Neurochemical Research

, Volume 32, Issue 9, pp 1573–1585

Nerve Growth Factor Potentiates p53 DNA Binding but Inhibits Nitric Oxide-Induced Apoptosis in Neuronal PC12 Cells

Original Paper

Abstract

NGF is recognized for its role in neuronal differentiation and maintenance. Differentiation of PC12 cells by NGF involves p53, a transcription factor that controls growth arrest and apoptosis. We investigated NGF influence over p53 activity during NO-induced apoptosis by sodium nitroprusside in differentiated and mitotic PC12 cells. NGF-differentiation produced increased p53 levels, nuclear localization and sequence-specific DNA binding. Apoptosis in mitotic cells also produced these events but the accompanying activation of caspases 1-10 and mitochondrial depolarization were inhibited during NGF differentiation and could be reversed in p53-silenced cells. Transcriptional regulation of PUMA and survivin expression were not inhibited by NGF, although NO-induced mitochondrial depolarization was dependent upon de novo gene transcription and only occurred in mitotic cells. We conclude that NGF mediates prosurvival signaling by increasing factors such as Bcl-2 and p21Waf1/Cip1 without altering p53 transcriptional activity to inhibit mitochondrial depolarization, caspase activation and apoptosis.

Keywords

NO PC12 Mitochondria Differentiation NGF p53 

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.National Center for ToxicogenomicsNational Institute of Environmental Health Sciences, National Institutes of HealthResearch Triangle ParkUSA
  2. 2.Department of Environmental and Molecular ToxicologyNorth Carolina State UniversityRaleighUSA

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