Role of mitogen-activated protein kinase in cardiac hypertrophy and heart failure.


BACKGROUND Mitogen-activated protein kinases (MAPKs) are involved in the regulation of various cellular responses including cell proliferation, differentiation and survival. Although MAPKs are activated by MAPK kinase and inactivated by phosphatases, different types of MAPKs, including extracellular signal-regulated kinases (ERK1 and 2), c-jun N-terminal protein kinases (JNK) and p38 kinases are known to participate in different signalling pathways. This article will review some salient features of the regulation and function of different forms of MAPKs in the heart. Furthermore, the status of cardiac MAPKs under different pathophysiological conditions will be described. OBSERVATIONS A wide variety of external stimuli are known to activate MAPKs, which are then translocated from the cytoplasm to the nucleus and regulate cardiac gene expression by phosphorylating various transcriptional factors. By virtue of the involvement of ERK1/2 in hypertrophic response and of the stress-activated JNKs and p38 kinases in the process of apoptosis, MAPKs are considered to be intimately involved in cardiac remodelling. Both growth factors and phorbol esters have been shown to strongly activate ERK1/2, whereas the activation of JNKs and p38 kinases by these agents is weak. Although ischemia-reperfusion activates all types of MAPKs, JNKs and p38 kinases are mainly proapoptotic, whereas ERK1/2 are antiapoptotic. CONCLUSIONS The activation of ERK1/2 is involved in signal transduction pathways associated with cardiac hypertrophy; however, the exact status of MAPKs in heart failure remains to be clearly defined. While both JNKs and p38 kinases appear to participate in the genesis of ischemia-reperfusion injury, ERK1/2 are considered to be cytoprotective.

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@article{Zhang2003RoleOM, title={Role of mitogen-activated protein kinase in cardiac hypertrophy and heart failure.}, author={Weihua Zhang and Vijayan Elimban and Mohinder S. Nijjar and Suresh Kumar Gupta and Naranjan S. Dhalla}, journal={Experimental and clinical cardiology}, year={2003}, volume={8 4}, pages={173-83} }