Cytoprotective effects of hydrogen sulfide-releasing N-methyl-D-aspartate receptor antagonists mediated by intracellular sulfane sulfur (original) (raw)

* Corresponding authors

a Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
E-mail: emarutani@mgh.harvard.edu

b Department of Chemistry, Washington State University, Pullman, Washington, USA

c Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

d Aberjona Laboratories, Inc., Beverly, MA, USA

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.

Graphical abstract: Cytoprotective effects of hydrogen sulfide-releasing N-methyl-d-aspartate receptor antagonists mediated by intracellular sulfane sulfur

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Article information

DOI

https://doi.org/10.1039/C4MD00180J

Article type

Concise Article

Submitted

21 Apr 2014

Accepted

29 Jul 2014

First published

26 Aug 2014

Download Citation

Med. Chem. Commun., 2014,5, 1577-1583

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