Neuroprotective effect of asymmetric dimethylarginine against 1-methyl-4-phenylpyridinium ion-induced damage in PC12 cells.
1. Asymmetric dimethylarginine (ADMA) is a well-known endogenous nitric oxide synthase (NOS) inhibitor. Although it has been shown to be a novel risk marker in cardiovascular medicine and chronic kidney disease, we speculated that in some states associated with excess of nitric oxide (NO), such as 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neuronal injury, ADMA might be protective by limiting the toxic effect of high concentrations of NO. 2. The aim of the present study is to explore the protection of ADMA against MPP(+)-induced apoptosis and the molecular mechanisms underlying in PC12 cells. 3. We found that exogenous application of ADMA obviously protected PC12 cells against MPP(+)-induced cytotoxicity and apoptosis not only by reducing the loss of mitochondrial membrane potential, but also by attenuating an increase in intracellular reactive oxygen species. Moreover, ADMA attenuated MPP(+)-induced excessive activation of nitric oxide synthase and overproduction of NO. 4. The results of the present study suggest that the protection caused by ADMA is related to preserving mitochondrial membrane potential and attenuating the MPP(+)-induced intracellular reactive oxygen species generation through inhibiting nitric oxide synthase activity and limiting NO generation.
Tang
Xiao-Qing
XQ
Department of Physiology, Medical College, University of South China, 28 W Changsheng Road, Hengyang, Hunan, China. dfliao66@yahoo.com.cn
Li
Yu-Juan
YJ
Zhao
Jing
J
Shen
Xing-Tian
XT
Yang
Chun-Tao
CT
Fan
Li-Li
LL
Hu
Bi
B
Li
Yuan-Jian
YJ
Liao
Duan-Fan
DF
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D015655:1-Methyl-4-phenylpyridinium