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

Eizo Marutani; Masahiro Sakaguchi; Wei Chen; Kiyoshi Sasakura; Jifeng Liu; Ming Xian; Kenjiro Hanaoka; Tetsuo Nagano; Fumito Ichinose

doi:10.1039/c4md00180j

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

Eizo Marutani, Masahiro Sakaguchi, Wei Chen, Kiyoshi Sasakura, Jifeng Liu, Ming Xian, Kenjiro Hanaoka, Tetsuo Nagano, Fumito Ichinose

Research output: Contribution to journal › Article › peer-review

28 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1577-1583
Number of pages	7
Journal	MedChemComm
Volume	5
Issue number	10
DOIs	https://doi.org/10.1039/c4md00180j
Publication status	Published - 2014 Oct 1
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Organic Chemistry

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title = "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.",

author = "Eizo Marutani and Masahiro Sakaguchi and Wei Chen and Kiyoshi Sasakura and Jifeng Liu and Ming Xian and Kenjiro Hanaoka and Tetsuo Nagano and Fumito Ichinose",

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AU - Marutani, Eizo

AU - Sakaguchi, Masahiro

AU - Chen, Wei

AU - Sasakura, Kiyoshi

AU - Liu, Jifeng

AU - Xian, Ming

AU - Hanaoka, Kenjiro

AU - Nagano, Tetsuo

AU - Ichinose, Fumito

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

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

Abstract

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