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'''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]].<ref name="pmid9763655">{{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 }}</ref><ref name="entrez" /> | '''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]].<ref name="pmid9763655">{{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 }}</ref><ref name="entrez" /> | ||
LOX-1 is the main receptor for oxidized LDL on [[endothelium|endothelial cells]], [[macrophage]]s, [[smooth muscle tissue|smooth muscle cells]],<ref name="pmid23935243">{{cite journal | vauthors=Pirillo A, Norata GD, Catapano AL | title=LOX-1, OxLDL, and atherosclerosis | journal= Mediators of Inflammation | volume=2013 | pages=152786 | year=2013 | url = https://www.hindawi.com/journals/mi/2013/152786/ | doi=10.1155/2013/152786 | PMC= 3723318 | PMID = 23935243 }}</ref> and other cell types.<ref name="pmid23124189">{{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 }}</ref> But minimally oxidized LDL is more readily recognized by the [[TLR4]] receptor, and highly oxidized LDL is more readily recognized by the [[CD36]] receptor.<ref name="pmid28969682">{{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 }}</ref> | |||
== Function == | == Function == | ||
LOX-1 is a receptor protein which belongs to the [[C-type lectin|C-type lectin superfamily]]. Its gene is regulated through the cyclic AMP signaling pathway. The protein binds, internalizes and degrades [[Redox|oxidized]] [[low-density lipoprotein]]. | |||
LOX-1 is | 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.<ref name="pmid23124189" /><ref name="pmid10618423 ">{{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}}</ref> | ||
LOX-1 may be involved in the regulation of [[Fas ligand|Fas]]-induced [[apoptosis]]. Oxidized LDL induces endothelial cell apoptosis through LOX-1 binding.<ref name="pmid23935243" /> Other [[ligand]]s for LOX-1 include oxidized [[high-density lipoprotein]], [[advanced glycation end-product]]s, [[platelet]]s, and apoptotic cells.<ref name="pmid23935243" /><ref name="pmid10618423" /> | |||
The binding of platelets to LOX-1 causes a release of vasoconstrictive [[endothelin]], which induces [[endothelial dysfunction]].<ref name="pmid10618423" /> | |||
This protein may play a role as a scavenger receptor.<ref name="entrez"/> | |||
== Clinical significance == | == 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).<ref name="pmid23124189" /> Macrophage affinity for unmodified LDL particles is low, but is greatly increased when the LDL particles are oxidized.<ref name="pmid28936395">{{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?via%3Dihub | doi=10.1016/j.bbacli.2017.07.002 | PMC= 5597817 | PMID = 28936395 }}</ref> LDL oxidation occurs in the sub-endothelial space, rather than in the circulation.<ref name="pmid28936395 " /> But oxidized cholesterol from foods cooked at high temperature can also be a source of [[oxysterol]]s.<ref name="pmid28969682" /> | |||
Mutations of the OLR1 gene have been associated with [[atherosclerosis]], risk of [[myocardial infarction]], and may modify the risk of [[Alzheimer's disease]].<ref name="entrez">{{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 = }}</ref> When applied to human macrophage-derived foam cells ''in vitro'', the [[dietary supplement]] [[berberine]] inhibits the [[Gene expression|expression]] of the ORL1 gene in response to oxidized [[low-density lipoprotein cholesterol]],<ref name=Guan2010>{{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}}<!--|accessdate=11 October 2015--></ref> but this has not yet been demonstrated in a living animal or human. | Mutations of the OLR1 gene have been associated with [[atherosclerosis]], risk of [[myocardial infarction]], and may modify the risk of [[Alzheimer's disease]].<ref name="entrez">{{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 = }}</ref> When applied to human macrophage-derived foam cells ''in vitro'', the [[dietary supplement]] [[berberine]] inhibits the [[Gene expression|expression]] of the ORL1 gene in response to oxidized [[low-density lipoprotein cholesterol]],<ref name=Guan2010>{{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}}<!--|accessdate=11 October 2015--></ref> but this has not yet been demonstrated in a living animal or human. | ||
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[[Category:C-type lectins]] | [[Category:C-type lectins]] | ||
[[Category:Heart diseases]] | |||
Latest revision as of 07:41, 6 September 2018
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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,[3] and other cell types.[4] But minimally oxidized LDL is more readily recognized by the TLR4 receptor, and highly oxidized LDL is more readily recognized by the CD36 receptor.[5]
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.[4][6]
LOX-1 may be involved in the regulation of Fas-induced apoptosis. Oxidized LDL induces endothelial cell apoptosis through LOX-1 binding.[3] Other ligands for LOX-1 include oxidized high-density lipoprotein, advanced glycation end-products, platelets, and apoptotic cells.[3][6] The binding of platelets to LOX-1 causes a release of vasoconstrictive endothelin, which induces endothelial dysfunction.[6]
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).[4] Macrophage affinity for unmodified LDL particles is low, but is greatly increased when the LDL particles are oxidized.[7] LDL oxidation occurs in the sub-endothelial space, rather than in the circulation.[7] But oxidized cholesterol from foods cooked at high temperature can also be a source of oxysterols.[5]
Mutations of the OLR1 gene have been associated with atherosclerosis, risk of myocardial infarction, and may modify the risk of Alzheimer's disease.[2] 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
- ↑ 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.
- ↑ 2.0 2.1 2.2 "Entrez Gene: OLR1 oxidized low density lipoprotein (lectin-like) receptor 1".
- ↑ 3.0 3.1 3.2 Pirillo A, Norata GD, Catapano AL (2013). "LOX-1, OxLDL, and atherosclerosis". Mediators of Inflammation. 2013: 152786. doi:10.1155/2013/152786. PMC 3723318. PMID 23935243.
- ↑ 4.0 4.1 4.2 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.
- ↑ 5.0 5.1 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.
- ↑ 6.0 6.1 6.2 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. doi:10.1016/j.biochi.2016.10.010. PMC 26668. PMID 10618423.
- ↑ 7.0 7.1 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.
- ↑ 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.
- Sawamura T, Kume N, Aoyama T, et al. (1997). "An endothelial receptor for oxidized low-density lipoprotein". Nature. 386 (6620): 73–7. doi:10.1038/386073a0. PMID 9052782.
- 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. 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.
- 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. 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.
- 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.
