Fenofibrate, a PPARα agonist, protect proximal tubular cells from albumin-bound fatty acids induced apoptosis via the activation of NF-kB

PPARα 激动剂非诺贝特通过激活 NF-kB 保护近端肾小管细胞免受白蛋白结合脂肪酸诱导的细胞凋亡

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作者:Nan Zuo, Xiaoyu Zheng, Hanzhe Liu, Xiaoli Ma

Abstract

Albumin-bound fatty acids is the main cause of renal damage, PPARα is responsible in the metabolism of fatty acids. Previous study found that PPARα played a protective role in fatty acids overload associated tubular injury. The aim of the present study is to investigate whether fenofibrate, a PPARα ligands, could contribute to the renoprotective action in fatty acids overload proximal tubule epithelial cells. We observed in HK-2 cells that fenofibrate significantly inhibited fatty acids bound albumin (FA-BSA) induced up-regulation of MCP-1 and IL-8. Treatment with fenofibrate attenuated renal oxidative stress induced by FA-BSA as evidenced by decreased MDA level, increased SOD activity and catalase, GPx-1 expression. FA-BSA induced apoptosis of HK-2 cells were also obviously prevented by fenofibrate. Furthermore, fenofibrate significantly increased the expression of PPARα mRNA and protein in FA-BSA treated cells. Finally, the activation of NF-kB induced by FA-BSA was markedly suppressed by fenofibrate. Taken together, our study describes a renoprotective role of fenofibrate in fatty acids associated tubular toxicity, and the transcriptional activation of PPARα and suppression of NF-kB were at least partially involved.

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