| First Author | Matheny RW Jr | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 482 |
| Issue | 4 | Pages | 1420-1426 |
| PubMed ID | 27965101 | Mgi Jnum | J:241714 |
| Mgi Id | MGI:5903541 | Doi | 10.1016/j.bbrc.2016.12.051 |
| Citation | Matheny RW Jr, et al. (2017) Skeletal muscle PI3K p110beta regulates expression of AMP-activated protein kinase. Biochem Biophys Res Commun 482(4):1420-1426 |
| abstractText | Skeletal muscle metabolic homeostasis is maintained through numerous biochemical and physiological processes. Two principal molecular regulators of skeletal muscle metabolism include AMP-activated protein kinase (AMPK) and phosphatidylinositol 3-kinase (PI3K); however, PI3K exists as multiple isoforms, and specific metabolic actions of each isoform have not yet been fully elucidated in skeletal muscle. Given this lack of knowledge, we performed a series of experiments to define the extent to which PI3K p110beta mediated expression and (or) activation of AMPK in skeletal muscle. To determine the effect of p110beta inhibition on AMPK expression and phosphorylation in cultured cells, C2C12 myoblasts were treated with a pharmacological inhibitor of p110beta (TGX-221), siRNA against p110beta, or overexpression of kinase-dead p110beta. Expression and phosphorylation of AMPK were unaffected in myoblasts treated with TGX-221 or expressing kinase-dead p110beta. However, expressions of total and phosphorylated AMPK at T172 were reduced in myoblasts treated with p110beta siRNA. When normalized to expression of total AMPK, phosphorylation of AMPK S485/491 was elevated in p110beta-deficient myoblasts. Similar results were observed in tibialis anterior muscle from mice with conditional deletion of p110beta (p110beta-mKO mice). Analysis of AMPK transcript expression revealed decreased expression of Prkaa2 in p110beta-deficient myoblasts and in p110beta-mKO muscle. Loss of p110beta had no effect on oligomycin-stimulated phosphorylation of AMPK or phosphorylated Acetyl-CoA carboxylase (ACC), although oligomycin-induced AMPK and ACC phosphorylation were increased in p110beta-deficient myoblasts compared to oligomycin-stimulated control myoblasts when normalized to levels of total AMPK or ACC. Overall, these results suggest that p110beta positively regulates expression of AMPK in cultured myoblasts and in skeletal muscle in vivo; moreover, despite the reduced abundance of AMPK in p110beta-deficient myoblasts, loss of p110beta does not appear to impair AMPK activation following stimulus. These findings thus reveal a novel role for p110beta in mediating skeletal muscle metabolic signaling. |
