Rui-jun Zhao1, Hai Wang. 1. Department of Environmental Medicine, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
Abstract
AIM: To elucidate the modulation of the chemerin/ChemR23 axis by iptakalim-induced opening of K(ATP) 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 iptakalim (1-10 μmol/L). Moreover, these effects of iptakalim were abolished in the presence of the K(ATP) channel antagonist glibenclamide (1 μmol/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 K(ATP) 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 K(ATP) 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 iptakalim (1-10 μmol/L). Moreover, these effects of iptakalim were abolished in the presence of the K(ATP) channel antagonist glibenclamide (1 μmol/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 K(ATP) channels enhanced the endothelial chemerin/ChemR23 axis and NO production, thus improving endothelial function.
Authors: Brian A Zabel; Takao Ohyama; Luis Zuniga; Ji-Yun Kim; Brent Johnston; Samantha J Allen; David G Guido; Tracy M Handel; Eugene C Butcher Journal: Exp Hematol Date: 2006-08 Impact factor: 3.084
Authors: Hidetada Yoshida; Jonathan E Feig; Alison Morrissey; Ioana A Ghiu; Michael Artman; William A Coetzee Journal: J Mol Cell Cardiol Date: 2004-10 Impact factor: 5.000
Authors: Maria Dona; Gabrielle Fredman; Jan M Schwab; Nan Chiang; Makoto Arita; Ahmad Goodarzi; Guiying Cheng; Ulrich H von Andrian; Charles N Serhan Journal: Blood Date: 2008-05-14 Impact factor: 22.113
Authors: Stephanie W Watts; Anne M Dorrance; Mark E Penfold; Jillian L Rourke; Christopher J Sinal; Bridget Seitz; Timothy J Sullivan; Trevor T Charvat; Janice M Thompson; Robert Burnett; Gregory D Fink Journal: Arterioscler Thromb Vasc Biol Date: 2013-04-04 Impact factor: 8.311
Authors: Jay Toulany; Sebastian D Parlee; Christopher J Sinal; Kathryn Slayter; Shelly McNeil; Kerry B Goralski Journal: Endocr Connect Date: 2016-11-08 Impact factor: 3.335
Authors: Christos G Kostopoulos; Sofia G Spiroglou; John N Varakis; Efstratios Apostolakis; Helen H Papadaki Journal: BMC Cardiovasc Disord Date: 2014-04-30 Impact factor: 2.298