title: [Activation of SUR2B/Kir6.1-type K(ATP) channels protects glomerular endothelial, mesangial and tubular epithelial cells against oleic acid renal damage].
abstract: Cumulative evidence suggests that renal vascular endothelial injury play an important role in initiating and extending tubular epithelial injury and contribute to the development of ischemic acute renal failure. Our previous studies have demonstrated that iptakalim's endothelium protection is related to activation of SUR2B/Kir6.1 subtype of ATP sensitive potassium channel (K(ATP)) in the endothelium. It has been reported that SUR2B/Kir6.1 channels are widely distributed in the tubular epithelium, glomerular mesangium, and the endothelium and the smooth muscle of blood vessels. Herein, we hypothesized that activating renal K(ATP) channels with iptakalim might have directly neroprotective effects. In this study, glomerular endothelial, mesangial and tubular epithelial cells which are the main cell types to form nephron were exposed to oleic acid (OA) at various concentrations for 24 h. 0.25 microl/ml OA could cause cellular damage of glomerular endothelium and mesangium, while 1.25 microl/ml OA could lead to the injury of three types of renal cells. It was observed that pretreatment with iptakalim at concentrations of 0.1, 1, 10 or 100 micromol/L prevented cellular damage of glomerular endothelium and tubular epithelium, whereas iptakalim from 1 to 100 micromol/L prevented the injury of mesangial cells. Our data showed iptakalim significantly increased survived cell rates in a concentration-dependent manner, significantly antagonized by glibenclamide, a K(ATP) blocker. Iptakalim played a protective role in the main cell types of kidney, which was consistent with natakalim, a highly selective SUR2B/Kir6.1 channel opener. Iptakalim exerted protective effects through activating SUR2B/Kir6.1 channels, suggesting a new strategy for renal injury by its endothelial and renal cell protection.
authors.affiliation: Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D005905:Glyburide / Q000009:adverse effects; D006801:Humans; D054086:KATP Channels / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism; D019301:Oleic Acid / Q000009:adverse effects*; D011437:Propylamines / Q000494:pharmacology*; D020011:Protective Agents / Q000494:pharmacology
chemical_list: D054086:KATP Channels; C502260:N-(1-methylethyl)-1,1,2-trimethylpropylamine; D011437:Propylamines; D020011:Protective Agents; C092520:uK-ATP-1 potassium channel; D019301:Oleic Acid; D005905:Glyburide