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Asymmetrical Dimethylarginine Antagonizes Glutamate-Induced Apoptosis in PC12 Cells

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Abstract

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.

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Authors and Affiliations

  1. Department of Neurology, Third Clinical Hospital, China Three Gorges University, 60 Qiaohu 1st Road, 443002, Yichang, China

    Xiang-Yu Wang

  2. Department of Neurology, Gezhouba Central Hospital, 443002, Yichang, China

    Xiang-Yu Wang

  3. Department of Physiology, Medical College, University of south China, Hengyang, 421001, Hunan, China

    Jing Zhao

  4. Department of Physiology, college of medical sciences, China Three Gorges University, 443002, Yichang, China

    Hong-Wei Yang

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  1. Xiang-Yu Wang
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  2. Jing Zhao
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Correspondence to Xiang-Yu Wang.

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Wang, XY., Zhao, J. & Yang, HW. Asymmetrical Dimethylarginine Antagonizes Glutamate-Induced Apoptosis in PC12 Cells. J Mol Neurosci 49, 89–95 (2013). https://doi.org/10.1007/s12031-012-9897-z

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  • DOI: https://doi.org/10.1007/s12031-012-9897-z

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