Polysulfide exerts a protective effect against cytotoxicity caused by t‐buthylhydroperoxide through Nrf2 signaling in neuroblastoma cells

Abstract

a b s t r a c tPolysulfide is a bound sulfur species derived from endogenous H 2 S. 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.

The Therapeutic Potential of Cystathionine β-Synthetase/Hydrogen Sulfide Inhibition in Cancer

“…For example, pretreatment of cells or animals with H 2 S can induce the expression of protective genes and pathways (e.g., ones governed by the antioxidant master switch Nrf2), resulting in altered cellular phenotypes at later time points (i.e., where ambient H 2 S levels are no longer detectable, the classical phenomenon of ''preconditioning'') (15,143). While these mechanisms are primarily studied in the context of cardiovascular biology, Koike et al have shown that pretreatment of cancer cells with polysulfides (which have H 2 S-donating properties, as well as many other pharmacological actions) can induce Nrf2-dependent protective phenotypes (64).…”

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“…As CXCL13 and MARCO genes are immune mediators in response to inflammation, exposure to AgNPs may change their gene expression. Moreover, glutathione synthetase (GSS) can synthesize glutathione (GSH) potentially to inhibit oxidative stress and prevent cellular damage from free radicals and peroxides (Koike et al, 2013), and AgNPs exposure probably alters GSS gene expression.…”

Delivery of Hypoxia-Inducible Heme Oxygenase-1 Gene for Site-Specific Gene Therapy in the Ischemic Stroke Animal Model

“…2b). It was previously reported that the endogenous HO-1 was induced in the Neuro2A cells by oxidative stress such as hypoxia (29,30). The cells transfected with pEmtpy also showed the increased HO-1 expression under hypoxia after 24 and 48 h of incubation (3.7-fold induction at 48 h).…”