Disease relevance of Srebf2

• This study found that age-related renal matrix deposition and proteinuria were associated with increased renal expression of SREBP-1 and SREBP-2 and increased renal accumulation of triglyceride and cholesterol [1].
• These results suggested that hyperhomocysteinemia-induced activation of SREBP-2, CREB, and NF-Y was responsible for increased cholesterol biosynthesis by transcriptionally regulating HMG-CoA reductase expression in the liver leading to hepatic lipid accumulation and subsequently hypercholesterolemia [2].
• Homocysteine Thiolactone-Induced Hyperhomocysteinemia Does Not Alter Concentrations of Cholesterol and SREBP-2 Target Gene mRNAs in Rats [3].

High impact information on Srebf2

• Finally, the liver X receptor agonist T0901317 increased acetate incorporation and SREBP-1 but not SREBP-2 protein levels [4].
• In contrast, SREBP-2 was present in rat liver nuclei, and its target gene, HMG-CoA reductase, was expressed above adult levels prior to weaning [5].
• The negative effect of this site is abolished in obese rat adipocyte nuclei where SREBP2 is induced and can substitute for ADD1/SREBP1 binding to the inactive SRE [6].
• The activation of SREBP-2, CREB, and NF-Y preceded the increase in HMG-CoA reductase expression in Hcy-treated cells [2].
• Increase in hepatic expression of SREBP-2 by gemfibrozil administration to rats [7].

Biological context of Srebf2

• As for transcription factors for the CYP51 gene, enhanced gene expression of SREBP-2 was observed 6-12 h after LN treatment, whereas no enhanced gene expression of other SREBPs, SREBP-1a and SREBP-1c, was observed at any time after the treatment; for SREBP-1a, there was no significant change; for SREPB-1c, there was a drastic decrease [8].
• Furthermore, gene activation of SREBP-2, a gene activator of several cholesterogenic enzymes, occurred before the gene activations of FPPS, SQS and CYP51 [9].

Anatomical context of Srebf2

• In contrast, immunoreactive SREBP2, which was very low in nuclear extracts from lean rats, was induced in obese rat fat cells [6].
• Pretreatment of hepatocytes with inhibitors for transcription factors not only blocked the activation of SREBP-2, CREB, and NF-Y but also attenuated Hcy-induced HMG-CoA reductase mRNA expression [2].

Associations of Srebf2 with chemical compounds

• These data indicate that PUFA suppress the in vivo proteolytic release of SREBP-1 and -2, but the effect on SREBP-2 is transitory, possibly reflecting the ability of PUFA to enhance cholesterol losses via bile acid synthesis [10].
• These structural and functional changes were associated with significant decreases in renal nuclear SREBP-1 (5.2 in 24 m AL versus 3.3 densitometry units in 24 m CR; P < 0.01) and SREBP-2 (7.1 in 24 m AL versus 4.1 densitometry units in 24 m CR; P < 0.01) protein abundance and renal triglyceride and cholesterol contents [1].
• Atorvastatin and simvastatin enhanced not only HMG-CoA reductase but also the expression of the SREBP-2 gene itself [11].
• As a result of the overexpression of SREBP-2 caused by the statin treatment, genes regulated basically by SREBP-1, as FA synthase and acetyl-coenzyme A carboxylase, were also induced and their mRNA levels increased [11].
• An early increase in the transcriptional activity of SREBP-2 elicited by gemfibrozil administration might be responsible for the observed changes in HMG-CoA reductase, phosphatidate phosphohydrolase, and SREBP-2 expression [7].

Analytical, diagnostic and therapeutic context of Srebf2

• After the consumption of a second meal of fish oil, the nuclear level of mature SREBP-1 was only 16% of that in rats fed the fat-free diet, but the amount of nuclear SREBP-2 was not different from the level in rats fed the fat-free diet [10].
• The high expression of the key enzymes for fatty acid and cholesterol synthesis induced by immobilization was not paralleled by an increase of the hepatic sterol-regulatory element binding protein (SREBP)-1 and SREBP-2 mRNA content [12].

References