A PRKAG2 mutation causes biphasic changes in myocardial AMPK activity and does not protect against ischemia

Sanjay K Banerjee; Ravi Ramani; Samir Saba; Jennifer Rager; Rong Tian; Michael A Mathier; Ferhaan Ahmad

doi:10.1016/j.bbrc.2007.06.067

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A PRKAG2 mutation causes biphasic changes in myocardial AMPK activity and does not protect against ischemia

Journal article

Peer reviewed

A PRKAG2 mutation causes biphasic changes in myocardial AMPK activity and does not protect against ischemia

Sanjay K Banerjee, Ravi Ramani, Samir Saba, Jennifer Rager, Rong Tian, Michael A Mathier and Ferhaan Ahmad

Biochemical and biophysical research communications, Vol.360(2), pp.381-387

2007

DOI: 10.1016/j.bbrc.2007.06.067

PMID: 17597581

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Abstract

Dominant mutations in the γ2 regulatory subunit of AMP-activated protein kinase (AMPK), encoded by the gene PRKAG2, cause glycogen storage cardiomyopathy. We sought to elucidate the effect of the Thr400Asn (T400N) human mutation in a transgenic mouse (TG T400N) on AMPK activity, and its ability to protect the heart against ischemia–reperfusion injury. TG T400N hearts had markedly vacuolated myocytes, excessive accumulation of glycogen, hypertrophy, and preexcitation. Early activation of myocardial AMPK, followed by depression, and then recovery to wild-type levels was observed. AMPK activity correlated inversely with glycogen content. Partial rescue of the phenotype was observed when TG T400N mice were crossbred with TG α2DN mice, which overexpress a dominant negative mutant of the AMPK α2 catalytic subunit. TG T400N hearts had greater infarct sizes and apoptosis when subjected to ischemia–reperfusion. Increased AMPK activity is responsible for glycogen storage cardiomyopathy. Despite high glycogen content, the TG T400N heart is not protected against ischemia–reperfusion injury.

Cardiac hypertrophy

AMPK

Glycogen cardiomyopathy

Myocardial ischemia–reperfusion

Transgenic mouse model

Details

Title: Subtitle: A PRKAG2 mutation causes biphasic changes in myocardial AMPK activity and does not protect against ischemia
Creators: Sanjay K Banerjee - Cardiovascular Institute, Department of Medicine, University of Pittsburgh, 200 Lothrop Street, Scaife Hall, S558, Pittsburgh, PA 15213, USA
Ravi Ramani - Cardiovascular Institute, Department of Medicine, University of Pittsburgh, 200 Lothrop Street, Scaife Hall, S558, Pittsburgh, PA 15213, USA
Samir Saba - Cardiovascular Institute, Department of Medicine, University of Pittsburgh, 200 Lothrop Street, Scaife Hall, S558, Pittsburgh, PA 15213, USA
Jennifer Rager - Cardiovascular Institute, Department of Medicine, University of Pittsburgh, 200 Lothrop Street, Scaife Hall, S558, Pittsburgh, PA 15213, USA
Rong Tian - Cardiovascular Division, Brigham and Women’s Hospital, Boston, MA 02115, USA
Michael A Mathier - Cardiovascular Institute, Department of Medicine, University of Pittsburgh, 200 Lothrop Street, Scaife Hall, S558, Pittsburgh, PA 15213, USA
Ferhaan Ahmad - Cardiovascular Institute, Department of Medicine, University of Pittsburgh, 200 Lothrop Street, Scaife Hall, S558, Pittsburgh, PA 15213, USA
Resource Type: Journal article
Publication Details: Biochemical and biophysical research communications, Vol.360(2), pp.381-387
Publisher: Elsevier Inc
DOI: 10.1016/j.bbrc.2007.06.067
PMID: 17597581
ISSN: 0006-291X
eISSN: 1090-2104
Language: English
Date published: 2007
Academic Unit: Radiology; Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984025679502771

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