Polysulfide exerts a protective effect against cytotoxicity caused by t-buthylhydroperoxide through Nrf2 signaling in neuroblastoma cells.
Polysulfide is a bound sulfur species derived from endogenous H2S. When mouse neuroblastoma, Neuro2A cells were exposed to tert-butyl hydroperoxide after treatment with polysulfide, a significant decline in cell toxicity was observed. Rapid uptake of polysulfides induced translocation of Nrf2 into the nucleus, resulting in acceleration of GSH synthesis and HO-1 expression. We demonstrated that polysulfide reversibly modified Keap1 to form oxidized dimers and induced the translocation of Nrf2. Moreover, polysulfide treatment accelerated Akt phosphorylation, which is a known pathway of Nrf2 phosphorylation. Thus, polysulfide may mediate the activation of Nrf2 signaling, thereby exerting protective effects against oxidative damage in Neuro2A cells.
Department of Hygienic Chemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
Shin
S
Koike
Yuki
Y
Ogasawara
Norihiro
N
Shibuya
Hideo
H
Kimura
Kazuyuki
K
Ishii
D000818:Animals; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013440:Sulfides / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D013440:Sulfides; C032915:polysulfide; D020122:tert-Butylhydroperoxide; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
Bound sulfur; DTT; GSH; HO-1; Keap1; Kelch-like ECH-associated protein-1; Nrf2; Oxidative stress; Phosphorylation; Polysulfide; dithiothreitol; glutathione; heme oxygenase 1; nuclear factor-erythroid 2 p45-related factor 2; t-BHP; tert-buthylhydroperoxide