Preventive effect of antioxidants in MPTP-induced mouse model of Parkinson's disease.
Oxidative stress to dopaminergic neurons is believed to be one of the causes of neurodegeneration in Parkinson's disease (PD). It was investigated whether N-acetylcysteine (NAC) and l-2-oxothiazolidine-4-carboxylate (OTC) have a preventive effect in an oxidative stress-induced model of PD. We found that NAC and OTC prevent degradation of PARP during auto-oxidized dopamine- or auto-oxidized L-DOPA-induced apoptosis in PC12 cells. In an animal model study, NAC and OTC showed a preventive effect against MPTP-induced loss of tyrosine hydroxylase-positive neurons, and suppressed the nuclear translocation of c-jun N-terminal kinase (JNK), suggesting that NAC and OTC can prevent MPTP-induced apoptosis by suppressing JNK activation. Therefore, these results suggest that NAC and OTC can be used as potential agents to prevent the progression of PD.
Park
Soon-Won
SW
Department of Biochemistry, College of Medicine, Pusan National University, Busan 602-739, South Korea.
Kim
Sun-Hee
SH
Park
Kyu-Hyun
KH
Kim
Sang-Doo
SD
Kim
Joo-Young
JY
Baek
Sun-Yong
SY
Chung
Byung-Seon
BS
Kang
Chi-Dug
CD
D000111:Acetylcysteine / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007150:Immunohistochemistry / Q000379:methods; D048031:JNK Mitogen-Activated Protein Kinases; D020267:MPTP Poisoning / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016716:PC12 Cells; D011761:Pyrrolidonecarboxylic Acid; D051381:Rats; D013844:Thiazoles / Q000627:therapeutic use*; D053778:Thiazolidines; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000975:Antioxidants; D015259:Dopamine Agents; D013844:Thiazoles; D053778:Thiazolidines; D014446:Tyrosine 3-Monooxygenase; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D011761:Pyrrolidonecarboxylic Acid; D004298:Dopamine; D000111:Acetylcysteine; C029536:2-oxothiazolidine-4-carboxylic acid