| First Author | Banerjee SK | Year | 2007 |
| Journal | Biochem Biophys Res Commun | Volume | 360 |
| Issue | 2 | Pages | 381-7 |
| PubMed ID | 17597581 | Mgi Jnum | J:123005 |
| Mgi Id | MGI:3716235 | Doi | 10.1016/j.bbrc.2007.06.067 |
| Citation | Banerjee SK, et al. (2007) A PRKAG2 mutation causes biphasic changes in myocardial AMPK activity and does not protect against ischemia. Biochem Biophys Res Commun 360(2):381-7 |
| abstractText | Dominant mutations in the gamma2 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(alpha2DN) mice, which overexpress a dominant negative mutant of the AMPK alpha2 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. |
