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Mitogen –Activated Protein Kinases and Septic Cardiomyopathy
Author(s) -
Zetoune Firas S,
Hoesel Laszlo M,
Neiderbichler Andreas D.,
Flierl Michael A.,
Rittirsch Daniel,
Nadeau Brian,
Sarma J Vidya,
Ward Peter A
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1150-c
Subject(s) - phospholamban , sepsis , mapk/erk pathway , p38 mitogen activated protein kinases , kinase , protein kinase a , phosphorylation , signal transduction , mitogen activated protein kinase , microbiology and biotechnology , biology , medicine , chemistry
In human sepsis and in cecal ligation and puncture (CLP)‐induced sepsis in rodents, progressive heart failure, as characterized by falling left ventricular pressures and cardiac output, occurs. Human sepsis is associated with the appearance in serum of complement activation products (anaphylatoxins C3a and C5a). In response to pathophysiological stress (such as in sepsis), signaling through the G‐protein coupled receptors (such as of C3a and C5a) found on cell membranes in the heart results in the activation of intermediate signaling pathways in cardiomyocytes (CMs) including mitogen–activated protein kinases (MAPKs) and protein kinase C, which in turn modulate transcriptional factors that amplify gene expression. Studies have shown that the three major MAPKs pathways (ERK/MAPK (p42/44), SAPK/JNK (1/2) and p38) are differentially regulated during heart disease. We therefore evaluated the activation status of these pathways in isolated CMs as a function of time after the onset of CLP induced sepsis in rats by Western blotting. Peak activation (as assessed by protein phosphorylation) occurred in all three MAPK pathways in CMs between 12 and 48 hour after CLP. In addition, we found that activation of phospholamban (PLB), an important regulator of calcium homeostasis in CMs, peaked 12 hour after CLP. The relationship between activation of MAPKs and PLB to development of cardiac myopathy during sepsis remains to be determined. These data indicate that during CLP induced sepsis extensive MAPK activation occurs in CMs.