OLR1

OLR1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesOLR1, CLEC8A, LOX1, LOXIN, SCARE1, SLOX1, oxidized low density lipoprotein receptor 1
External IDsOMIM: 602601; MGI: 1261434; HomoloGene: 1910; GeneCards: OLR1; OMA:OLR1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

4973

108078

Ensembl

ENSG00000173391

ENSMUSG00000030162

UniProt

P78380

Q9EQ09

RefSeq (mRNA)

NM_001172632
NM_001172633
NM_002543

NM_001301094
NM_001301096
NM_138648

RefSeq (protein)

NP_001166103
NP_001166104
NP_002534

NP_001288023
NP_001288025
NP_619589

Location (UCSC)Chr 12: 10.16 – 10.17 MbChr 6: 129.46 – 129.48 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Oxidized low-density lipoprotein receptor 1 (Ox-LDL receptor 1) also known as lectin-type oxidized LDL receptor 1 (LOX-1) is a protein that in humans is encoded by the OLR1 gene.[5][6]

LOX-1 is the main receptor for oxidized LDL on endothelial cells, macrophages, smooth muscle cells,[7] and other cell types.[8] But minimally oxidized LDL is more readily recognized by the TLR4 receptor, and highly oxidized LDL is more readily recognized by the CD36 receptor.[9]

Function

LOX-1 is a receptor protein which belongs to the C-type lectin superfamily. Its gene is regulated through the cyclic AMP signaling pathway. The protein binds, internalizes and degrades oxidized low-density lipoprotein.[citation needed]

Normally, LOX-1 expression on endothelial cells is low, but tumor necrosis factor alpha, oxidized LDL, blood vessel shear stress, and other atherosclerotic stimuli substantially increase LOX-1 expression.[8][10]

LOX-1 may be involved in the regulation of Fas-induced apoptosis. Oxidized LDL induces endothelial cell apoptosis through LOX-1 binding.[7] Other ligands for LOX-1 include oxidized high-density lipoprotein, advanced glycation end-products, platelets, and apoptotic cells.[7][10] The binding of platelets to LOX-1 causes a release of vasoconstrictive endothelin, which induces endothelial dysfunction.[10]

This protein may play a role as a scavenger receptor.[6]

Clinical significance

Binding of oxidized LDL to LOX-1 activates NF-κB, leading to monocyte adhesion to enthothelial cells (a pre-requisite for the macrophage foam cell formation of atherosclerosis).[8] Macrophage affinity for unmodified LDL particles is low, but is greatly increased when the LDL particles are oxidized.[11] LDL oxidation occurs in the sub-endothelial space, rather than in the circulation.[11] But oxidized cholesterol from foods cooked at high temperature can also be a source of oxysterols.[9]

Mutations of the OLR1 gene have been associated with atherosclerosis, risk of myocardial infarction, and may modify the risk of Alzheimer's disease.[6] When applied to human macrophage-derived foam cells in vitro, the dietary supplement berberine inhibits the expression of the ORL1 gene in response to oxidized low-density lipoprotein cholesterol,[12] but this has not yet been demonstrated in a living animal or human.[citation needed]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000173391 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030162 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Li X, Bouzyk MM, Wang X (Nov 1998). "Assignment of the human oxidized low-density lipoprotein receptor gene (OLR1) to chromosome 12p13.1→p12.3, and identification of a polymorphic CA-repeat marker in the OLR1 gene". Cytogenet Cell Genet. 82 (1–2): 34–6. doi:10.1159/000015059. PMID 9763655. S2CID 46772688.
  6. ^ a b c "Entrez Gene: OLR1 oxidized low density lipoprotein (lectin-like) receptor 1".
  7. ^ a b c Pirillo A, Norata GD, Catapano AL (2013). "LOX-1, OxLDL, and atherosclerosis". Mediators of Inflammation. 2013: 1–12. doi:10.1155/2013/152786. PMC 3723318. PMID 23935243.
  8. ^ a b c Xu S, Ogura S, Chen J, Little PJ, Moss J, Liu P (2013). "LOX-1 in atherosclerosis: biological functions and pharmacological modifiers". Cellular and Molecular Life Sciences. 70 (16): 2859–2872. doi:10.1007/s00018-012-1194-z. PMC 4142049. PMID 23124189.
  9. ^ a b Zmysłowski A, Szterk A (2017). "Current knowledge on the mechanism of atherosclerosis and pro-atherosclerotic properties of oxysterols". Lipids in Health and Disease. 16 (1): 188. doi:10.1186/s12944-017-0579-2. PMC 5625595. PMID 28969682.
  10. ^ a b c Kakutani M, Masaki T, Sawamura T (2000). "A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1". Proceedings of the National Academy of Sciences of the United States of America. 97 (1): 360–364. Bibcode:2000PNAS...97..360K. doi:10.1016/j.biochi.2016.10.010. PMC 26668. PMID 10618423.
  11. ^ a b Brites F, Martin M, Guillas I, Kontush A (2017). "Antioxidative activity of high-density lipoprotein (HDL): Mechanistic insights into potential clinical benefit". BBA Clinical. 8: 66–77. doi:10.1016/j.bbacli.2017.07.002. PMC 5597817. PMID 28936395.
  12. ^ Guan S, Wang B, Li W, Guan J, Fang X (2010). "Effects of berberine on expression of LOX-1 and SR-BI in human macrophage-derived foam cells induced by ox-LDL". Am J Chin Med. 38 (6): 1161–9. doi:10.1142/s0192415x10008548. PMID 21061468.

