Aberrant δPKC activation in the spinal cord of Wobbler mouse:: a model of motor neuron disease
Aberrant δPKC activation in the spinal cord of Wobbler mouse:: a model of motor neuron disease
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DOI：
10.1016/j.nbd.2004.08.017
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发表时间：
2005-02-01
影响因子：
6.1
通讯作者：
Pérez-Pinzón, MA
中科院分区：
文献类型：
--
作者：
Dave, KR;Raval, AP;Pérez-Pinzón, MA
蛋白激酶 C (PKC) 被认为在肌萎缩侧索硬化症 (ALS) 患者的病理学中发挥作用。 PKC delta (deltaPKC) 的激活可调节线粒体诱导的细胞凋亡。本研究的目的是确定 Wobbler 小鼠脊髓（运动神经元疾病模型）中是否发生 deltaPKC 激活。在 Wobbler 小鼠的脊髓中，可溶性部分中 deltaPKC 的水平显着降低，这与 deltaPKC 裂解的显着增加有关。由于已知 caspase-3 可以裂解 deltaPKC，因此我们通过免疫组织化学方法测定了 Wobbler 小鼠脊髓中的 caspase-3 激活情况。结果表明，Wobbler 小鼠脊髓的皮质脊髓束运动神经元中活化的 caspase-3 具有强烈的免疫反应性。根据这些结果，我们推测 caspase-3 激活会裂解 deltaPKC，从而促进 Wobbler 脊髓中的异常信号转导途径。 (C) 2004 Elsevier Inc. 保留所有权利。
Protein kinase C (PKC) was suggested to play a role in the pathology of amyotrophic lateral sclerosis (ALS) patients. Activation of PKC delta (deltaPKC) modulates mitochondrially induced apoptosis. The goal of the present study was to define whether deltaPKC activation occurs in Wobbler mouse spinal cord (a model of motor neuron disease). The level of deltaPKC in the soluble fraction was significantly decreased in the spinal cord of Wobbler mice, which was associated with a significant increase in deltaPKC cleavage. Since caspase-3 is known to cleave deltaPKC, we determined caspase-3 activation in the Wobbler mice spinal cord, immunohistochemically. The results demonstrated intense immunoreactivity for activated caspase-3 in corticospinal tract motor neurons of Wobbler mice spinal cord. We hypothesize from these results that caspase-3 activation cleaves deltaPKC, which in turn promotes an aberrant signal transduction pathway in the Wobbler spinal cord. (C) 2004 Elsevier Inc. All rights reserved.