Protective effects of a new metalloporphyrin on paraquat-induced oxidative stress and apoptosis in N27 cells.
Paraquat (PQ, 1,1'-dimethyl-4,4'-bipyridinium), a widely-used herbicide, has been suggested as a potential etiologic factor for the development of Parkinson's disease. In recent years, many studies have focused on the mechanism(s) of PQ neurotoxicity. In this study, we examined the neuroprotective effect of manganese (III) meso-tetrakis (N,N'-diethylimidazolium) porphyrin (MnTDM), a superoxide dismutase/catalase mimetic, on PQ-induced oxidative stress and apoptosis in 1RB3AN27 (N27) cells, a dopaminergic neuronal cell line. The results indicated that MnTDM significantly attenuated PQ-induced loss of cell viability, glutathione depletion, and reactive oxygen species production. MnTDM also ameliorated PQ-induced morphological nuclear changes of apoptosis and increased rates of apoptosis. In addition, our data provide direct evidence that MnTDM suppressed PQ-induced caspase-3 cleavage, possibly a key event of PQ neurotoxicity. These observations suggested that oxidative stress and apoptosis are implicated in PQ-induced neurotoxicity and this toxicity could be prevented by MnTDM. These findings also proposed a novel therapeutic approach for Parkinson's disease and other disorders associated with oxidative stress.
Chen
Ping
P
School of Life Science and Technology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200092, China.
Li
Ang
A
Zhang
Mengjie
M
He
Meilan
M
Chen
Zhen
Z
Wu
Xiaokang
X
Zhao
Chunjun
C
Wang
Shilong
S
Liang
Liping
L
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008665:Metalloporphyrins / Q000494:pharmacology*; D008954:Models, Biological; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
C472668:AEOL 10150; D016166:Free Radical Scavengers; D008665:Metalloporphyrins; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione; D010269:Paraquat