Protective effects of heme oxygenase-1 against MPP+-induced cytotoxicity in PC-12 cells

被引:23
作者
Bae, Jung-Woo [1 ]
Kim, Mi-Jeong [1 ]
Jang, Choon-Gon [1 ]
Lee, Seok-Yong [1 ]
机构
[1] Sungkyunkwan Univ, Pharmacol Lab, Coll Pharm, Suwon 440746, South Korea
关键词
Heme oxygenase-1 (HO-1); Cytotoxicity; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridinium (MPP+); PC-12; cell; TRAUMATIC BRAIN-INJURY; OXIDATIVE STRESS; NITRIC-OXIDE; INTRACEREBRAL HEMORRHAGE; CARBON-MONOXIDE; BILIRUBIN; NEURONS; HO-1; 1-METHYL-4-PHENYLPYRIDINIUM; OVEREXPRESSION;
D O I
10.1007/s10072-010-0216-6
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Heme oxygenase-1 (HO-1) catalyses the rate-limiting step of heme degradation to biliverdin, which is in turn reduced to bilirubin, CO and free iron. HO-1 can be induced by several harmful stimuli including oxidative stress, and it has a protective role against the cytotoxicity in different cells. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridinium (MPP+) is a neurotoxic substance that induces the degeneration of dopaminergic neurons. This study examined whether HO-1 can be induced by MPP+ and whether HO-1 has a protective role against the MPP+-induced cytotoxicity in PC-12 cells. MPP+ triggered a relatively rapid induction of HO-1. The MPP+-induced cytotoxicity and reactive oxygen species (ROS) production markedly increased by HO-1 inhibitor, zinc protoporphyrin-IX (ZnPP-IX). The increase of ROS production by ZnPP-IX was completely abrogated by either two products of HO (biliverdin or bilirubin) while the increase of cytotoxicity by ZnPP-IX was attenuated partially. These suggest that HO-1 expression might have some cytoprotective effect against MPP+-induced cytotoxicity.
引用
收藏
页码:307 / 313
页数:7
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