Further reading

  • Sawamura T (2002). "[Molecular identification of LOX-1 and analysis of its pathophysiological role]". Nippon Yakurigaku Zasshi. 119 (3): 145–54. doi:10.1254/fpj.119.145. PMID 11915516.
  • Mehta JL, Li D (2002). "Identification, regulation and function of a novel lectin-like oxidized low-density lipoprotein receptor". J. Am. Coll. Cardiol. 39 (9): 1429–35. doi:10.1016/S0735-1097(02)01803-X. PMID 11985903.
  • Sawamura T (2002). "[LOX-1: the oxidized LDL receptor expressed in vascular endothelial cells]". Seikagaku. 74 (5): 365–76. PMID 12073608.
  • Ando K, Fujita T (2005). "Role of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in the development of hypertensive organ damage". Clin. Exp. Nephrol. 8 (3): 178–82. doi:10.1007/s10157-004-0288-9. PMID 15480893. S2CID 24851728.
  • Sawamura T, Kume N, Aoyama T, et al. (1997). "An endothelial receptor for oxidized low-density lipoprotein". Nature. 386 (6620): 73–7. Bibcode:1997Natur.386...73S. doi:10.1038/386073a0. PMID 9052782. S2CID 4321933.
  • Yoshida H, Kondratenko N, Green S, et al. (1998). "Identification of the lectin-like receptor for oxidized low-density lipoprotein in human macrophages and its potential role as a scavenger receptor". Biochem. J. 334 (Pt 1) (Pt 1): 9–13. doi:10.1042/bj3340009. PMC 1219654. PMID 9693095.
  • Mehta JL, Li DY (1998). "Identification and autoregulation of receptor for OX-LDL in cultured human coronary artery endothelial cells". Biochem. Biophys. Res. Commun. 248 (3): 511–4. doi:10.1006/bbrc.1998.9004. PMID 9703956.
  • Yamanaka S, Zhang XY, Miura K, et al. (1999). "The human gene encoding the lectin-type oxidized LDL receptor (OLR1) is a novel member of the natural killer gene complex with a unique expression profile". Genomics. 54 (2): 191–9. doi:10.1006/geno.1998.5561. PMID 9828121.
  • Nagase M, Abe J, Takahashi K, et al. (1999). "Genomic organization and regulation of expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) gene". J. Biol. Chem. 273 (50): 33702–7. doi:10.1074/jbc.273.50.33702. PMID 9837956.
  • Draude G, Hrboticky N, Lorenz RL (1999). "The expression of the lectin-like oxidized low-density lipoprotein receptor (LOX-1) on human vascular smooth muscle cells and monocytes and its down-regulation by lovastatin". Biochem. Pharmacol. 57 (4): 383–6. doi:10.1016/S0006-2952(98)00313-X. PMID 9933026.
  • Aoyama T, Sawamura T, Furutani Y, et al. (1999). "Structure and chromosomal assignment of the human lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) gene". Biochem. J. 339 (Pt 1) (Pt 1): 177–84. doi:10.1042/0264-6021:3390177. PMC 1220142. PMID 10085242.
  • Li DY, Zhang YC, Philips MI, et al. (1999). "Upregulation of endothelial receptor for oxidized low-density lipoprotein (LOX-1) in cultured human coronary artery endothelial cells by angiotensin II type 1 receptor activation". Circ. Res. 84 (9): 1043–9. doi:10.1161/01.res.84.9.1043. PMID 10325241.
  • Kataoka H, Kume N, Miyamoto S, et al. (1999). "Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions". Circulation. 99 (24): 3110–7. doi:10.1161/01.cir.99.24.3110. PMID 10377073.
  • Li D, Saldeen T, Romeo F, Mehta JL (2000). "Oxidized LDL upregulates angiotensin II type 1 receptor expression in cultured human coronary artery endothelial cells: the potential role of transcription factor NF-kappaB". Circulation. 102 (16): 1970–6. doi:10.1161/01.cir.102.16.1970. PMID 11034947.
  • Bull C, Sobanov Y, Röhrdanz B, et al. (2001). "The centromeric part of the human NK gene complex: linkage of LOX-1 and LY49L with the CD94/NKG2 region". Genes Immun. 1 (4): 280–7. doi:10.1038/sj.gene.6363678. PMID 11196705. S2CID 21961232.
  • Shi X, Niimi S, Ohtani T, Machida S (2001). "Characterization of residues and sequences of the carbohydrate recognition domain required for cell surface localization and ligand binding of human lectin-like oxidized LDL receptor". J. Cell Sci. 114 (Pt 7): 1273–82. doi:10.1242/jcs.114.7.1273. PMID 11256994.
  • Chen M, Narumiya S, Masaki T, Sawamura T (2001). "Conserved C-terminal residues within the lectin-like domain of LOX-1 are essential for oxidized low-density-lipoprotein binding". Biochem. J. 355 (Pt 2): 289–96. doi:10.1042/0264-6021:3550289. PMC 1221738. PMID 11284714.
  • Tanimoto A, Murata Y, Nomaguchi M, et al. (2001). "Histamine increases the expression of LOX-1 via H2 receptor in human monocytic THP-1 cells". FEBS Lett. 508 (3): 345–9. doi:10.1016/S0014-5793(01)03073-3. PMID 11728449. S2CID 7257298.
  • Sobanov Y, Bernreiter A, Derdak S, et al. (2002). "A novel cluster of lectin-like receptor genes expressed in monocytic, dendritic and endothelial cells maps close to the NK receptor genes in the human NK gene complex". Eur. J. Immunol. 31 (12): 3493–503. doi:10.1002/1521-4141(200112)31:12<3493::AID-IMMU3493>3.0.CO;2-9. PMID 11745369. S2CID 42415487.
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