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

Scott J. Cameron; Seigo Itoh; Christopher P. Baines; Changxi Zhang; Shinsuke Ohta; Wenyi Che; Michael Glassman; Jiing Dwan Lee; Chen Yan; Jay Yang; Jun Ichi Abe

doi:10.1016/j.febslet.2004.03.120

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

Scott J. Cameron, Seigo Itoh, Christopher P. Baines, Changxi Zhang, Shinsuke Ohta, Wenyi Che, Michael Glassman, Jiing Dwan Lee, Chen Yan, Jay Yang, Jun Ichi Abe

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

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.

Original language	English (US)
Pages (from-to)	255-260
Number of pages	6
Journal	FEBS Letters
Volume	566
Issue number	1-3
DOIs	https://doi.org/10.1016/j.febslet.2004.03.120
State	Published - May 21 2004
Externally published	Yes

Keywords

Big MAP kinase 1
Cardiac physiology
Hypoxia/reperfusion-injury
MAP kinase
MAPK-kinase 5
Transgenic

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2004.03.120

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@article{7dd342be121643b5a474abf4e5ccc358,

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 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.",

keywords = "Big MAP kinase 1, Cardiac physiology, Hypoxia/reperfusion-injury, MAP kinase, MAPK-kinase 5, Transgenic",

author = "Cameron, {Scott J.} and Seigo Itoh and Baines, {Christopher P.} and Changxi Zhang and Shinsuke Ohta and Wenyi Che and Michael Glassman and Lee, {Jiing Dwan} and Chen Yan and Jay Yang and Abe, {Jun Ichi}",

note = "Funding Information: This study was supported by grants from American Heart Association Pre-doctoral Fellowship AHA 0110123T (to S.J.C.), NY State Department of Health SCRIB Grant CO16891 (to J.Y.) and NIH RO1 66919–02 (to J.A.). ",

year = "2004",

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day = "21",

doi = "10.1016/j.febslet.2004.03.120",

language = "English (US)",

volume = "566",

pages = "255--260",

journal = "FEBS Letters",

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T1 - Activation of big MAP kinase 1 (BMK1/ERK5) inhibits cardiac injury after myocardial ischemia and reperfusion

AU - Cameron, Scott J.

AU - Itoh, Seigo

AU - Baines, Christopher P.

AU - Zhang, Changxi

AU - Ohta, Shinsuke

AU - Che, Wenyi

AU - Glassman, Michael

AU - Lee, Jiing Dwan

AU - Yan, Chen

AU - Yang, Jay

AU - Abe, Jun Ichi

N1 - Funding Information: This study was supported by grants from American Heart Association Pre-doctoral Fellowship AHA 0110123T (to S.J.C.), NY State Department of Health SCRIB Grant CO16891 (to J.Y.) and NIH RO1 66919–02 (to J.A.).

PY - 2004/5/21

Y1 - 2004/5/21

N2 - 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.

AB - 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.

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KW - Hypoxia/reperfusion-injury

KW - MAP kinase

KW - MAPK-kinase 5

KW - Transgenic

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

Abstract

Keywords

ASJC Scopus subject areas

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