Chemerin/ChemR23 signaling axis is involved in the endothelial protection by KATP channel opener iptakalim  

作　　者：Rui-jun ZHAO Hai WANG 

机构地区：[1]Department of Environmental Medicine, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China [2]Thadweik Academy of Medicine, Beijing 100039, China

出　　处：《Acta Pharmacologica Sinica》2011年第5期573-580,共8页中国药理学报（英文版）

摘　　要：Aim： To elucidate the modulation of the chemerin/ChemR23 axis by iptakalim-induced opening of KATP channels and to determine the role of the chemerin/ChemR23 axis in the iptakalim-mediated endothelial protection. Methods： Cultured rat aortic endothelial cells （RAECs） were used. Chemerin secretion and ChemR23 protein expression were investigated using Western blot analysis. The gene expression level of ChemR23 was examined with RT-PCR. In addition, the release of nitric oxide （NO） was measured with a nitric oxide assay. Results： Homocysteine, uric acid, high glucose, or oxidized low-density lipoprotein （ox-LDL） down-regulated the chemerin secretion and ChemR23 gene/protein expression in RAECs as a function of concentration and time, which was reversed by pretreatment with iptaka- lim （1-10 pmol/L）. Moreover, these effects of iptakalim were abolished in the presence of the KATp channel antagonist glibenclamide （1 pmol/L）. Both iptakalim and recombinant chemerin restored the impaired NO production in RAECs induced by uric acid, and the effects were abolished by anti-ChemR23 antibodies. Conclusion： Iptakalim via opening KATp channels enhanced the endothelial chemerin/ChemR23 axis and NO production, thus improving endothelial function.Aim： To elucidate the modulation of the chemerin/ChemR23 axis by iptakalim-induced opening of KATP channels and to determine the role of the chemerin/ChemR23 axis in the iptakalim-mediated endothelial protection. Methods： Cultured rat aortic endothelial cells （RAECs） were used. Chemerin secretion and ChemR23 protein expression were investigated using Western blot analysis. The gene expression level of ChemR23 was examined with RT-PCR. In addition, the release of nitric oxide （NO） was measured with a nitric oxide assay. Results： Homocysteine, uric acid, high glucose, or oxidized low-density lipoprotein （ox-LDL） down-regulated the chemerin secretion and ChemR23 gene/protein expression in RAECs as a function of concentration and time, which was reversed by pretreatment with iptaka- lim （1-10 pmol/L）. Moreover, these effects of iptakalim were abolished in the presence of the KATp channel antagonist glibenclamide （1 pmol/L）. Both iptakalim and recombinant chemerin restored the impaired NO production in RAECs induced by uric acid, and the effects were abolished by anti-ChemR23 antibodies. Conclusion： Iptakalim via opening KATp channels enhanced the endothelial chemerin/ChemR23 axis and NO production, thus improving endothelial function.

关 键 词：ATP-sensitive potassium channel IPTAKALIM endothelial cells ChemR23 CHEMERIN NO 

分 类 号：Q424[生物学—神经生物学] Q25[生物学—生理学]