Statins, fibrates and retinoic acid upregulate mitochondrial acylcarnitine carrier gene expression

In this study, we investigated the effects of statins, fibrates, 9-cis-retinoic acid and forskolin on the transcription of the mitochondrial carnitine/acylcarnitine carrier (CAC) gene. Statins, fibrates, retinoic acid and forskolin activate luciferase gene reporter activity driven by the −334/+3 bp...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2009-10, Vol.388 (4), p.643-647
Main Authors: Iacobazzi, Vito, Convertini, Paolo, Infantino, Vittoria, Scarcia, Pasquale, Todisco, Simona, Palmieri, Ferdinando
Format: Article
Language:English
Subjects:
9-Cis-retinoic acid
Animals
Anticholesteremic Agents - pharmacology
CAC deficiency
Carnitine - analogs & derivatives
Carnitine - pharmacology
Carnitine/acylcarnitine carrier
Clofibric Acid - pharmacology
Colforsin - pharmacology
Fatty acid β-oxidation
Fibrates
Forskolin
Gene expression
Gene Expression - drug effects
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Membrane Transport Proteins - genetics
Mitochondria
Mitochondria - metabolism
PPAR alpha - metabolism
PPRE
Promoter Regions, Genetic - drug effects
Rats
Statins
Tretinoin - pharmacology
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Summary:In this study, we investigated the effects of statins, fibrates, 9-cis-retinoic acid and forskolin on the transcription of the mitochondrial carnitine/acylcarnitine carrier (CAC) gene. Statins, fibrates, retinoic acid and forskolin activate luciferase gene reporter activity driven by the −334/+3 bp region of the human CAC promoter containing wild-type (but not mutated) PPRE. These four agents also increase CAC transcript and protein levels. The combinations of statins and fibrates, retinoic acid and fibrates and fibrates and forskolin act synergistically. Mevalonate abolishes the activation of CAC gene expression by statins; the inhibitor of the PKA pathway H89 suppresses the stimulation of CAC gene expression by forskolin. Because CAC is essential for fatty acid β-oxidation, the above results on the regulation of CAC gene expression provide a novel contribution to the understanding of the hypolipidemic action of statins, fibrates and retinoic acid.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2009.08.008