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词条 OLR1
释义

  1. Function

  2. Clinical significance

  3. References

  4. Further reading

{{Infobox_gene}}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.[1][2]

LOX-1 is the main receptor for oxidized LDL on endothelial cells, macrophages, smooth muscle cells,[2] and other cell types.[3] But minimally oxidized LDL is more readily recognized by the TLR4 receptor, and highly oxidized LDL is more readily recognized by the CD36 receptor.[4]

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.

Normally, LOX-1 expression on endothelial cells is low, but tumor necrosis factor alpha, oxidized LDL, blood vessel sheer stress, and other atherosclerotic stimuli substantially increase LOX-1 expression.[3][5]

LOX-1 may be involved in the regulation of Fas-induced apoptosis. Oxidized LDL induces endothelial cell apoptosis through LOX-1 binding.[2] Other ligands for LOX-1 include oxidized high-density lipoprotein, advanced glycation end-products, platelets, and apoptotic cells.[2]

The binding of platelets to LOX-1 causes a release of vasoconstrictive endothelin, which induces endothelial dysfunction.

This protein may play a role as a scavenger receptor.[2]

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).[3] Macrophage affinity for unmodified LDL particles is low, but is greatly increased when the LDL particles are oxidized.[6] LDL oxidation occurs in the sub-endothelial space, rather than in the circulation. But oxidized cholesterol from foods cooked at high temperature can also be a source of oxysterols.[4]

Mutations of the OLR1 gene have been associated with atherosclerosis, risk of myocardial infarction, and may modify the risk of Alzheimer's disease.[7] 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,[8] but this has not yet been demonstrated in a living animal or human.

References

1. ^{{cite journal | vauthors = Li X, Bouzyk MM, Wang X | title = 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 | journal = Cytogenet Cell Genet | volume = 82 | issue = 1–2 | pages = 34–6 |date=Nov 1998 | pmid = 9763655 | pmc = | doi =10.1159/000015059 }}
2. ^1 2 {{cite journal | vauthors=Pirillo A, Norata GD, Catapano AL | title=LOX-1, OxLDL, and atherosclerosis | journal= Mediators of Inflammation | volume=2013 | pages=1–12 | year=2013 | url = https://www.hindawi.com/journals/mi/2013/152786/ | doi=10.1155/2013/152786 | pmc= 3723318 | pmid = 23935243 }}
3. ^1 2 {{cite journal | vauthors=Xu S, Ogura S, Chen J, Little PJ, Moss J, Liu P | title=LOX-1 in atherosclerosis: biological functions and pharmacological modifiers | journal= Cellular and Molecular Life Sciences | volume=70 | issue=16 | pages=2859–2872 | year=2013 | url = https://www.hindawi.com/journals/mi/2013/152786/ | doi=10.1007/s00018-012-1194-z | pmid = 23124189 | pmc=4142049 }}
4. ^1 {{cite journal | vauthors=Zmysłowski A, Szterk A | title=Current knowledge on the mechanism of atherosclerosis and pro-atherosclerotic properties of oxysterols | journal= Lipids in Health and Disease | volume=16 | issue=1 | pages=188 | year=2017 | doi=10.1186/s12944-017-0579-2 | pmc = 5625595 | pmid = 28969682 }}
5. ^{{cite journal | vauthors=Kakutani M, Masaki T, Sawamura T | title=A platelet-endothelium interaction mediated by lectin-like oxidized low-density lipoprotein receptor-1 | journal= Proceedings of the National Academy of Sciences of the United States of America | volume=97 | issue=1 | pages=360–364 | year=2000 |url=http://www.pnas.org/content/97/1/360.long | doi=10.1016/j.biochi.2016.10.010 | pmc=26668 | pmid = 10618423}}
6. ^{{cite journal | vauthors=Brites F, Martin M, Guillas I, Kontush A | title=Antioxidative activity of high-density lipoprotein (HDL): Mechanistic insights into potential clinical benefit | journal= BBA Clinical | volume=8 | pages=66–77 | year=2017 | url = https://www.sciencedirect.com/science/article/pii/S2214647417300326 | doi=10.1016/j.bbacli.2017.07.002 | pmc= 5597817 | pmid = 28936395 }}
7. ^1 2 {{cite web | title = Entrez Gene: OLR1 oxidized low density lipoprotein (lectin-like) receptor 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4973| accessdate = }}
8. ^{{cite journal|vauthors=Guan S, Wang B, Li W, Guan J, Fang X|title=Effects of berberine on expression of LOX-1 and SR-BI in human macrophage-derived foam cells induced by ox-LDL|journal=Am J Chin Med|date=2010|volume=38|issue=6|pages=1161–9|pmid=21061468|doi=10.1142/s0192415x10008548}}

Further reading

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