Ishido Masami
Environmental Risk Research Programme, National Institute for Environmental Studies, Tsukuba, Japan.
J Pineal Res. 2007 Mar;42(2):125-30. doi: 10.1111/j.1600-079X.2006.00390.x.
Melatonin, a secretory product of the pineal gland, is involved in the regulation of circadian and seasonal rhythms, in oncostasis, and in inducing osteoblast differentiation. Furthermore, melatonin is a scavenger of a number of reactive oxygen and reactive nitrogen species both in vitro and in vivo. In this study, the antioxidant nature of melatonin was shown to prevent cultured neural cells from apoptosis induced by endocrine-disrupting chemical, maneb. The neurotoxicity of the fungicide, maneb (1 microg/mL), on the PC12 cells was elicited through apoptotic cell death, concomitant with aggregation of alpha-synuclein, a feature of Parkinson's disease. Activation of caspase-3/7 was associated with this process. A fluorescence rationing technique using a mitochondrial dye revealed that maneb altered the mitochondrial membrane potential of the neural cells. However, melatonin (1 nm) largely prevented the neural cells from the neural toxicant by inhibition of both caspase-3/7 activation and disruption of the mitochondrial transmembrane potential. Furthermore, aggregation of alpha-synuclein by maneb was also inhibited by melatonin. Thus, melatonin prevents maneb-induced neurodegeneration at a nighttime physiological blood concentration, most likely by inhibiting the aggregation of alpha-synuclein as well as preventing mitochondrial dysfunction in PC 12 cells.
褪黑素是松果体分泌的一种产物，参与昼夜节律和季节节律的调节、肿瘤抑制以及诱导成骨细胞分化。此外，褪黑素在体外和体内都是多种活性氧和活性氮物质的清除剂。在本研究中，褪黑素的抗氧化特性被证明可防止培养的神经细胞因内分泌干扰化学物质代森锰锌诱导的凋亡。杀菌剂代森锰锌（1微克/毫升）对PC12细胞的神经毒性是通过凋亡性细胞死亡引发的，同时伴有帕金森病的一个特征——α-突触核蛋白的聚集。半胱天冬酶-3/7的激活与这一过程相关。使用线粒体染料的荧光定量技术显示，代森锰锌改变了神经细胞的线粒体膜电位。然而，褪黑素（1纳摩尔）通过抑制半胱天冬酶-3/7的激活和线粒体跨膜电位的破坏，在很大程度上保护神经细胞免受神经毒物的侵害。此外，褪黑素还抑制了代森锰锌诱导的α-突触核蛋白聚集。因此，褪黑素在夜间生理血液浓度下可预防代森锰锌诱导的神经退行性变，很可能是通过抑制α-突触核蛋白的聚集以及防止PC12细胞中的线粒体功能障碍来实现的。
