Medicinal Chemistry : Globular Adiponectin Inhibits Ethanol-Induced Reactive Oxygen Species Production through Modulation of NADPH Oxidase in Macrophages: Involvement of Liver Kinase B1/AMP-Activated Protein Kinase Pathwayⓢ = Medicinal Chemistry : Globular Adiponectin Inhibits Ethanol-Induced Reactive Oxygen Species Production through Modulation of NADPH Oxidase in Macrophages: Involvement of Liver Kinase B1/AMP-Activated Protein Kinase Pathwayⓢ

다국어 초록 (Multilingual Abstract)

Adiponectin,an adipokine predominantly secreted from adipo-cytes,has been shiwn to play protective roles against chronic alcohol consumption. Although escessive oxygen species(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 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 in both RAW 264.7 ,macrophages and primary murine peritoneal macrophages. Globular adiponectin also inhibited ethanol-induced activation df NADPH oxidase.In addition,gAcrp suppressed ethanol-induced increase in the expression of NADPH oxidase subunits,including Nox2 and P22phox,via modulation ofnuclear factor-kB pathway.Further-more,pretreatment with compound C,a selective inhibitor of AMPK,or knockdown of AMPK by small interfering PNA restored suppression of ethanol-induced ROS production and Nox2 espression by gAcrp. Finally,we found that gAcrp treatment induced phosphorylation of liver linase B1(LKB1),an upstream signaling molecule mediating AMPK actibation.Knockdown of LKB1 restored gAcrp-suppressed Nox2 expres-sion,suggesting that LKB1/AMPK pathway plays a critical role in the suppression of ethanol-induced ROS production and ctivation of NADPH oxidase by gAcrp. Taken together,these results demonstrate that globular adiponectin prevents ethanol-indyced 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.