Hydrogen sulfide ameliorates zinc-induced cell death in neuroblastoma SH-SY5Y cells
Abstract
Previous reports have demonstrated that excess zinc (Zn2+) released from nerve terminals following cerebral ischemia causes brain injury. Therefore, the disturbance of Zn2+ homeostasis in the brain is thought to be closely linked to neurotoxicity. Recently, hydrogen sulfide (H2S), a gaseous mediator, has been reported to ameliorate ischemic brain injury. However, its mechanism is not fully understood. In this study, we examined whether sodium hydrogen sulfide (NaHS), an H2S donor, protects against Zn2+ cytotoxicity using human neuroblastoma SH-SY5Y cells. NaHS dose-dependently prevented cell death caused by Zn2+ exposure. Treatment of cells with NaHS just before Zn2+ exposure exerted the most potent protection. Zn2+ induced loss of intracellular NAD+ and ATP and mitochondrial dysfunctions, resulting in cytotoxicity associated with failure of energy production; however, NaHS prevented these Zn2+-induced events. In addition, NaHS suppressed Zn2+-dependent activation of metal-responsive transcription factor-1 and induction of metallothionein gene expression. Zn2+ imaging with the Zn2+-specific fluorescent indicator FluoZin-3 revealed that NaHS abolished the elevation of intracellular Zn2+ levels after Zn2+ exposure. These results ...Continue Reading
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