Disease relevance of Scarb1

• Factors associated with cholestasis appear to be involved in transcriptional control of intestinal SR-BI expression [1].
• Down-regulation of hepatic high-density lipoprotein receptor, SR-B1, in nephrotic syndrome [2].
• Hepatic HDL receptor, SR-B1 and Apo A-I expression in chronic renal failure [3].
• The PM toxicity metrics evaluated were inhibition of cell proliferation (SRB and Janus green) and inhibition of cellular metabolism (MTT) [4].

High impact information on Scarb1

• Scavenger receptor class B type I (SR-BI) is a high-density lipoprotein (HDL) receptor that mediates the selective uptake of HDL cholesterol and cholesterol secretion into bile in the liver [5].
• Regulation of SR-BI protein levels by phosphorylation of its associated protein, PDZK1 [5].
• Administration of glucagon to Wistar rats increased PDZK1 phosphorylation as well as hepatic SR-BI and PDZK1 expression while it decreased plasma HDL levels, indicating that PDZK1 phosphorylation is hormonally regulated [5].
• Moreover, phagocytosis of spermatogenic cells by Sertoli cells was inhibited in the presence of an anti-SR-BI antibody [6].
• Overexpression of the rat SR-BI cDNA increased the PS-mediated phagocytic activity of Sertoli cell-derived cell lines [6].

Biological context of Scarb1

• The class-B type-I scavenger receptor (SR-BI) plays a key role in cholesterol homeostasis; it mediates the selective uptake of lipoprotein cholesterol to steroidogenic tissues [7].
• SR-BI gene expression was high in steroid-producing tissues and in the liver, consistent with a role of this receptor in the uptake of HDL cholesterol [8].
• The results of these studies demonstrate that the rat HDL receptor SR-BI promoter contains two sterol response elements (pSRE and dSRE) through which SREBP-1a can bind and activate transcription of this gene [9].
• The rat and human SR-BI genes were mapped to a region previously linked between rat and human chromosomes 12 [8].
• The chromosomal locations of the rat and human SR-BI homologs suggest that this gene is a new member of a previously reported, conserved synteny group [8].

Anatomical context of Scarb1

• Thus, induction of the SR-BI receptor system and induction of the HDL-selective cholesterol uptake pathway in rat granulosa cells appear to be linked morphologically, biochemically, and functionally [10].
• SR-BI gene expression was detected in several rat tissues, with high levels in ovarian tissue, liver, and adrenal cortex, as determined by ribonuclease protection assay and in situ hybridization [8].
• SR-BI was also observed in the cytoplasm of smooth muscle cells [11].
• Immunoblotting analysis indicated that SR-BI was expressed in the cell membrane [11].
• The results showed that SR-BI was specifically localized on the surface of the endothelial cells and smooth muscle cells [11].

Associations of Scarb1 with chemical compounds

• Differential regulation of steroid hormone biosynthesis in R2C and MA-10 Leydig tumor cells: role of SR-B1-mediated selective cholesteryl ester transport [12].
• Furthermore the expression of SR-BI mRNA in the ovary is stimulated by LH and cyclic AMP (cAMP) [13].
• Class B scavenger receptor type I (SR-BI), a candidate for the PS receptor, was detected in Sertoli cells [6].
• The treatment of theca-interstitial cells with anti-SR-BI antibody blocked more than 90% of HDL plus human chorionic gonadotropin-stimulated androstenedione production, and selective HDL-CE uptake [14].
• Sterol regulatory element-binding protein-1a binds to cis elements in the promoter of the rat high density lipoprotein receptor SR-BI gene [9].

Other interactions of Scarb1

• Expression of SR-BI receptor and StAR protein in rat ocular tissues [7].
• The cysteine protease inhibitor N-acetyl-leucyl-leucyl-norleucinal, which inhibits SREBP degradation, enhanced the effect of SREBP-1a on the regulation of the rat HDL receptor SR-BI gene [9].
• Consistent with this fact, we have recently shown that steroidogenic factor-1 (SF-1) mediates cAMP activation of the HDL receptor SR-BI gene [9].
• Once lactation began, reductase, cholesterol acyltransferase, 7alpha-hydroxylase activities, low density lipoprotein receptors, and mdr2 increased while SR-B1 decreased [15].
• Uptake of N-Rh-PE from liposomes containing phosphatidylserine was higher than [(3)H]COE, and was further enhanced by apolipoprotein A-I, confirming involvement of SR-BI in the selective uptake of liposomal N-Rh-PE by cells [16].

Analytical, diagnostic and therapeutic context of Scarb1

• We show by RT-PCR, western blot, in situ hybridization and immunohistochemistry analysis that SR-BI is highly expressed in different neuro-retinal and non-neuronal cells types on rat eye [7].
• Immunohistochemistry of the steroidogenic acute regulatory protein (StAR) involved in neurosteroid production showed the same expression pattern than SR-BI in rat eye [7].
• Consistent with the possibility that SREBP-1a may be involved in the regulation of the HDL receptor SR-BI gene, we found that mature SREBP-1a levels increased up to 11-fold in the ovary after treatment with 50 U hCG [9].
• To determine whether SREBP-1a could directly regulate the expression of the rat HDL receptor SR-BI gene, approximately 2.2 kb of the receptor SR-BI promoter were cloned and sequenced, and deletion analysis and mobility shift assays were performed [9].
• In this study, we used immunoelectron microscopy to investigate the subcellular localization of scavenger receptor class B type I (SR-BI) in the arterial walls of rats [11].

References