1. Cytoprotective effects of hydrogen sulfide-releasing N-methyl-<scp>d</scp>-aspartate receptor antagonists mediated by intracellular sulfane sulfur
- Author
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Jifeng Liu, Kenjiro Hanaoka, Wei Chen, Kiyoshi Sasakura, Eizo Marutani, Masahiro Sakaguchi, Tetsuo Nagano, Fumito Ichinose, and Ming Xian
- Subjects
Pharmacology ,Programmed cell death ,Hydrogen sulfide ,Organic Chemistry ,Pharmaceutical Science ,equipment and supplies ,Biochemistry ,Neuroprotection ,Cytoprotection ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Molecular Medicine ,NMDA receptor ,Cytotoxicity ,Receptor ,Intracellular - Abstract
Hydrogen sulfide (H2S) exerts a host of biological effects ranging from cytotoxicity to cytoprotection. Cytotoxicity of H2S in neurodegenerative diseases may be mediated by N-methyl-D-aspartate receptor (NMDAR) activation. To exploit cytoprotective effects of H2S while minimizing its toxicity, we synthesized a series of H2S-releasing NMDAR antagonists and examined their effects against 1-methyl-4-phenylpyridinium (MPP+)-induced cell death, a cellular model of Parkinson's disease. We observed that cytoprotective effects of H2S-releasing NMDAR antagonists correlated with their ability to increase intracellular sulfane sulfur, but not H2S, levels. These studies suggest that H2S-donor compounds that increase intracellular sulfane sulfur levels are potentially useful neuroprotective agents against neurodegenerative diseases.
- Published
- 2014
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