https://scholars.lib.ntu.edu.tw/handle/123456789/389122
標題: | Depletion of arginine by recombinant arginine deiminase induces nnos-activated neurotoxicity in neuroblastoma cells | 作者: | Ko, Chun-Jung LI-JIUAN SHEN Lin, Shan-Erh Wu, Fe-Lin Lin Huang, Cheng-Chung Lin, Hsin-Ying Wei, Ming-Feng Juan, Chun-Pai Lan, Shao-Wei Shyu, Hsin-Yi Wu, Shang-Ru Hsiao, Pei-Wen Shun, Chia-Tung Lee, Ming-Shyue |
公開日期: | 2014 | 卷: | 2014 | 來源出版物: | BioMed Research International | 摘要: | The abnormal regulation of inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) is associated with neurodegenerative disorders. Recombinant arginine deiminase (rADI) is a selective NO modulator of iNOS and eNOS in endothelial cells, and it also exhibits neuroprotective activity in an iNOS-induced neuron-microglia coculture system. However, the effect of rADI on nNOS remains unknown. Addressing this issue is important for evaluating the potential application of rADI in neurodegenerative diseases. SH-SY5Y cells were treated with N-methyl-D-aspartic acid (NMDA) to activate nNOS. NMDA increased NO production by 39.7 ± 3.9% via nNOS under arginine-containing conditions, but there was no significant increase in both arginine-free and rADI pretreated arginine-containing (citrulline) buffer. Subsequently, neither NMDA nor rADI alone caused cytotoxicity, whereas cotreatment with NMDA and rADI resulted in dissipation of the cell mitochondrial membrane potential and decreased cell viability. The mechanism of rADI cytotoxicity in the presence of NMDA is caused by the inhibition of NO production via nNOS mediated by the NMDA receptor, which was abolished when extracellular arginine was absent, even in the presence of citrulline. rADI not only reduced NO production but also caused cellular toxicity in nNOS-activated SH-SY5Y cells, suggesting a dual role for rADI in NOS-mediated neurotoxicity. ? 2014 Shan-Erh Lin et al. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84929051756&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/389122 |
DOI: | 10.1155/2014/589424 | SDG/關鍵字: | arginine; arginine deiminase; n methyl dextro aspartic acid; neuronal nitric oxide synthase; nitric oxide; arginine; arginine deiminase; hydrolase; inducible nitric oxide synthase; n methylaspartic acid; neuronal nitric oxide synthase; nitric oxide; NOS2 protein, human; recombinant protein; Article; cell activation; cell protection; cell viability; controlled study; human; human cell; mitochondrial membrane potential; neuroblastoma cell; neurotoxicity; biosynthesis; cell survival; culture technique; drug effects; enzymology; genetics; metabolism; nerve cell; Neurodegenerative Diseases; pathology; Arginine; Cell Culture Techniques; Cell Survival; Humans; Hydrolases; Membrane Potential, Mitochondrial; N-Methylaspartate; Neurodegenerative Diseases; Neurons; Nitric Oxide; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type II; Recombinant Proteins |
顯示於: | 藥學系 |
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