High level calcineurin activity predisposes neuronal cells to apoptosis
High level calcineurin activity predisposes neuronal cells to apoptosis
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DOI：
10.1074/jbc.274.48.34450
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发表时间：
1999-11-26
影响因子：
4.8
通讯作者：
Kirino, T
中科院分区：
文献类型：
--
作者：
Asai, A;Qiu, JH;Kirino, T
钙调磷酸酶是一种钙/钙调蛋白依赖性蛋白磷酸酶，在大脑的几个特定区域大量表达，这些区域特别容易受到中风，癫痫和神经退行性疾病的影响。在这项研究中，我们评估了高水平的钙调神经磷酸酶活性对神经细胞的影响。病毒介导的钙调磷酸酶的高水平组成性活性使神经元细胞容易受到血清减少或短暂暴露于钙离子载体诱导的细胞凋亡的影响。腺病毒介导的，高水平的钙调磷酸酶强制活性诱导细胞色素c/半胱天冬酶3依赖的神经元凋亡。与钙调磷酸酶抑制剂环孢素A和FK 506预孵育降低了对凋亡的敏感性。高水平的Bcl-2或CrmA的组成性表达或与特定的caspase-3抑制剂孵育抑制钙调神经磷酸酶诱导的凋亡。这些数据表明，即使在亚致死条件下，高水平的钙调神经磷酸酶的组成性活性使神经元细胞易于发生细胞色素c/半胱天冬酶-3依赖性凋亡。
Calcineurin is a Ca2+/calmodulin-dependent protein phosphatase that is abundantly expressed in several specific areas of the brain, which are exceptionally vulnerable to stroke, epilepsy, and neurodegenerative diseases. In this study, we assessed the effects of high level activity of calcineurin on neuronal cells. Virus-mediated high level constitutive activity of calcineurin rendered neuronal cells susceptible to apoptosis induced by serum reduction or by a brief exposure to calcium ionophore. Adenovirus-mediated, high level forced activity of calcineurin induced cytochrome c/caspase-3-dependent apoptosis in neurons. Preincubation with the calcineurin inhibitors cyclosporin A and FK506 reduced susceptibility to apoptosis. High level constitutive expression of Bcl-2 or CrmA or incubation with a specific caspase-3 inhibitor inhibited the calcineurin-induced apoptosis. These data indicate that high level constitutive activity of calcineurin predisposes neuronal cells to cytochrome c/caspase-3 dependent apoptosis even under sublethal conditions.