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Immunoassay, inhibition and mechanis...
~
Balamraju, Yuvaraju.
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Immunoassay, inhibition and mechanistic studies of low density lipoprotein oxidation.
Record Type:
Electronic resources : Monograph/item
Title/Author:
Immunoassay, inhibition and mechanistic studies of low density lipoprotein oxidation./
Author:
Balamraju, Yuvaraju.
Description:
178 p.
Notes:
Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 6055.
Contained By:
Dissertation Abstracts International64-12B.
Subject:
Chemistry, General. -
Online resource:
http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3118122
ISBN:
0496655460
Immunoassay, inhibition and mechanistic studies of low density lipoprotein oxidation.
Balamraju, Yuvaraju.
Immunoassay, inhibition and mechanistic studies of low density lipoprotein oxidation.
- 178 p.
Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 6055.
Thesis (Ph.D.)--Case Western Reserve University, 2004.
Oxidation of human low density lipoprotein (LDL) produces a large variety of aldehydic products, such as 2-hydroxyaldehydes, 4-hydroxy-2-nonenal, and phospholipid esters of 9-hydroxy-12-oxododec-10-enoic acid (HODA) or isolevuglandins, that are capable of modifying the LDL protein apolipoprotein (apoB) by covalent adduction. Such modifications are believed to play key roles in aging and pathophysiologic processes, such as atherogenesis.
ISBN: 0496655460Subjects--Topical Terms:
1021807
Chemistry, General.
Immunoassay, inhibition and mechanistic studies of low density lipoprotein oxidation.
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Immunoassay, inhibition and mechanistic studies of low density lipoprotein oxidation.
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178 p.
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Source: Dissertation Abstracts International, Volume: 64-12, Section: B, page: 6055.
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Adviser: Robert G. Salomon.
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Thesis (Ph.D.)--Case Western Reserve University, 2004.
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Oxidation of human low density lipoprotein (LDL) produces a large variety of aldehydic products, such as 2-hydroxyaldehydes, 4-hydroxy-2-nonenal, and phospholipid esters of 9-hydroxy-12-oxododec-10-enoic acid (HODA) or isolevuglandins, that are capable of modifying the LDL protein apolipoprotein (apoB) by covalent adduction. Such modifications are believed to play key roles in aging and pathophysiologic processes, such as atherogenesis.
520
$a
With enzyme-linked immunosorbent assays, we show that 4-butyl-3-hydroxy-5-pentylpyridinium (Py) derivatives are formed in 2-hydroxyheptanal-treated LDL, in bovine serum albumin treated with oxidation products from linoleic acid, and in Cu 2+ or lipoxygenase-mediated oxidation of LDL. We also detected Py adducts in human plasma.
520
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Antioxidants prevent protein damage by curtailing the free radical-induced generation of electrophilic lipid oxidation products. In contrast, taurine, creatine and carnosine act as traps, " antielectrophiles", that competitively inhibit the reactions of these toxic electrophiles with protein-based nucleophiles. None of the antielectrophiles effectively trap isolevuglandins because these extremely reactive membrane-bound compounds react rapidly with membrane-bound protein. Furthermore, the finding that isolevuglandins are generated in the presence of taurine, creatine and camosine establishes the fact that these compounds are not antioxidants. To enhance the proclivity of antielectrophiles to associate with membranes, we synthesized a series of acyl histidines with lipophilic tails of various lengths. We found that any slight impurity of histidine in the acyl histidine derivatives could cause lowering of the HODA-derived epitopes when the oxidation of LDL was carried out with Cu2+. This is because histidine inhibits the oxidation of LDL by Cu2+, presumably because it can form a complex with Cu2+ ions. Support for this view was provided by the fact that LDL oxidation promoted by myeloperoxidase is not inhibited by histidine or the putative acylhistidine antielectrophiles.
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We employed a model system, consisting of a (E)-4-hydroxy-4-methyl-1-phenyl-2-penten-1-one (HMPP) and anisaldehyde to test a mechanistic hypothesis for the formation of 9-oxononanoic acid esters of 2-lysophosphatidylcholine (PC) by oxidative fragmentation of HODA-PC. As hypothesized, fragmentation of HMPP with formation of acetone occurred only upon incubation in the presence of oxygen and anisaldehyde. HMPP apparently undergoes Michael addition of an aldehyde-derived acylperoxy radical leading to generation of acetone by fragmentation of a beta-hydroxyperester.
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School code: 0042.
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Chemistry, General.
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Chemistry, Organic.
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http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3118122
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