| First Author | Zhang Y | Year | 2013 |
| Journal | Am J Physiol Endocrinol Metab | Volume | 305 |
| Issue | 12 | Pages | E1436-43 |
| PubMed ID | 24129398 | Mgi Jnum | J:206062 |
| Mgi Id | MGI:5547850 | Doi | 10.1152/ajpendo.00445.2013 |
| Citation | Zhang Y, et al. (2013) Adiponectin inhibits oxidative/nitrative stress during myocardial ischemia and reperfusion via PKA signaling. Am J Physiol Endocrinol Metab 305(12):E1436-43 |
| abstractText | The cardioprotective effects of adiponectin (APN) against myocardial ischemia/reperfusion (MI/R) injury are well known. However, comprehension of the mechanisms mediating intracellular APN signaling remains incomplete. We recently demonstrate the antioxidant/antinitrative effects of APN are not dependent on AMPK. Protein kinase A (PKA) has been previously shown to be activated by APN, with uncertain relevance to APN cardiac protection. The current study determined whether the antioxidative/antinitrative effect of APN is mediated by PKA. Administration of APN (2 mug/g) 10 min before reperfusion significantly enhanced cardiac PKA activity, reduced oxidative stress, and decreased infarct size. Knockdown of cardiac PKA expression (PKA-KD) by intramyocardial injection of PKA-siRNAs (>70% suppression) significantly inhibited APN cardioprotection determined by cardiac apoptosis, infarct size, and cardiac function. Moreover, PKA-KD virtually abolished the suppressive effect of APN on MI/R-induced NADPH oxidase overexpression and superoxide overproduction and partially inhibited the effect of APN on nitrative protein modification in MI/R heart. Mechanistically, APN significantly inhibited MI/R-induced IKK/IkappaB phosphorylation and NF-kappaB activation, which were blocked in PKA-KD heart. Finally, the PKA-mediated antioxidant/antinitrative and cardioprotective effects of APN are intact in AMPK-deficient mice, suggesting that there is no cross talk between AMPK and PKA signaling in APN cardioprotection. Collectively, we demonstrate for the first time that APN inhibits oxidative/nitrative stress during MI/R via PKA-dependent NF-kappaB inhibition. |
