Protective effects of heme oxygenase-1 against MPP(+)-induced cytotoxicity in PC-12 cells.
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.
Bae
Jung-Woo
JW
Laboratory of Pharmacology, College of Pharmacy, Sungkyunkwan University, Chunchun-dong, Suwon, 440-746, Republic of Korea.
Kim
Mi-Jeong
MJ
Jang
Choon-Gon
CG
Lee
Seok-Yong
SY
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D001663:Bilirubin / Q000378:metabolism; D001664:Biliverdine / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020267:MPTP Poisoning / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000008:administration & dosage; D016716:PC12 Cells; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
D004791:Enzyme Inhibitors; D009498:Neurotoxins; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; C017803:zinc protoporphyrin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D001664:Biliverdine; D001663:Bilirubin