Indoxyl sulfate stimulates oxidized LDL uptake through up-regulation of CD36 expression in THP-1 macrophages

Indoxyl sulfate (is),a uremic toxin,is considered as a risk factor for accelerated athero-sclerosis in patients with chronic kidney disease. as uptake of oxidized low-density lipoprotein (ox-ldl) in macrophages is a key event in the progression of atherosclerosis,the aim of this study was to determine direct effects of is on uptake of ox-ldl in macrophages. flow cytometric analysis revealed that is significantly stimulated ox-ldl uptake by thp-1 macrophages in both dose-and time-dependent manners. a cd36 inhibitor,sulfosuccinimidyl oleate (sso),and erk1/2 inhibitors,pd98059 and u0126,could suppress the is-stimulated ox-ldl uptake. is also stimulated cd36 expression,which was inhibited by pd98059 and u0126. western blotting analysis showed that is significantly activated erk1/2 mitogen-activated protein kinase (mapk) pathway by increasing its phosphorylation level. further,cck-8 assay showed that is exerted its effects without affecting cell viability. in conclusion,is stimulated ox-ldl uptake through up-regulation of cd36 expression in thp-1 macrophages,partly via erk1/2 mapk pathway. this might be one of the mechanisms underlying the progression of atherosclerosis in patients with chronic kidney disease. © 2014 faculty of health and social studies,university of south bohemia in ceske budejovice. published by elsevier urban & partner sp. z o.o. all rights reserved.