Laboratory of Pharmacology, College of Pharmacy, Sungkyunkwan University, Chunchun-dong, Suwon, 440-746, Republic of Korea.
Neurol Sci. 2010 Jun;31(3):307-13. doi: 10.1007/s10072-010-0216-6. Epub 2010 Feb 3.
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.
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，胆绿素进而被还原为胆红素、CO 和游离铁。HO-1 可被多种有害刺激诱导，包括氧化应激，它在不同细胞中具有对抗细胞毒性的保护作用。1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPP(+)）是一种诱导多巴胺能神经元变性的神经毒性物质。本研究探讨了 MPP(+) 是否可以诱导 HO-1，以及 HO-1 是否可以对抗 MPP(+)诱导的 PC-12 细胞毒性。MPP(+) 可迅速诱导 HO-1 的表达。HO-1 抑制剂锌原卟啉-IX（ZnPP-IX）可显著增加 MPP(+)诱导的细胞毒性和活性氧（ROS）的产生。HO 的两种产物（胆绿素或胆红素）可完全阻断 ZnPP-IX 引起的 ROS 产生增加，而 ZnPP-IX 引起的细胞毒性增加则部分减弱。这表明 HO-1 表达可能对 MPP(+)诱导的细胞毒性具有一定的保护作用。
