Essential role of p53 in TPEN-induced neuronal apoptosis

Hana Ra, Hyun Lim Kim, Han Woong Lee, Yang Hee Kim

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25 Citations (Scopus)

Abstract

Depletion of intracellular zinc with N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) induces protein synthesis-dependent apoptosis. In this study, we examined the requirement for p53 as an upstream transcription factor in TPEN-induced neuronal apoptosis. Chemical or genetic blockade of p53 markedly attenuated TPEN-induced neuronal apoptosis, while the stability and activity of p53 were increased by TPEN. In addition, expression of proapoptotic genes, PUMA and NOXA, and activation of caspase-11 were increased by TPEN in a p53-dependent manner. Inhibition of p53 blocked cytochrome C release from mitochondria to cytosol and prevented caspase-3 activation. Therefore, p53 may be an essential regulatory factor for TPEN-induced neuronal apoptosis.

Original languageEnglish
Pages (from-to)1516-1520
Number of pages5
JournalFEBS Letters
Volume583
Issue number9
DOIs
Publication statusPublished - 2009 May 6

Bibliographical note

Funding Information:
This study was supported by grants from the Korea Science & Engineering Foundation (KOSEF) (M10412000012-07N1200-01210 and R01-2006-000-10771-0(2008)).

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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