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Gene Review

Scarb1  -  scavenger receptor class B, member 1

Mus musculus

Synonyms: AI120173, CD36, Cd36l1, Cla-1, Cla1, ...
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Disease relevance of Scarb1


Psychiatry related information on Scarb1

  • CONCLUSIONS: A genetic variant at the SR-BI gene promoter region might explain a significant proportion of individual differences in HDL-C levels among Taiwanese Chinese. Our results require further replication in an independent population [8].

High impact information on Scarb1


Chemical compound and disease context of Scarb1


Biological context of Scarb1

  • We now show up-regulation of adrenal SR-BI mRNA and protein in apoA-I0 mice, but not in apoA-II0, LDL receptor 0, apoE0, or cholesteryl ester transfer protein transgenic mice [15].
  • SR-BI-apoE interactions may contribute to cholesterol homeostasis in tissues and cells expressing SR-BI that are accessible to apoE-containing lipoproteins [16].
  • In the present investigation we report that ciprofibrate treatment causes the down-regulation of hepatic scavenger receptor class B, type I (SR-BI) protein expression in the livers of apoE-deficient mice [3].
  • After a meal containing [(14)C]cholesterol and [(3)H]triolein, SR-BI transgenic mice presented a rise in intestinal absorption of both lipids that was not due to a defect in chylomicron clearance nor to a change in the bile flow or the bile acid content [17].
  • We have generated transgenic mice overexpressing SR-BI primarily in the intestine by using the mouse SR-BI gene under the control of intestinal specific "apoC-III enhancer coupled with apoA-IV promoter." We found SR-BI overexpression with respect to the natural protein along the intestine and at the top of the villosities [17].

Anatomical context of Scarb1

  • SR-BI mediates HDL cholesteryl ester uptake in a process in which HDL lipids are selectively transferred to the cell membrane without the uptake and degradation of the HDL particle [18].
  • Binding was nearly abolished in a cell line expressing the ldlA (Q402R/Q418R) double mutant form of SR-BI that is unable to bind native high density lipoprotein but binds low density lipoprotein normally [16].
  • Scavenger receptor BI (SR-BI), a putative high density lipoprotein (HDL) receptor, mediates the selective uptake of HDL cholesteryl ester into cells and is highly expressed in adrenal gland (Acton, S., Rigotti, A., Landschulz, K.T., Xu, S., Hobbs, H.H., and Krieger, M. (1996) Science 271, 518-520) [15].
  • Thus, mSR-BI colocalizes with caveolae, and this raises the possibility that the unique properties of these specialized cell surface domains may play a critical role in SR-BI-mediated transfer of lipids between lipoproteins and cells [19].
  • We also report that remnants isolated from the plasma of ciprofibrate-treated apoE-deficient mice bind to murine SR-BI expressed in stably transfected cultured cells [3].

Associations of Scarb1 with chemical compounds


Physical interactions of Scarb1

  • RECENT FINDINGS: The PDZ domain-containing adaptor protein PDZK1 has been shown to bind to and control the activity of the high-density lipoprotein receptor SR-BI via a tissue-specific posttranscriptional mechanism [24].
  • Conversely, loading macrophages with cholesterol or cholesteryl ester (acetate) with MebetaCD:cholesterol complexes increased CD36 mRNA, 125I-labeled OxLDL binding, and CD36 surface expression as determined by fluorescence activated cell sorting [25].

Regulatory relationships of Scarb1

  • This troglitazone-induced increase in the expression of aP2 and FAT/CD36 was markedly enhanced in the liver in ob/ob mice [20].
  • CONCLUSIONS: The increased hepatic CE levels, following P-407 treatment, was neither related to an up-regulation of ACAT2 nor enhanced SR-BI expression [26].
  • Furthermore, selective elimination of SR-BI expression in bone marrow-derived cells resulted in increased diet-induced atherosclerosis in LDL receptor knockout mice without concomitant alterations in the distributions of plasma lipoprotein cholesterol [27].
  • Low-density lipoprotein from apolipoprotein E-deficient mice induces macrophage lipid accumulation in a CD36 and scavenger receptor class A-dependent manner [28].
  • These findings indicate that SR-BI expression may be influenced by changes in HL activity [29].

Other interactions of Scarb1

  • Overexpression of SR-BI by adenoviral vector reverses the fibrateinduced hypercholesterolemia of apolipoprotein E-deficient mice [3].
  • The action of hepatic lipase on apoA-I-containing lipoproteins may facilitate the SR-BI-mediated uptake of HDL lipid [15].
  • Upon short-term (2 days) treatment with leptin, a dose-dependent increase was seen in the SR-BI protein and mRNA, whereas the Cyp7a1 protein and mRNA were reduced [30].
  • In contrast to the liver, troglitazone did not increase the expression of aP2, FAT/CD36, and uncoupling protein-2 in adipose tissue in lean or ob/ob mice [20].
  • It also suppressed expression of the 2 major scavenger receptors (scavenger receptor-A [SR-A] and CD36), in part by inhibiting IL-6, and inhibited macrophage foam cell formation [31].

