Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.99.3 (acyl-CoA dehydrogenase)
 1,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Effects of fatty acids on mitochondrial beta-oxidation enzyme gene expression in renal cell lines. 1211 May 17

Previous studies demonstrated that during cisplatin-induced acute renal failure, there is a significant reduction in proximal tubule fatty acid oxidation. We now report on the effects of peroxisome proliferator-activated receptor-alpha (PPAR alpha) ligand Wy-14643 (WY) on the abnormalities of medium chain fatty acid oxidation and pyruvate dehydrogenase complex (PDC) activity in kidney tissue of cisplatin-treated mice. Cisplatin causes a significant reduction in mRNA levels and enzyme activity of mitochondrial medium chain acyl-CoA dehydrogenase (MCAD). PPAR alpha ligand WY ameliorated cisplatin-induced acute renal failure and prevented cisplatin-induced reduction of mRNA levels and enzyme activity of MCAD. In contrast, in cisplatin-treated PPAR alpha null mice, WY did not protect kidney function and did not reverse cisplatin-induced decreased expression of MCAD. Cisplatin inhibited renal PDC activity before the development of acute tubular necrosis, and PDC inhibition was reversed by pretreatment with PPAR alpha agonist WY. Cisplatin also induced increased mRNA and protein levels of pyruvate dehydrogenase kinase-4 (PDK4), and PPAR alpha ligand WY prevented cisplatin-induced increased expression of PDK4 protein levels in wild-type mice. We conclude that PPAR alpha agonists have therapeutic potential for cisplatin-induced acute renal failure. Use of PPAR alpha ligands prevents acute tubular necrosis by ameliorating cisplatin-induced inhibition of two distinct metabolic processes, MCAD-mediated fatty acid oxidation and PDC activity.
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PMID:PPAR alpha ligand protects during cisplatin-induced acute renal failure by preventing inhibition of renal FAO and PDC activity. 1461 80