Adiponectin inhibits oxidative/nitrative stress during myocardial ischemia and reperfusion via PKA signaling.
Publication/Presentation Date
12-1-2013
Abstract
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 μg/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/IκB phosphorylation and NF-κB 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-κB inhibition.
Volume
305
Issue
12
First Page
1436
Last Page
1443
ISSN
1522-1555
Published In/Presented At
Zhang, Y., Wang, X. L., Zhao, J., Wang, Y. J., Lau, W. B., Yuan, Y. X., Gao, E. H., Koch, W. J., & Ma, X. L. (2013). Adiponectin inhibits oxidative/nitrative stress during myocardial ischemia and reperfusion via PKA signaling. American journal of physiology. Endocrinology and metabolism, 305(12), E1436–E1443. https://doi.org/10.1152/ajpendo.00445.2013
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
24129398
Department(s)
Administration and Leadership
Document Type
Article