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 language | English |
|---|---|
| Pages (from-to) | 203-209 |
| Number of pages | 7 |
| Journal | Journal of Applied Biomedicine |
| Volume | 12 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1 Nov 2014 |
Keywords
- Atherosclerosis
- ERK MAPK
- Indoxyl sulfate
- Macrophages
- Oxidized LDL