Transient activation of p38 MAP kinase and up-regulation of Pim-1 kinase in cardiac hypertrophy despite no activation of AMPK.
AMP-activated protein kinase (AMPK), is an important regulator of cardiac metabolism, but its role is not clearly understood in pressure overload induced hypertrophy. In addition, the relationship between AMPK and other important protein kinases such as p38 MAP kinase, Akt and Pim-1 is unclear. Thus we studied the time course of AMPK activity and phosphorylation of Thr-172 of its alpha-subunit during the development of cardiac hypertrophy. In parallel, we examined the expression and activation of key kinases known to be involved in cardiac hypertrophy that could interact with AMPK (i.e. p38 MAP kinase, Akt and Pim-1). Male C57BL/6J mice underwent sham or transverse aortic constriction (TAC) surgery and the hearts were harvested 2, 4, 6 and 8 weeks later. Despite significant left ventricular (LV) hypertrophy, LV dilation and impaired LV contractile function at all time points in TAC compared to sham mice, the activity and phosphorylation of AMPK were similar to sham. In contrast, p38 and Pim-1 protein expression was transiently increased in TAC mice at 2 and 4 weeks and at 2, 4 and 6 weeks, respectively. In addition, p38 activation by phosphorylation was also transiently increased at 2 to 6 weeks. There were no differences between sham and TAC mice in p38, Akt or Pim-1 at 8 weeks. In conclusion, TAC resulted in a transient up-regulation in the expression of p38 and Pim-1 despite no activation of AMPK or Akt.
Lei
Biao
B
Division of Cardiology, Department of Medicine, University of Maryland Baltimore Medical Center, 20 Penn St., HSF-II, Room S022 Baltimore, MD 21201, USA.
Chess
David J
DJ
Keung
Wendy
W
O'Shea
Karen M
KM
Lopaschuk
Gary D
GD
Stanley
William C
WC
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D004789:Enzyme Activation; D017379:Hypertrophy, Left Ventricular / Q000201:enzymology* / Q000401:mortality; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D051573:Proto-Oncogene Proteins c-pim-1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
C496636:Pim1 protein, mouse; D051573:Proto-Oncogene Proteins c-pim-1; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases