| First Author | Shi T | Year | 2016 |
| Journal | J Recept Signal Transduct Res | Volume | 36 |
| Issue | 3 | Pages | 261-70 |
| PubMed ID | 26832303 | Mgi Jnum | J:319151 |
| Mgi Id | MGI:6862926 | Doi | 10.3109/10799893.2015.1091475 |
| Citation | Shi T, et al. (2016) alpha1A-Adrenergic receptor prevents cardiac ischemic damage through PKCdelta/GLUT1/4-mediated glucose uptake. J Recept Signal Transduct Res 36(3):261-70 |
| abstractText | While alpha(1)-adrenergic receptors (ARs) have been previously shown to limit ischemic cardiac damage, the mechanisms remain unclear. Most previous studies utilized low oxygen conditions in addition to ischemic buffers with glucose deficiencies, but we discovered profound differences if the two conditions are separated. We assessed both mouse neonatal and adult myocytes and HL-1 cells in a series of assays assessing ischemic damage under hypoxic or low glucose conditions. We found that alpha(1)-AR stimulation protected against increased lactate dehydrogenase release or Annexin V(+) apoptosis under conditions that were due to low glucose concentration not to hypoxia. The alpha(1)-AR antagonist prazosin or nonselective protein kinase C (PKC) inhibitors blocked the protective effect. alpha(1)-AR stimulation increased (3)H-deoxyglucose uptake that was blocked with either an inhibitor to glucose transporter 1 or 4 (GLUT1 or GLUT4) or small interfering RNA (siRNA) against PKCdelta. GLUT1/4 inhibition also blocked alpha(1)-AR-mediated protection from apoptosis. The PKC inhibitor rottlerin or siRNA against PKCdelta blocked alpha(1)-AR stimulated GLUT1 or GLUT4 plasma membrane translocation. alpha(1)-AR stimulation increased plasma membrane concentration of either GLUT1 or GLUT4 in a time-dependent fashion. Transgenic mice overexpressing the alpha(1A)-AR but not alpha(1B)-AR mice displayed increased glucose uptake and increased GLUT1 and GLUT4 plasma membrane translocation in the adult heart while alpha(1A)-AR but not alpha(1B)-AR knockout mice displayed lowered glucose uptake and GLUT translocation. Our results suggest that alpha(1)-AR activation is anti-apoptotic and protective during cardiac ischemia due to glucose deprivation and not hypoxia by enhancing glucose uptake into the heart via PKCdelta-mediated GLUT translocation that may be specific to the alpha(1A)-AR subtype. |
