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Cytoprotective effects of hydrogen sulfide-releasing N-methyl-D-aspartate receptor antagonists are mediated by intracellular sulfane sulfur.

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 effect 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 are potentially useful neuroprotective agents against neurodegenerative diseases.

SUBMITTER: Marutani E 

PROVIDER: S-EPMC4242466 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Cytoprotective effects of hydrogen sulfide-releasing <i>N</i>-methyl-D-aspartate receptor antagonists are mediated by intracellular sulfane sulfur.

Marutani Eizo E   Sakaguchi Masahiro M   Chen Wei W   Sasakura Kiyoshi K   Liu Jifeng J   Xian Ming M   Hanaoka Kenjiro K   Nagano Tetsuo T   Ichinose Fumito F  

MedChemComm 20141001 10

Hydrogen sulfide (H<sub>2</sub>S) exerts a host of biological effects ranging from cytotoxicity to cytoprotection. Cytotoxicity of H<sub>2</sub>S in neurodegenerative diseases may be mediated by <i>N</i>-methyl-D-aspartate receptor (NMDAR) activation. To exploit cytoprotective effects of H<sub>2</sub>S while minimizing its toxicity, we synthesized a series of H<sub>2</sub>S-releasing NMDAR antagonists and examined their effects against 1-methyl-4-phenylpyridinium (MPP<sup>+</sup>)-induced cell d  ...[more]

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