1: J Lipid Res. 2007 Jul;48(7):1628-36. Epub 2007 Apr 23.

SREBP-1 regulates the expression of heme oxygenase 1 and the
phosphatidylinositol-3 kinase regulatory subunit p55 gamma.

Kallin A, Johannessen LE, Cani PD, Marbehant CY, Essaghir A, Foufelle F, Ferré P,
Heldin CH, Delzenne NM, Demoulin JB.

Université catholique de Louvain, Christian de Duve Institute of Cellular
Pathology, Experimental Medicine Unit, Brussels, Belgium.

Sterol-regulatory element binding proteins (SREBPs) control the expression of
genes involved in fatty acid and cholesterol biosynthesis. Using microarrays, we 
observed that mature SREBP-1 also induced the expression of genes unrelated to
lipid metabolism, such as heme oxygenase 1 (HMOX1), plasma glutathione
peroxidase, the phosphatidylinositol-3 kinase regulatory subunit p55 gamma,
synaptic vesicle glycoprotein 2A, and COTE1. The expression of these genes was
repressed upon addition of sterols, which block endogenous SREBP cleavage, and
was induced by the statin drug mevinolin. Stimulation of fibroblasts with
platelet-derived growth factor, which activates SREBP-1, had a similar effect.
Fasted mice that were refed with a high-carbohydrate diet presented an increased 
expression of HMOX1 and p55 gamma in the liver. Overall, the transcriptional
signature of SREBP-1 in fibroblasts stimulated by growth factors was very similar
to that described in liver cells. We analyzed the HMOX1 promoter and found one
SREBP binding site of the E-box type, which was required for regulation by
SREBP-1a and SREBP-1c but was insensitive to SREBP-2. In conclusion, our data
suggest that SREBP-1 regulates the expression of stress response and signaling
genes, which could contribute to the metabolic response to insulin and growth
factors in various tissues.

PMID: 17452746 [PubMed - indexed for MEDLINE]

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