title: Fenofibrate, a PPARα agonist, protect proximal tubular cells from albumin-bound fatty acids induced apoptosis via the activation of NF-kB.
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.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University Shenyang 110001, People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zuo
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University Shenyang 110001, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of China Medical University Shenyang 110001, People's Republic of China.
authors.forename: Hanzhe
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Ophthalmology, The First Affiliated Hospital of China Medical University Shenyang 110001, People's Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Ma
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism / Q000633:toxicity*; D011345:Fenofibrate / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000378:metabolism / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation
chemical_list: C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D005227:Fatty Acids; D016209:Interleukin-8; D016328:NF-kappa B; D047493:PPAR alpha; D012710:Serum Albumin, Bovine; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D011345:Fenofibrate
keywords: Chronic kidney disease; apoptosis; fatty acids; fenofibrate; peroxisome proliferator-activated receptor α; proximal tubule epithelial cells