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• W2125877158 endingPage "663" @default.
• W2125877158 startingPage "654" @default.
• W2125877158 abstract "The endocannabinoid system (ECS) is activated at the onset of obesity and diverse metabolic diseases. Endocannabinoids mediate their physiological and behavioral effects by activating specific cannabinoid receptors, mainly cannabinoid receptor 1 (CB(1)R). Diabetic nephropathy (DN) is induced by hyperlipidemia, and renal proximal tubule cells are an important site for the onset of DN. However, the pathophysiology of CB(1)R, especially in the hyperlipidemia of DN, has not been elucidated. Therefore, we examined the effect of palmitic acid (PA) on CB(1)R expression and its related signal pathways in human renal proximal tubular cells (HK-2 cells). PA significantly increased CB(1)R mRNA and protein levels and induced CB(1)R internalization. PA-induced activation of CB(1)R is prevented by the treatment of AACOCF(3) (a cPLA(2) inhibitor), indomethacin and NS398 (a COX 2 inhibitors). Indeed, PA increased cPLA(2), and COX-2 but not COX-1. We also investigated whether the PA-induced activation of CB(1)R is linked to apoptosis. As a result, AM251 (a CB(1)R antagonist) attenuated PA-mediated apoptosis in a concentration-dependent manner. Furthermore, PA decreased GRP78 expression and induced increases in the endoplasmic reticulum (ER) stress signaling pathways p-PERK, p-eIF2α, p-ATF4, and CHOP, which were blocked by AM251 treatment. Moreover, PA increased the Bax/Bcl-2 ratio, cleaved PARP, and caspase-3 levels. The PA-induced apoptotic effects were decreased with CB(1)R-specific antagonist (AM251) treatment and CB1 si-RNA transfection. In conclusion, PA induced apoptosis through ER stress via CB(1)R expression in human proximal tubule cells. Our results provide evidence that CB(1)R blockade may be a potential anti-diabetic therapy for the treatment of DN." @default.
• W2125877158 created "2016-06-24" @default.
• W2125877158 creator A5023041420 @default.
• W2125877158 creator A5087339057 @default.
• W2125877158 creator A5088229898 @default.
• W2125877158 creator A5091280470 @default.
• W2125877158 date "2010-12-01" @default.
• W2125877158 modified "2023-10-13" @default.
• W2125877158 title "Cannabinoid receptor 1 mediates palmitic acid-induced apoptosis via endoplasmic reticulum stress in human renal proximal tubular cells" @default.
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