Activation of big MAP kinase 1 (BMK1/ERK5) inhibits cardiac injury after myocardial ischemia and reperfusion.
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 MEK5alpha isoform potently activates BMK1. We generated cardiac-specific constitutively active form of the MEK5alpha (CA-MEK5alpha 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-MEK5alpha-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.
Cameron
Scott J
SJ
Department of Pharmacology/Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Itoh
Seigo
S
Baines
Christopher P
CP
Zhang
Changxi
C
Ohta
Shinsuke
S
Che
Wenyi
W
Glassman
Michael
M
Lee
Jiing-Dwan
JD
Yan
Chen
C
Yang
Jay
J
Abe
Jun-ichi
J
D000818:Animals; D020169:Caspases / Q000378:metabolism; D018031:Connexin 43 / Q000378:metabolism; D004452:Echocardiography / Q000379:methods; D004789:Enzyme Activation; D015870:Gene Expression; D006321:Heart / Q000033:anatomy & histology / Q000503:physiopathology; D007527:Isoenzymes; D051379:Mice; D008822:Mice, Transgenic; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000201:enzymology* / Q000235:genetics; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control*; D010766:Phosphorylation; D016276:Ventricular Function / Q000502:physiology
D018031:Connexin 43; D007527:Isoenzymes; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases