Cytoprotective effects of hydrogen sulfide-releasing N-methyl-d-aspartate receptor antagonists 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 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.