Statins potentiate caspase-3 activity in immortalized murine neurons
Statins potentiate caspase-3 activity in immortalized murine neurons
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DOI：
10.1016/j.neulet.2003.10.022
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发表时间：
2004-01-23
影响因子：
2.5
通讯作者：
Trapp, T
中科院分区：
文献类型：
--
作者：
Föcking, M;Besselmann, M;Trapp, T
他汀类药物是降脂药物，已被证明可以降低动脉粥样硬化性心血管疾病的发病率和死亡率。然而，越来越多的流行病学研究证据表明，长期使用他汀类药物治疗对肝外组织有不良影响，并增加了神经病变的风险。为了研究潜在的分子机制，我们分析了他汀类药物是否影响永生化神经元中caspase-3的活性。洛伐他汀和美伐他汀不能激活caspase-3，但当星形孢菌素启动凋亡信号转导时，它们强烈增强其活性。与他汀类药物和星形孢菌素共孵育后，caspase-3活性的增加被促凋亡GTdR RhoB蛋白水平的增加所抵消。我们的数据提供的证据表明，他汀类药物增强神经细胞凋亡，因此，当神经系统疾病患者用这些药物治疗时，给予仔细评估的理由。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
Statins are lipid-lowering drugs that have been shown to reduce atherosclerotic cardiovascular morbidity and mortality. However, there is growing evidence from epidemiological studies that long-term treatment with statins has unwanted effects on extrahepatic tissue and increases the risk for neuropathy. To investigate underlying molecular mechanisms we analyzed whether statins influence the activity of caspase-3 in immortalized neurons. Lovastatin and mevastatin are not able to activate caspase-3 but they strongly potentiate its activity when apoptotic signal transduction is initiated by staurosporine. The increase in caspase-3 activity after coincubation with statins and staurosporine was paralleled by an increase in the protein level of the pro-apoptotic GTPase RhoB. Our data provide evidence that statins enhance neuronal apoptosis and therefore give reasons for a careful evaluation when patients with neurological diseases are treated with these drugs. (C) 2003 Elsevier Ireland Ltd. All rights reserved.