title: Polysulfides protect SH-SY5Y cells from methylglyoxal-induced toxicity by suppressing protein carbonylation: A possible physiological scavenger for carbonyl stress in the brain.
abstract: The formation of advanced glycation end products (AGEs) is associated with various neurological disorders, such as Alzheimer's disease, Parkinson's disease and schizophrenia. Methylglyoxal (MG), a highly reactive dicarbonyl compound, is known to be a major precursor for AGEs in modified proteins. Thus, a scavenger of MG might provide beneficial effects by suppressing the accumulation of AGEs and the occurrence of diseases induced by carbonyl stress. Meanwhile, polysulfides, one of the typical bound sulfur species, are oxidized forms of hydrogen sulfide (H2S) and may play a variety of roles in the brain. Herein, we assessed the scavenging ability of polysulfides against neuronal carbonyl stress induced by MG. First, we showed that polysulfides could protect differentiated (df)-SH-SY5Y cells from MG-induced cytotoxicity. When cells were pretreated with polysulfides, MG-induced cytotoxicity was attenuated with a rapid decrease in intracellular MG levels. Moreover, we found that polysulfides significantly suppressed the formation of MG-modified proteins in df-SH-SY5Y cells. Although polysulfide treatment increased endogenous GSH levels in the neuronal cells, its effects on MG-induced cytotoxicity were not affected by GSH concentration. Our results demonstrated that polysulfides had the direct potentials to protect neuronal cells against MG separate to the enzymatic detoxification system that required GSH.
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Koike
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Kayama
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Komine
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Tanaka
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Nishimoto
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Synthetic Organic Chemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kishida
authors.affiliation: Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan. Electronic address: yo@my-pharm.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ogasawara
mesh_terms: D000704:Analysis of Variance; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects*; D011765:Pyruvaldehyde / Q000633:toxicity*; D013440:Sulfides / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D013440:Sulfides; D011765:Pyruvaldehyde; C032915:polysulfide; D005978:Glutathione
keywords: Bound sulfur species; Carbonyl stress; Methylglyoxal; Neurological disorder; Polysulfides; Schizophrenia