PPARα Contributes to Tubular Protection

[摘要] Peroxisome proliferator–activated receptors (PPAR) are ligand-inducible transcription factors that belong to the nuclear receptor family. They include three major subtypes: PPARα, PPARβ/δ, and PPARγ. Initially, PPARα was identified as the molecular target for the hypolipidemic fibrate drugs that induce peroxisome proliferation in rodents, which explains its name. Further studies have demonstrated that PPAR also bind endogenous ligands such as fatty acids and fatty acid derivatives provided by the lipoxygenase and cyclooxygenase pathways, PPARα being a particular target for polyunsaturated fatty acids such as linoleic acid, dodecahexanoic acid, and eicosapentaenoic acid. After activation by their ligands, PPAR form heterodimers with the retinoic receptor RXR and interact with peroxisome proliferator response element present in the promoter of their target genes. By this transcriptional mechanism, PPARα increases the activity of enzymes that are involved in fatty acid β-oxidation, lowering triglyceride levels in vivo. Thus, it would not be surprising if PPARα is expressed in tissues involved in fatty acid oxidation, including liver, kidney, heart, skeletal muscle, and brown fat. Within the kidney, PPARα is predominantly present in proximal tubules and medullary thick ascending limbs.1

[学科分类] 泌尿医学

[关键词] Bone marrow necrosis;Sickle cell disease;Hyperhemolysis syndrome