Citrate carrier (CiC), a mitochondrial membrane protein, plays an important metabolic role by transporting, in the form of citrate, acetyl-CoA from mitochondria into the cytosol for fatty acid and cholesterol synthesis. A PUFA (polyunsaturated fatty acids) response region, composed of a NF-Y site, an E-box like site, a SRE1 like site and four Sp1 sites, has been identified within the CiC promoter. Transcription factor SRE-Binding Protein-1 (SREBP-1c) is target for PUFA down-regulation of CiC transcription. Transfection and gel mobility shift assays indicated that a functional E-box like confers responsiveness to SREBP-1c. In H4IIE cells overexpression of SREBP-1c overrides arachidonic acid suppression but does not prevent the repression by docosahexaenoic acid. ChIP assay showed that docosahexaenoic acid affects the binding of NF-Y, Sp1 and SREBP-1 to PUFA response region whereas arachidonic acid alters only the binding of SREBP-1. PUFA inhibition of Cic gene transcription is mediated not only by the SREBP-1c but might also involve a reduction in Sp1 and NF-Y DNA binding, suggesting differential mechanisms in the Cic gene regulation by different PUFA.
n-3 and n-6 polyunsaturated fatty acids differently affect citrate carrier promoter activity.
DAMIANO, FABRIZIO;ALEMANNO, SIMONE;STANCA, ELEONORA;SICULELLA, Luisa;GNONI, Gabriele Vincenzo
2009-01-01
Abstract
Citrate carrier (CiC), a mitochondrial membrane protein, plays an important metabolic role by transporting, in the form of citrate, acetyl-CoA from mitochondria into the cytosol for fatty acid and cholesterol synthesis. A PUFA (polyunsaturated fatty acids) response region, composed of a NF-Y site, an E-box like site, a SRE1 like site and four Sp1 sites, has been identified within the CiC promoter. Transcription factor SRE-Binding Protein-1 (SREBP-1c) is target for PUFA down-regulation of CiC transcription. Transfection and gel mobility shift assays indicated that a functional E-box like confers responsiveness to SREBP-1c. In H4IIE cells overexpression of SREBP-1c overrides arachidonic acid suppression but does not prevent the repression by docosahexaenoic acid. ChIP assay showed that docosahexaenoic acid affects the binding of NF-Y, Sp1 and SREBP-1 to PUFA response region whereas arachidonic acid alters only the binding of SREBP-1. PUFA inhibition of Cic gene transcription is mediated not only by the SREBP-1c but might also involve a reduction in Sp1 and NF-Y DNA binding, suggesting differential mechanisms in the Cic gene regulation by different PUFA.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
