کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2087710 | 1080684 | 2014 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Indoxyl sulfate stimulates oxidized LDL uptake through up-regulation of CD36 expression in THP-1 macrophages Indoxyl sulfate stimulates oxidized LDL uptake through up-regulation of CD36 expression in THP-1 macrophages](/preview/png/2087710.png)
• Indoxyl sulfate (IS), a uremic toxin, stimulates Ox-LDL uptake in THP-1 macrophages via CD36.
• IS increases CD36 expression in THP-1 macrophages via ERK1/2 pathway.
• IS activates ERK1/2 pathway in THP-1 macrophages.
• IS may contribute to progression of atherosclerosis in patients with chronic kidney disease.
Indoxyl sulfate (IS), a uremic toxin, is considered as a risk factor for accelerated atherosclerosis 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.
Journal: Journal of Applied Biomedicine - Volume 12, Issue 4, November 2014, Pages 203–209