Activation of big MAP kinase 1 (BMK1/ERK5) inhibits cardiac injury after myocardial ischemia and reperfusion

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Abstract

Big MAP kinase 1 (BMK1/ERK5) plays a critical role in pre-natal development of the cardiovascular system and post-natal eccentric hypertrophy of the heart. Of the two isoforms upstream of MAPK-kinase 5 (MEK5) known to exist, only the longer MEK5α isoform potently activates BMK1. We generated cardiac-specific constitutively active form of the MEK5α (CA-MEK5α transgenic (Tg) mice), and observed a 3 to 4-fold increase in endogenous BMK1 activation and hyperphosphorylation of connexin 43 in the ventricles of the Tg compared to wild-type mice. The CA-MEK5α-Tg-mice demonstrated a profoundly accelerated recovery of left ventricular developed pressure after ischemia/reperfusion. We propose a novel role for BMK1 in protecting the heart from ischemia/reperfusion-induced cardiac injury. © 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

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Cameron, S. J., Itoh, S., Baines, C. P., Zhang, C., Ohta, S., Che, W., … Abe, J. I. (2004). Activation of big MAP kinase 1 (BMK1/ERK5) inhibits cardiac injury after myocardial ischemia and reperfusion. FEBS Letters, 566(1–3), 255–260. https://doi.org/10.1016/j.febslet.2004.03.120

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