Effects of melanin and manganese on DNA damage and repair in PC 12-derived neurons
Effects of melanin and manganese on DNA damage and repair in PC 12-derived neurons
复制标题
DOI：
10.1016/j.freeradbiomed.2004.01.019
复制
发表时间：
2004-05-01
影响因子：
7.4
通讯作者：
Sánchez-Ramos, JR
中科院分区：
文献类型：
--
作者：
Sava, V;Mosquera, D;Sánchez-Ramos, JR
在PC12来源的神经细胞培养中，研究了黑色素与锰相互作用产生神经毒性的机制。细胞与黑色素(25-500µg/ml)、氯化锰(10 ng/ml-100µg/ml)以及两者的组合孵育24小时和72小时，单独使用任何一种毒物对细胞活力的影响最小。黑色素和锰的组合以剂量依赖的方式导致PC12细胞的活力显著下降(高达60%)。8-羟基-2‘-脱氧鸟苷(8-oxodG)水平表明，DNA氧化损伤增加与细胞存活率下降有关。单独的黑色素，而不是单独的锰，会导致DNA氧化损伤增加。暴露24小时后，黑色素引起的8-oxodG的最大增幅约为对照组的7倍。单独及联合作用24 h后，细胞DNA修复酶8-氧鸟嘌呤DNA糖基酶(OGG1)活性升高，第3天OGG1活性降至对照水平以下，细胞存活率显著下降。观察到黑色素对OGG1活性有抑制作用。研究黑色素和锰对OGG1活性的调节可能会为帕金森氏病黑质神经元对氧化应激的脆弱性提供见解。(C)2004 Elsevier Inc.保留所有权利。
The mechanism of neurotoxicity produced by the interaction of melanin with manganese was investigated in PC12-derived neuronal cell cultures. The cells were incubated with melanin (25-500 mug/ml), MnCl2 (10 ng/ml-100 mug/ ml), and a combination of both substances for 24 and 72 h. Incubation with either toxicant alone resulted in a minimal decrease in cell viability. The combination of melanin and manganese caused significant (up to 60%) decreases in viability of PC12 cells in a dose-dependent manner. Increases in oxidative DNA damage, indicated by levels of 8-hydroxy-2'deoxyguanosine (8-oxodG), was associated with decreased cell viability. Melanin alone, but not manganese alone, resulted in increased oxidative DNA damage. The maximal increase in 8-oxodG caused by melanin was about seven times higher than control after 24 h of exposure. The activity of the DNA repair enzyme, 8-oxoguanine DNA glycosylase (OGG1), was increased in cells incubated with single toxicants and their combinations for 24 h. On the third day of incubation with the toxicants, activity of OGG1 declined below control levels and cell viability significantly decreased. Melanin was observed to have an inhibitory effect on OGG1 activity. Study of the regulation of OGG1 activity in response to melanin and manganese may provide insights into the vulnerability of nigral neurons to oxidative stress in Parkinson's disease. (C) 2004 Elsevier Inc. All rights reserved.