RT Journal Article
SR Electronic
T1 Globular Adiponectin Inhibits Ethanol-Induced ROS Production through Modulation of NADPH Oxidase in Macrophages: Involvement of LKB1/AMPK pathway
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.114.093039
DO 10.1124/mol.114.093039
A1 Mi Jin Kim
A1 Laura E Nagy
A1 Pil-Hoon Park
YR 2014
UL http://molpharm.aspetjournals.org/content/early/2014/05/20/mol.114.093039.abstract
AB Adiponectin, an adipokine predominantly secreted from adipocytes, has been shown to play protective roles against chronic alcohol consumption. While excessive ROS production in macrophages is considered one of the critical events for ethanol-induced damage in various target tissues, the effect of adiponectin on ethanol-induced ROS production is not clearly understood. In the present study, we investigated the effect of globular adiponectin (gAcrp) on ethanol-induced ROS production and the potential mechanisms underlying these effects of gAcrp in macrophages. Here, we demonstrated that gAcrp prevented ethanol-induced ROS production both in RAW 264.7 macrophages and primary murine peritoneal macrophages. Globular adiponectin also inhibited ethanol-induced activation of NADPH oxidase. In addition, gAcrp suppressed ethanol-induced increase in expression of NADPH oxidase subunits, including Nox2 and p22phox, via modulation of NF-κB pathway. Furthermore, pretreatment with Compound C, a selective inhibitor of AMPK, or knockdown of AMPK by small interfering RNA (siRNA) restored suppression of ethanol-induced ROS production and Nox2 expression by gAcrp. Finally, we found that gAcrp treatment induced phosphorylation of liver kinase B1 (LKB1), an upstream signaling molecule mediating AMPK activation. Knockdown of LKB1 restored gAcrp-suppressed Nox2 expression, suggesting that LKB1/AMPK pathway plays a critical role in the suppression of ethanol-induced ROS production and activation of NADPH oxidase by gAcrp. Taken together, these results demonstrate that globular adiponectin prevents ethanol-induced ROS production, at least in part, via modulation of NADPH oxidase in macrophages. Further, LKB1/AMPK axis plays an important role in the suppression of ethanol-induced NADPH oxidase activation by gAcrp in macrophages.