Analytical, diagnostic and therapeutic context of Scarb1


  1. Scavenger Receptor BI Protects against Septic Death through Its Role in Modulating Inflammatory Response. Guo, L., Song, Z., Li, M., Wu, Q., Wang, D., Feng, H., Bernard, P., Daugherty, A., Huang, B., Li, X.A. J. Biol. Chem. (2009) [Pubmed]
  2. Scavenger receptor BI prevents nitric oxide-induced cytotoxicity and endotoxin-induced death. Li, X.A., Guo, L., Asmis, R., Nikolova-Karakashian, M., Smart, E.J. Circ. Res. (2006) [Pubmed]
  3. Overexpression of SR-BI by adenoviral vector reverses the fibrateinduced hypercholesterolemia of apolipoprotein E-deficient mice. Fu, T., Kozarsky, K.F., Borensztajn, J. J. Biol. Chem. (2003) [Pubmed]
  4. Sepsis syndrome stimulates proximal tubule cholesterol synthesis and suppresses the SR-B1 cholesterol transporter. Zager, R.A., Johnson, A.C., Hanson, S.Y. Kidney Int. (2003) [Pubmed]
  5. Scavenger receptor class B type I in high-density lipoprotein metabolism, atherosclerosis and heart disease: lessons from gene-targeted mice. Trigatti, B., Covey, S., Rizvi, A. Biochem. Soc. Trans. (2004) [Pubmed]
  6. Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice. Febbraio, M., Podrez, E.A., Smith, J.D., Hajjar, D.P., Hazen, S.L., Hoff, H.F., Sharma, K., Silverstein, R.L. J. Clin. Invest. (2000) [Pubmed]
  7. Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain. Stuart, L.M., Deng, J., Silver, J.M., Takahashi, K., Tseng, A.A., Hennessy, E.J., Ezekowitz, R.A., Moore, K.J. J. Cell Biol. (2005) [Pubmed]
  8. Association between a novel 11-base pair deletion mutation in the promoter region of the scavenger receptor class B type I gene and plasma HDL cholesterol levels in Taiwanese Chinese. Hsu, L.A., Ko, Y.L., Wu, S., Teng, M.S., Peng, T.Y., Chen, C.F., Chen, C.F., Lee, Y.S. Arterioscler. Thromb. Vasc. Biol. (2003) [Pubmed]
  9. Charting the fate of the "good cholesterol": identification and characterization of the high-density lipoprotein receptor SR-BI. Krieger, M. Annu. Rev. Biochem. (1999) [Pubmed]
  10. The role of PPAR-gamma in macrophage differentiation and cholesterol uptake. Moore, K.J., Rosen, E.D., Fitzgerald, M.L., Randow, F., Andersson, L.P., Altshuler, D., Milstone, D.S., Mortensen, R.M., Spiegelman, B.M., Freeman, M.W. Nat. Med. (2001) [Pubmed]
  11. Overexpression of the HDL receptor SR-BI alters plasma HDL and bile cholesterol levels. Kozarsky, K.F., Donahee, M.H., Rigotti, A., Iqbal, S.N., Edelman, E.R., Krieger, M. Nature (1997) [Pubmed]
  12. Identification of CD36 as the first gene dependent on the B-cell differentiation factor Oct-2. König, H., Pfisterer, P., Corcoran, L.M., Wirth, T. Genes Dev. (1995) [Pubmed]
  13. Diet-induced occlusive coronary atherosclerosis, myocardial infarction, cardiac dysfunction, and premature death in scavenger receptor class B type I-deficient, hypomorphic apolipoprotein ER61 mice. Zhang, S., Picard, M.H., Vasile, E., Zhu, Y., Raffai, R.L., Weisgraber, K.H., Krieger, M. Circulation (2005) [Pubmed]
  14. Polysaccharides isolated from Phellinus gilvus inhibit melanoma growth in mice. Bae, J.S., Jang, K.H., Yim, H., Jin, H.K. Cancer Lett. (2005) [Pubmed]
  15. Scavenger receptor BI (SR-BI) is up-regulated in adrenal gland in apolipoprotein A-I and hepatic lipase knock-out mice as a response to depletion of cholesterol stores. In vivo evidence that SR-BI is a functional high density lipoprotein receptor under feedback control. Wang, N., Weng, W., Breslow, J.L., Tall, A.R. J. Biol. Chem. (1996) [Pubmed]
  16. Reconstituted discoidal ApoE-phospholipid particles are ligands for the scavenger receptor BI. The amino-terminal 1-165 domain of ApoE suffices for receptor binding. Li, X., Kan, H.Y., Lavrentiadou, S., Krieger, M., Zannis, V. J. Biol. Chem. (2002) [Pubmed]
  17. Accelerated lipid absorption in mice overexpressing intestinal SR-BI. Bietrix, F., Yan, D., Nauze, M., Rolland, C., Bertrand-Michel, J., Coméra, C., Schaak, S., Barbaras, R., Groen, A.K., Perret, B., Tercé, F., Collet, X. J. Biol. Chem. (2006) [Pubmed]
