OCR Text |
Show UNDERGRADUATE RESEARCH ABSTRACTS SPRING 2007 Josh Smith J. David Symons 71 Acute Exercise Increases Intracellular Signaling Kinase Activity That Can Phosphorylate eNOS In Mice JC Liljenquist, Josh Smith, S McMillin (JD Symons) Department of Exercise and Sports Science University of Utah Functional hyperemia in metabolically active tissues occurs during dynamic exercise so that oxygen supply can meet oxygen demand. Blood flow elevations are associated with increases in shear/mechanical forces along the endothelial surface of the arterial wall. Activated endothelial mechanoreceptors may stimulate downstream intracellular signaling pathways that phosphorylate (p) (e.g., activate) endothelial nitric oxide synthase (eNOS) and evoke nitric oxide (NO) production. The precise molecular mechanism(s) responsible for this are unclear. Results from cultured endothelial cells and isolated blood vessels report that mechanical forces and increased perfusion rate phosphorylate intracellular signaling kinases [e.g., Akt/protein kinase B (Akt), protein kinase A (PKA), and/or adenosine monophosphate-activated protein kinase (AMPK)], which can phosphorylate eNOS. We hypothesized that acute exercise activates intracellular signaling kinases and eNOS in the vasculature. Fifteen-week-old male mice completed 45.8 ± 1.7 min of treadmill-running (20 m/min @ 5% grade; Ex, n=9) or were exposed to treadmill noise/vibration (Sed, n=8). Aorta, iliac, and femoral arteries were isolated from Ex and Sed mice to assess p-eNOS at serine (S) S1177 (p-eNOS S1177), p-Akt at S473 (p-Akt S473), p-Akt at threonine (T) 308 (p-Akt T308), p-cAMP response element binding protein at S133 (p-CREB S133; a downstream target of PKA), and p-AMPK at T172 (p-AMPK T172). p-eNOS S1177, p-Akt S473, and p-CREB S133 increased (p<0.05) by 2.1, 2.6, and 1.5-fold, respectively, in iliac/femoral arteries from Ex vs. Sed mice, while the increases in p-Akt T308 and p-AMPK T172 were non-significant between groups. Results were similar between aortae and iliac/femoral arteries. Because maximal Akt activity requires both S473 and T308 to be phosphorylated, PKA appears to be an important regulator of p-eNOS S1177 in the vasculature. |