Reciprocal modulation of mitogen-activated protein kinases and mitogen-activated protein kinase phosphatase 1 and 2 in failing human myocardium.

Communal C, Colucci WS, Remondino A, Sawyer DB, Port JD, Wichman SE, Bristow MR, Singh K
J Card Fail. 2002 8 (2): 86-92

PMID: 12016632 · DOI:10.1054/jcaf.2002.32755

BACKGROUND - Mitogen-activated protein kinases (MAPKs), consisting of the ERK1/2, JNKs, and p38-kinase families, play a key role in the regulation of myocyte growth and apoptosis in vitro. The activity of MAPKs is regulated by dual-specificity MAPK phosphatases (MKPs). Because myocardial failure is associated with myocyte hypertrophy and apoptosis, MAPKs may play a pathophysiologic role in human myocardial failure.

METHODS AND RESULTS - We measured MAPKs activities and the protein levels of MAPKs and MKPs (MKP-1 and MKP-2) in the myocardium explanted at the time of transplantation from patients with end-stage failure caused by idiopathic dilated cardiomyopathy (n = 5-7). Nonfailing donor hearts (n = 5-7) were used for comparison. Although the protein levels for JNK1/2 and p38-kinase in failing hearts were not different from levels in nonfailing hearts, the activities of both were decreased (P <.05). Despite a >3-fold increase in the protein level for ERK1/2 in failing hearts, ERK1/2 activity was not increased. Expression of MKP-2 was significantly increased in failing hearts, while expression of MKP-1 was increased in 5 of 7 failing hearts as measured by Western analysis.

CONCLUSIONS - JNK1/2 and p38 activities are decreased in failing human myocardium. Increased expression of MKPs may therefore contribute to decreased MAPKs activity in failing human myocardium.

MeSH Terms (17)

Adult Blotting, Western Cardiomyopathy, Dilated Child Enzyme Activation Female Heart Failure Humans JNK Mitogen-Activated Protein Kinases Male MAP Kinase Kinase 4 Middle Aged Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases Myocardium p38 Mitogen-Activated Protein Kinases

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