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.