016/s0006-291x(88)80508-4
发表时间：
1988
影响因子：
3.1
作者：
Shenolikar,S;Langston,J;Schworer,CM;Kelly,PT
通讯作者：
Kelly,PT