title: Identification and quantification of regioisomeric cholesteryl linoleate hydroperoxides in oxidized human low density lipoprotein and high density lipoprotein.
abstract: Oxidation of human LDL is implicated as an initiator of atherosclerosis. Isolated low density lipoprotein (LDL) and high density lipoprotein (HDL2) were exposed to aqueous radicals generated from the thermolabile azo compound 2,2'-azobis(2-amidinopropane) dihydrochloride. The primary nonpolar lipid products formed from the autoxidation of LDL and HDL were the regioisomeric cholesteryl linoleate hydroperoxides. In LDL oxidations, 9- and 13-hydroperoxides with trans,cis conjugated diene were formed as the major oxidation products if endogenous alpha-tocopheral was present in the LDL. After extended oxidation of LDL, at the time when endogenous alpha-tocopherol was consumed, the two trans,cis conjugated diene hydroperoxides began to disappear and the 9- and 13-hydroperoxides with trans,trans conjugated diene appeared. At very long oxidation times, none of the primary products, the conjugated diene hydroperoxides, were present. In HDL2, which has only very low levels of antioxidants, both the 9- and 13-hydroperoxides with trans,cis conjugated diene and the 9- and 13-hydroperoxides with trans,trans conjugated diene were formed at early stages of oxidation. The corresponding alcohols were also formed in the HDL2 oxidations. A mechanistic hypothesis consistent with these observations is presented.
authors.affiliation: Department of Chemistry, Paul M. Gross Laboratories, Duke University, Durham, North Carolina, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Kenar
authors.forename: C M
authors.initials: CM
authors.lastname: Havrilla
authors.forename: N A
authors.initials: NA
authors.lastname: Porter
authors.forename: J R
authors.initials: JR
authors.lastname: Guyton
authors.forename: S A
authors.initials: SA
authors.lastname: Brown
authors.forename: K F
authors.initials: KF
authors.lastname: Klemp
authors.forename: E
authors.initials: E
authors.lastname: Selinger
mesh_terms: D000438:Alcohols / Q000737:chemistry; D000578:Amidines / Q000737:chemistry; D002073:Butanes; D002788:Cholesterol Esters / Q000032:analysis* / Q000737:chemistry*; D008076:Cholesterol, HDL / Q000737:chemistry*; D008078:Cholesterol, LDL / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005609:Free Radicals / Q000737:chemistry; D006801:Humans; D007536:Isomerism; D008054:Lipid Peroxides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009589:Nitrogen Oxides / Q000737:chemistry; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors; D014316:Tritium
chemical_list: D000438:Alcohols; D000578:Amidines; D002073:Butanes; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005609:Free Radicals; D008054:Lipid Peroxides; D009589:Nitrogen Oxides; D010545:Peroxides; D017382:Reactive Oxygen Species; D014316:Tritium; C007539:di-t-butyl nitroxide; C021976:cholesteryl linoleate; C046728:2,2'-azobis(2-amidinopropane)