Format

Send to

Choose Destination
See comment in PubMed Commons below
Neurochem Res. 2007 Sep;32(9):1573-85. Epub 2007 Jun 26.

Nerve growth factor potentiates p53 DNA binding but inhibits nitric oxide-induced apoptosis in neuronal PC12 cells.

Author information

1
National Center for Toxicogenomics, National Institute of Environmental Health Sciences, National Institutes of Health, P.O. Box 12233, Research Triangle Park, NC 27709, USA.

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 p21(Waf1/Cip1) without altering p53 transcriptional activity to inhibit mitochondrial depolarization, caspase activation and apoptosis.

PMID:
17592775
PMCID:
PMC2231119
DOI:
10.1007/s11064-007-9362-5
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Springer Icon for PubMed Central
    Loading ...
    Support Center