Protective effects of heme oxygenase-1 against MPP+-induced cytotoxicity in PC-12 cells
Protective effects of heme oxygenase-1 against MPP+-induced cytotoxicity in PC-12 cells
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DOI：
10.1007/s10072-010-0216-6
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发表时间：
2010-06-01
影响因子：
3.3
通讯作者：
Lee, Seok-Yong
中科院分区：
文献类型：
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作者：
Bae, Jung-Woo;Kim, Mi-Jeong;Lee, Seok-Yong
血红素加氧酶-1 （HO-1）催化血红素降解为胆绿素的限速步骤，胆绿素又被还原为胆红素、一氧化碳和游离铁。HO-1可被包括氧化应激在内的多种有害刺激诱导，并对不同细胞的细胞毒性具有保护作用。1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPP+）是一种神经毒性物质，可诱导多巴胺能神经元变性。本研究考察了MPP+是否能诱导HO-1，以及HO-1是否对MPP+诱导的PC-12细胞毒性具有保护作用。MPP+触发HO-1的诱导相对较快。HO-1抑制剂锌原卟啉- ix （ZnPP-IX）显著增加了MPP+诱导的细胞毒性和活性氧（ROS）的产生。ZnPP-IX对ROS的增加作用被两种HO产物（胆红素或胆红素）完全抵消，而ZnPP-IX对细胞毒性的增加作用被部分减弱。提示HO-1表达可能对MPP+诱导的细胞毒性具有一定的细胞保护作用。
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.