Issue 10, 2014
From the journal:

MedChemComm

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

Eizo Marutani,*a   Masahiro Sakaguchi,a   Wei Chen,b   Kiyoshi Sasakura,c   Jifeng Liu,d   Ming Xian,b   Kenjiro Hanaoka,c   Tetsuo Naganoc  and  Fumito Ichinosea  

* 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

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

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

E. Marutani, M. Sakaguchi, W. Chen, K. Sasakura, J. Liu, M. Xian, K. Hanaoka, T. Nagano and F. Ichinose, Med. Chem. Commun., 2014, 5, 1577 DOI: 10.1039/C4MD00180J

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