JPVYNHNXODAKFH-UHFFFAOYSA-N |
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cofactor
An organic molecule or ion (usually a metal ion) that is required by an enzyme for its activity. It may be attached either loosely (coenzyme) or tightly (prosthetic group).
(via copper cation )
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View more via ChEBI Ontology
copper(II) cation
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copper(2+)
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copper(2+) ion
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COPPER (II) ION
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PDBeChem
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copper(II) cation
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ChEBI
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copper, ion (Cu2+)
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ChemIDplus
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Cu(II)
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ChEBI
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Cu2+
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ChEBI
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Cu2+
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UniProt
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cupric ion
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ChEBI
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15158-11-9
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CAS Registry Number
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ChemIDplus
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3587177
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Reaxys Registry Number
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Reaxys
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6855
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Gmelin Registry Number
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Gmelin
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Kummu O, Turunen SP, Prus P, Lehtimäki J, Veneskoski M, Wang C, Hörkkö S (2014) Human monoclonal Fab and human plasma antibodies to carbamyl-epitopes cross-react with malondialdehyde-adducts. Immunology 141, 416-430 [PubMed:24168430] [show Abstract] Oxidized low-density lipoprotein (OxLDL) plays a crucial role in the development of atherosclerosis. Carbamylated LDL has been suggested to promote atherogenesis in patients with chronic kidney disease. Here we observed that plasma IgG and IgM antibodies to carbamylated epitopes were associated with IgG and IgM antibodies to oxidation-specific epitopes (ρ = 0·65-0·86, P < 0·001) in healthy adults, suggesting a cross-reaction between antibodies recognizing carbamyl-epitopes and malondialdehyde (MDA)/malondialdehyde acetaldehyde (MAA) -adducts. We used a phage display technique to clone a human Fab antibody that bound to carbamylated LDL and other carbamylated proteins. Anti-carbamyl-Fab (Fab106) cross-reacted with oxidation-specific epitopes, especially with MDA-LDL and MAA-LDL. We showed that Fab106 bound to apoptotic Jurkat cells known to contain these oxidation-specific epitopes, and the binding was competed with soluble carbamylated and MDA-/MAA-modified LDL and BSA. In addition, Fab106 was able to block the uptake of carbamyl-LDL and MDA-LDL by macrophages and stained mouse atherosclerotic lesions. The observed cross-reaction between carbamylated and MDA-/MAA-modified LDL and its contribution to enhanced atherogenesis in uraemic patients require further investigation. | Wang C, Turunen SP, Kummu O, Veneskoski M, Lehtimäki J, Nissinen AE, Hörkkö S (2013) Natural antibodies of newborns recognize oxidative stress-related malondialdehyde acetaldehyde adducts on apoptotic cells and atherosclerotic plaques. International immunology 25, 575-587 [PubMed:23900424] [show Abstract] Malondialdehyde acetaldehyde (MAA) adducts are generated under oxidative stress and shown to be highly immunogenic. Our aim was to investigate the recognition of MAA adducts by human natural antibodies in newborns before or at the time of full-term pregnancy. Plasma samples of pre-term (n = 11) and full-term (n = 36) newborns were enriched in specific IgM binding to MAA adducts compared with the maternal plasma IgM levels. Umbilical cord blood lymphocyte phage display library was generated to clone Fabs that specifically recognized MAA adducts without cross-reactivity to malondialdehyde. Fab clones from the antibody libraries of the pre-term and full-term newborns showed high sequence homology to the germline genes encoding the variable regions of antibodies, confirming that these Fabs represented the natural antibody repertoire of human fetuses. The MAA-specific umbilical cord blood Fabs bound to apoptotic human endothelial cells and the binding was efficiently competed with MAA adducts. The MAA-specific Fabs also recognized epitopes on advanced atherosclerotic lesions, and the uptake of infrared (IR)-labeled MAA-low-density lipoprotein by mouse J774A.1 macrophages was significantly reduced in the presence of these Fabs. In conclusion, MAA adducts were identified as one of the major antigenic targets for human natural antibodies already before the time of birth. MAA-specific natural antibodies are suggested to regulate apoptotic cell clearance starting from fetal development and to participate in the immunomodulation of atherosclerosis development during adulthood. |
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