論文

査読有り
2009年8月

Zinc Induces Expression of the BH3-only Protein PUMA Through p53 and ERK Pathways in SH-SY5Y Neuroblastoma Cells

NEUROCHEMICAL RESEARCH
  • Hirokazu Hara
  • ,
  • Tetsuro Kamiya
  • ,
  • Tetsuo Adachi

34
8
開始ページ
1498
終了ページ
1506
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s11064-009-9937-4
出版者・発行元
SPRINGER/PLENUM PUBLISHERS

Accumulating evidence suggests that zinc (Zn2+) contributes to neuronal death in pathologic states such as ischemia. p53-upregulated modulator of apoptosis (PUMA), which is a BH3-only protein, is known to promote apoptosis through a tumor suppressor p53-dependent and -independent mechanism. In this study, we examined the effect of Zn2+ on the induction of the PUMA gene in human neuroblastoma SH-SY5Y cells. The expression of PUMA was induced by Zn2+ in a dose- and time-dependent manner. A reporter assay revealed that Zn2+ activated the PUMA promoter. In addition, the mutation of the p53 binding site in the PUMA promoter region reduced promoter activation by Zn2+. These findings suggest that p53 participates in Zn2+-induced PUMA expression. Furthermore, we also demonstrated here that Zn2+ stimulates the phosphorylation of ERK and that the MEK-ERK pathway inhibitor, U0126, suppressed Zn2+-induced PUMA expression. Taken together, these results indicate that Zn2+ regulates the induction of PUMA through p53 and ERK pathways.

Web of Science ® 被引用回数 : 9

リンク情報
DOI
https://doi.org/10.1007/s11064-009-9937-4
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/19241161
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000267041700018&DestApp=WOS_CPL