title: Cytoprotective effects of hydrogen sulfide-releasingN-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 byN-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.
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Eizo
authors.initials: E
authors.lastname: Marutani
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: Department of Chemistry, Washington State University, Pullman, Washington.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Sasakura
authors.affiliation: Aberjona Laboratories, Inc., Beverly, MA.
authors.forename: Jifeng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Washington State University, Pullman, Washington.
authors.forename: Ming
authors.initials: M
authors.lastname: Xian
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Hanaoka
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nagano
authors.affiliation: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Fumito
authors.initials: F
authors.lastname: Ichinose