Melatonin attenuates amyloid beta25-35-induced apoptosis in mouse microglial BV2 cells
Melatonin attenuates amyloid beta25-35-induced apoptosis in mouse microglial BV2 cells
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DOI：
10.1016/j.neulet.2005.01.003
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发表时间：
2005-05-20
影响因子：
2.5
通讯作者：
Kim, EH
中科院分区：
文献类型：
--
作者：
Jang, MH;Jung, SB;Kim, EH
褪黑激素具有很强的抗氧化作用，能够直接抑制多种活性氧（ROS）。本研究调查是否褪黑激素具有保护作用，对A β诱导的细胞毒性的小胶质细胞。用A β处理的细胞表现出凋亡的几个特征，而在暴露于A β之前用褪黑激素预处理的细胞显示出这种凋亡特征的发生减少。先前的几项研究已经证明活性氧参与了A β诱导的神经毒性，并且有报道称A β产生的活性氧导致核因子-κ B的活化（NF-κ B），转录因子;在本研究中用褪黑激素预处理降低了A β诱导的细胞内ROS产生的水平，抑制了NF-κ B活化，并抑制A β诱导的caspase-3酶活性的增加。此外，发现用褪黑激素预处理抑制A β诱导的bax mRNA水平的增加，并且其增强bcl-2表达水平。基于这些发现，作者推测褪黑激素可能通过减弱A β诱导的细胞凋亡而提供治疗阿尔茨海默病的有效手段。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Melatonin has been reported to possess strong antioxidant actions, and is able to directly scavenge a variety of reactive oxygen species (ROS). The present study investigated whether melatonin possesses protective effects against A beta-induced cytotoxicity in microglial cells. Cells treated with A beta exhibited several characteristic features of apoptosis, while cells pre-treated with melatonin prior to exposure to A beta showed a decrease in the occurrence of such apoptotic, features. Several previous studies have demonstrated the involvement of ROS in A beta-induced neurotoxicity, and ROS generated by A beta have been reported to lead to the activation of nuclear factor-kappa B (NF-kappa B), a transcription factor; pre-treatment with melatonin in the present study reduced the level of A beta-induced intracellular ROS generation, inhibited NF-kappa B activation, and suppressed the A beta-induced increase in caspase-3 enzyme activity. In addition, it was found that pre-treatment with melatonin inhibits A beta-induced increase in the levels of bax mRNA and that it enhances the level of bcl-2 expression. Based on these findings, the authors speculate that melatonin may provide an effective means of treatment for Alzheimer's disease through attenuation of A beta-induced apoptosis. (c) 2005 Elsevier Ireland Ltd. All rights reserved.