Asymmetrical dimethylarginine antagonizes glutamate-induced apoptosis in PC12 cells.
Overproduction of nitric oxide (NO) plays an important role in glutamate-induced excitotoxicity. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor. The aim of this study is to explore whether ADMA antagonizes the excitotoxicity of glutamate to neuronal cells and the underlying molecular mechanisms. In this work, we investigated the effects of ADMA on glutamate-induced toxicity in neuronal cells by studying PC12 cells, a clonal rat pheochromocytoma cell line. We show that ADMA obviously protects PC12 cells against glutamate-induced cytotoxicity and apoptosis. We also found that ADMA treatment results in prevention of glutamate-induced mitochondrial membrane potential loss and caspase-3 activation. Moreover, ADMA prevents glutamate-caused down-regulation of bcl-2 protein expression. These results indicate that ADMA protects against glutamate-induced apoptosis and excitotoxicity and the underlying mechanism may be involved in preservation of mitochondrial function by up-regulating the expression of bcl-2. Our study suggests a promising future of ADMA-based therapies for neuropathologies associated with an excess of NO.
Department of Neurology, Third Clinical Hospital, China Three Gorges University, 60 Qiaohu 1st Road, 443002 Yichang, China. ycwangxy@163.com
Xiang-Yu
XY
Wang
Jing
J
Zhao
Hong-Wei
HW
Yang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053148:Caspase 3 / Q000032:analysis; D018698:Glutamic Acid / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats
D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D018698:Glutamic Acid; C018524:N,N-dimethylarginine; D001120:Arginine; D053148:Caspase 3