Age-stage specific differential activation of p38 mitogen acivated protein kinase and apoptosis in hypertensive rats
Ioannis K. Rizos · American Journal of Hypertension · 2003
Mitogen activated protein kinases (MAPK) are involved in the early development of cardiac hypertrophy but their roles are still unclear in cell fate decision. Recently we have determined the differential activation of caspase-3 (C-3) in spontaneously hypertensive rats (SHR) and its specific role in hypertrophy (H) and heat failure (HF). In this regard we correlated the activation of C-3 and p38 MAPK's during life time in SHR. Western Blotting:Left ventricles were removed, lysed and protein were separated by SDS-PAGE and electroblotted onto nitrocellulose. An antibody that recognises 32 kDa procaspase and 20 kDa C-3, was detected with chemilumiscense autoradiography. Since MAPK cascades are activated by phosphorylation events, a p38 specific phosphorylated antibody was used to detect activated p38. C-3 / procaspase-3 ratio was considered an index of C-3 activation. Digitised images were analysed with Diversity Database analysis software. p38 activation is highly elevated in the early period of hypertrophy (20 weeks of age) where C-3 activation is also increased and also during decompensation period (60-80 weeks of age) during which C-3 activation is attenuated. In SHR chronic pressure overload induces C-3 dependent apoptosis in the early hypertrophic period probably due to p38 activation. In this chronic period the role of p38 phosphorylation suggests a pro-apoptotic effect in contrast to the late decompensation and failure period during which appears as anti-apoptotic. The mismatch of p38 and C-3 induced apoptosis might be age related. See Figure 1.