Protective effect of melatonin on β-amyloid-induced apoptosis in rat astroglioma C6 cells and its mechanism
Protective effect of melatonin on β-amyloid-induced apoptosis in rat astroglioma C6 cells and its mechanism
复制标题
DOI：
10.1016/j.freeradbiomed.2004.08.023
复制
发表时间：
2004-12-01
影响因子：
7.4
通讯作者：
Zhang, JT
中科院分区：
文献类型：
--
作者：
Feng, Z;Zhang, JT
星形细胞增多是淀粉样斑块的共同特征。A-星形胶质细胞相互作用对神经元产生有害影响，这可能有助于阿尔茨海默病（AD）的神经退行性变。星形胶质细胞凋亡的调控在中枢神经系统的生理和病理过程中是必不可少的。褪黑激素是一种有效的抗氧化剂和自由基清除剂。以前，我们表明褪黑激素减轻了AD的APP 695转基因小鼠模型的学习和记忆缺陷。在这项研究中，褪黑激素的重要性，在A β诱导的星形胶质细胞样细胞凋亡的管理进行了讨论。我们发现用Abeta 25 -35或Abeta 1 -42处理的大鼠星形胶质瘤C6细胞发生凋亡，并且在10（-5）、10（-6）和10（-7）M的褪黑素预处理显著减弱Abeta 25 -35或Abeta 1 -42诱导的凋亡。褪黑激素的抗凋亡作用是非常可重复的，并证实了多种定量方法，包括MTT细胞活力测定，Hoechst 33342核染色，DNA片段化分析，流式细胞仪分析。此外，褪黑激素有效地抑制了A β 1 -42诱导的一氧化氮形成，显著地防止了A β 1 -40诱导的细胞内钙超载，并显著地减轻了A β 1 -40诱导的膜刚性。我们的研究结果表明，除了提供直接的抗氧化剂保护神经元的有益效果，褪黑激素可以通过促进神经胶质细胞的存活来增强对Abeta诱导的神经毒性的神经保护。(C)2004爱思唯尔公司All rights reserved.
Astrocytosis is a common feature of amyloid plaques. The A-astrocyte interaction produces a detrimental effect on neurons, which may contribute to neurodegeneration in Alzheimer disease (AD). The regulation of astrocyte apoptosis is essential to physiological and pathological processes in the CNS. Melatonin is a potent antioxidant and free radical scavenger. Previously, we showed that melatonin alleviated the learning and memory deficits in the APP 695 transgenic mouse model of AD. In this study, the importance of melatonin in the management of Abeta-induced apoptosis in an astrocyte-like cell is discussed. We found that rat astroglioma C6 cells treated with Abeta25-35 or Abeta1-42 undergo apoptosis and that melatonin pretreatment at 10(-5), 10(-6), and 10(-7) M significantly attenuates Abeta25-35- or Abeta1-42-induced apoptosis. The antiapoptotic effects of melatonin were extremely reproducible and corroborated by multiple quantitative methods, including an MTT cell viability assay, Hoechst 33342 nuclei staining, DNA fragmentation analysis, and flow cytometric analysis. In addition, melatonin effectively suppressed Abeta1-42-induced nitric oxide formation, remarkably prevented Abeta1-40-induced intracellular calcium overload, and significantly alleviated Abeta1-40-induced membrane rigidity. Our results demonstrate that, in addition to the beneficial effects of providing direct antioxidant protection to neurons, melatonin may enhance neuroprotection against Abeta-induced neurotoxicity by promoting the survival of glial cells. (C) 2004 Elsevier Inc. All rights reserved.