Document Detail


Induction and nuclear accumulation of fos and jun proto-oncogenes in hypoxic cardiac myocytes.
MedLine Citation:
PMID:  8344964     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hypoxic and ischemic stresses cause a series of well documented changes in myocardial cells and tissues, including increased anaerobic glycolysis, loss of contractility, changes in lipid and fatty acid metabolism, and eventual irreversible membrane damage and cell death. In this article we describe changes in the expression and regulation of the proto-oncogenes fos and jun in cardiac myocytes exposed to severe hypoxia. The mRNAs encoding c-Fos, c-Jun, Jun-D, and Jun-B were induced within 1 h of exposure to hypoxia, increased 5-10-fold between 1 and 4 h and then declined. These inductions coincided with loss in myocyte contractility but occurred before there was irreversible cell damage or significant ATP loss. Immunostaining with anti-Fos and anti-Jun antibodies revealed the accumulation of these proteins in hypoxic cell nuclei. Pre-treatment of cells with protein kinase inhibitors significantly repressed the response at the mRNA level. We propose that hypoxic stress in these cells activates signal transduction pathways, possibly involving protein kinases, that result in the inductions of fos and jun gene families. Therefore AP1 may regulate myocardial adaptive responses to hypoxia in advance of energy depletion, cell damage, or reoxygenation.
Authors:
K A Webster; D J Discher; N H Bishopric
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  268     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1993 Aug 
Date Detail:
Created Date:  1993-09-07     Completed Date:  1993-09-07     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  16852-8     Citation Subset:  IM    
Affiliation:
Department of Cell and Molecular Biology, SRI International, Menlo Park, California 94025.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Blotting, Northern
Cell Hypoxia
Cells, Cultured
Myocardium / cytology,  metabolism*
Protein Kinase C / metabolism
Proto-Oncogene Proteins c-fos / genetics*,  metabolism
Proto-Oncogene Proteins c-jun / genetics*,  metabolism
Proto-Oncogenes*
Rats
Grant Support
ID/Acronym/Agency:
HL44578/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-fos; 0/Proto-Oncogene Proteins c-jun; EC 2.7.11.13/Protein Kinase C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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