Ventricular myocytes are exposed to various pathologically important cell stresses in vivo. In vitro,extreme stresses (sorbitol-induced hyperosmotic shock in the presence or absence of okadaic acid, and anisomycin) were applied to ventricular myocytes cultured from neonatal rat hearts to induce a robust activation of the 46 and 54 kDa stress-activated protein kinases (SAPKs). These activities were increased in nuclear extracts of cells in the absence of any net import of SAPK protein. Phosphorylation of ATF2 and c-Jun was increased as shown by the appearance of reduced-mobility species on SDS/PAGE, which were sensitive to treatment with protein phosphatase 2A. Hyperosmotic shock and anisomycin had no effect on the abundance of ATF2. In contrast, cell stresses induced a greater than 10-fold increase in total c-Jun immunoreactivity detected on Western blots with antibody to c-Jun (KM-1). Cycloheximide did not inhibit this increase, which we conclude represents phosphorylation of c-Jun. This conclusion was supported by use of a c-Jun(phospho-Ser-73) antibody. Immunostaining of cells also showed increases in nuclear phospho-c-Jun in response to hyperosmotic stress. Severe stress (hyperosmotic shock+okadaic acid for 2 h) induced proteins (migrating at approx. 51 and 57 kDa) that cross-reacted strongly with KM-1 antibodies in both the nucleus and the cytosol. These may represent forms of c-Jun that had undergone further modification. These studies show that stresses induce phosphorylation of transcription factors in ventricular myocytes and we suggest that this response may be pathologically relevant.
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Research Article|
August 01 1997
Cell stress-induced phosphorylation of ATF2 and c-Jun transcription factors in rat ventricular myocytes
Angela CLERK;
Angela CLERK
1Division of Cardiac Medicine, Imperial College School of Medicine at N.H.L.I., Dovehouse Street, London SW3 6LY, U.K.
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Peter H. SUGDEN
Peter H. SUGDEN
1
1Division of Cardiac Medicine, Imperial College School of Medicine at N.H.L.I., Dovehouse Street, London SW3 6LY, U.K.
1To whom correspondence should be addressed.
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Publisher: Portland Press Ltd
Received:
March 21 1997
Accepted:
April 11 1997
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1997
1997
Biochem J (1997) 325 (3): 801–810.
Article history
Received:
March 21 1997
Accepted:
April 11 1997
Citation
Angela CLERK, Peter H. SUGDEN; Cell stress-induced phosphorylation of ATF2 and c-Jun transcription factors in rat ventricular myocytes. Biochem J 1 August 1997; 325 (3): 801–810. doi: https://doi.org/10.1042/bj3250801
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