論文

査読有り
2017年

Hydrogen sulfide ameliorates zinc-induced cell death in neuroblastoma SH-SY5Y cells

FREE RADICAL RESEARCH
  • Megumi Shimoji
  • ,
  • Hirokazu Hara
  • ,
  • Tetsuro Kamiya
  • ,
  • Kensuke Okuda
  • ,
  • Tetsuo Adachi

51
11-12
開始ページ
978
終了ページ
985
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1080/10715762.2017.1400666
出版者・発行元
TAYLOR & FRANCIS LTD

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 dosedependently 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 suggest that entry of Zn2+ into cells was suppressed by NaHS. The measurement of H2S derived from NaHS by o-fluorinated-azido-capped rhodamine (Rho-N3F2), a reaction- based H2S probe, revealed that H2S levels in aqueous solutions were markedly reduced in the presence of Zn2+. This finding suggests the possibility that H2S reacts directly with Zn2+ and decreases extracellular Zn2+ levels. Taken together, we conclude that the protection of NaHS against Zn2+ cytotoxicity is exerted by inhibiting entry of Zn2+ into SH-SY5Y cells.

Web of Science ® 被引用回数 : 5

リンク情報
DOI
https://doi.org/10.1080/10715762.2017.1400666
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29092635
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000416652800009&DestApp=WOS_CPL