  18. Scavenger receptor BI (SR-BI) clustered on microvillar extensions suggests that this plasma membrane domain is a way station for cholesterol trafficking between cells and high-density lipoprotein. Peng, Y., Akmentin, W., Connelly, M.A., Lund-Katz, S., Phillips, M.C., Williams, D.L. Mol. Biol. Cell (2004) [Pubmed]
  19. Murine SR-BI, a high density lipoprotein receptor that mediates selective lipid uptake, is N-glycosylated and fatty acylated and colocalizes with plasma membrane caveolae. Babitt, J., Trigatti, B., Rigotti, A., Smart, E.J., Anderson, R.G., Xu, S., Krieger, M. J. Biol. Chem. (1997) [Pubmed]
  20. Up-regulation of peroxisome proliferator-activated receptors (PPAR-alpha) and PPAR-gamma messenger ribonucleic acid expression in the liver in murine obesity: troglitazone induces expression of PPAR-gamma-responsive adipose tissue-specific genes in the liver of obese diabetic mice. Memon, R.A., Tecott, L.H., Nonogaki, K., Beigneux, A., Moser, A.H., Grunfeld, C., Feingold, K.R. Endocrinology (2000) [Pubmed]
  21. TGF-beta reduced binding of high-density lipoproteins in murine macrophages and macrophage-derived foam cells. Zuckerman, S.H., Panousis, C., Evans, G. Atherosclerosis (2001) [Pubmed]
  22. Fenofibrate Reduces Atherogenesis in ApoE*3Leiden Mice: Evidence for Multiple Antiatherogenic Effects Besides Lowering Plasma Cholesterol. Kooistra, T., Verschuren, L., de Vries-van der Weij, J., Koenig, W., Toet, K., Princen, H.M., Kleemann, R. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  23. SR-BI protects against endotoxemia in mice through its roles in glucocorticoid production and hepatic clearance. Cai, L., Ji, A., de Beer, F.C., Tannock, L.R., van der Westhuyzen, D.R. J. Clin. Invest. (2008) [Pubmed]
  24. Regulation of SR-BI-mediated high-density lipoprotein metabolism by the tissue-specific adaptor protein PDZK1. Yesilaltay, A., Kocher, O., Rigotti, A., Krieger, M. Curr. Opin. Lipidol. (2005) [Pubmed]
  25. Cellular cholesterol regulates expression of the macrophage type B scavenger receptor, CD36. Han, J., Hajjar, D.P., Tauras, J.M., Nicholson, A.C. J. Lipid Res. (1999) [Pubmed]
  26. Acute P-407 administration to mice causes hypercholesterolemia by inducing cholesterolgenesis and down-regulating low-density lipoprotein receptor expression. Leon, C., Wasan, K.M., Sachs-Barrable, K., Johnston, T.P. Pharm. Res. (2006) [Pubmed]
  27. Scavenger receptor class B type I-mediated protection against atherosclerosis in LDL receptor-negative mice involves its expression in bone marrow-derived cells. Covey, S.D., Krieger, M., Wang, W., Penman, M., Trigatti, B.L. Arterioscler. Thromb. Vasc. Biol. (2003) [Pubmed]
  28. Low-density lipoprotein from apolipoprotein E-deficient mice induces macrophage lipid accumulation in a CD36 and scavenger receptor class A-dependent manner. Zhao, Z., de Beer, M.C., Cai, L., Asmis, R., de Beer, F.C., de Villiers, W.J., van der Westhuyzen, D.R. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  29. Induction of adrenal scavenger receptor BI and increased high density lipoprotein-cholesteryl ether uptake by in vivo inhibition of hepatic lipase. Vieira-van Bruggen, D., Kalkman, I., van Gent, T., van Tol, A., Jansen, H. J. Biol. Chem. (1998) [Pubmed]
  30. Leptin induces the hepatic high density lipoprotein receptor scavenger receptor B type I (SR-BI) but not cholesterol 7alpha-hydroxylase (Cyp7a1) in leptin-deficient (ob/ob) mice. Lundåsen, T., Liao, W., Angelin, B., Rudling, M. J. Biol. Chem. (2003) [Pubmed]
  31. Synthetic retinoid Am80 reduces scavenger receptor expression and atherosclerosis in mice by inhibiting IL-6. Takeda, N., Manabe, I., Shindo, T., Iwata, H., Iimuro, S., Kagechika, H., Shudo, K., Nagai, R. Arterioscler. Thromb. Vasc. Biol. (2006) [Pubmed]
  32. Loss of receptor-mediated lipid uptake via scavenger receptor A or CD36 pathways does not ameliorate atherosclerosis in hyperlipidemic mice. Moore, K.J., Kunjathoor, V.V., Koehn, S.L., Manning, J.J., Tseng, A.A., Silver, J.M., McKee, M., Freeman, M.W. J. Clin. Invest. (2005) [Pubmed]
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