title: Activation of big MAP kinase 1 (BMK1/ERK5) inhibits cardiac injury after myocardial ischemia and reperfusion.
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 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.
authors.affiliation: Department of Pharmacology/Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Cameron
authors.forename: Seigo
authors.initials: S
authors.lastname: Itoh
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Baines
authors.forename: Changxi
authors.initials: C
authors.lastname: Zhang
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Ohta
authors.forename: Wenyi
authors.initials: W
authors.lastname: Che
authors.forename: Michael
authors.initials: M
authors.lastname: Glassman
authors.forename: Jiing-Dwan
authors.initials: JD
authors.lastname: Lee
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.forename: Jay
authors.initials: J
authors.lastname: Yang
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Abe
mesh_terms: 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
chemical_list: D018031:Connexin 43; D007527:Isoenzymes; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases