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

Longxing Cao, Qiang Fu, Bing Hui Wang, Wen Jin, Zhiliang Li

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)203-209
Number of pages7
JournalJournal of Applied Biomedicine
Volume12
Issue number4
DOIs
Publication statusPublished - 1 Nov 2014

Keywords

  • Atherosclerosis
  • ERK MAPK
  • Indoxyl sulfate
  • Macrophages
  • Oxidized LDL

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