Effects of fatty acids on mitochondrial beta-oxidation enzyme gene expression in renal cell lines.
Regulatory effects of fatty acids on gene expression of medium-chain acyl-CoA dehydrogenase (MCAD), a mitochondrial beta-oxidation enzyme, were investigated in rabbit kidney cell lines derived from proximal tubule (RC.SV1), thick ascending limb of Henle's loop (RC.SV2), or collecting duct (RC.SV3). Exposure to long-chain fatty acids led to significant increases (2-fold) in MCAD mRNA abundance in RC.SV1 and RC.SV2 cells; kinetics and dose-response studies established that maximal MCAD gene stimulation was reached 4 h after addition of 50 microM oleate (C18:1) in the culture medium. These effects of fatty acids were totally abolished in the presence of 1 microg/ml actinomycin D, a transcription inhibitor. Staining of cellular lipids revealed that fatty acid-induced gene stimulation could occur in the absence of cellular fatty acid accumulation. Altogether, these data indicate that small changes in cellular fatty acid flux can have direct short-term effects on fatty acid oxidation enzyme gene expression in renal cells, and this might take part in the regulation of cellular fatty acid homeostasis in response to changes in tubular fluid composition.
Institut National de la Santé et de la Recherche Médicale U319, Université Paris VII, 75015 Paris, France.
Fetta
F
Ouali
Fatima
F
Djouadi
Jean
J
Bastin
D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002210:Caprylates / Q000378:metabolism / Q000494:pharmacology; D002461:Cell Line, Transformed; D002994:Clofibrate / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007684:Kidney Tubules / Q000166:cytology / Q000201:enzymology*; D007848:Laurates / Q000378:metabolism / Q000494:pharmacology; D050356:Lipid Metabolism; D008928:Mitochondria / Q000201:enzymology*; D019301:Oleic Acid / Q000378:metabolism / Q000494:pharmacology; D010168:Palmitates / Q000378:metabolism / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D014157:Transcription Factors / Q000037:antagonists & inhibitors
D002210:Caprylates; D005227:Fatty Acids; D000960:Hypolipidemic Agents; D007848:Laurates; D010168:Palmitates; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D003609:Dactinomycin; D019301:Oleic Acid; D042964:Acyl-CoA Dehydrogenase; D044942:Acyl-CoA Dehydrogenase, Long-Chain; D002994:Clofibrate