Lipid hydroperoxy and hydroxy derivatives in copper-catalyzed oxidation of low density lipoprotein.
Oxidation of low density lipoprotein (LDL) causes changes in the biological properties of LDL that may be important in atherogenesis. That LDL oxidation is accompanied by lipid peroxidation has been demonstrated, but previous analyses of the products of LDL oxidation have not included measurement of specific lipid hydroperoxy and hydroxy derivatives. In this study, LDL was isolated from plasma of normal volunteers and exposed to oxygenated buffer and 5 microM CuSO4 for 24 h. Oxidized LDL showed decreased linoleate (18:2) and arachidonate (20:4) content with increased concentrations of thiobarbituric acid reactive substances (TBARS) and hydroxy and hydroperoxy 18:2 and 20:4. The electrophoretic mobility of the LDL protein also was increased by oxidation. After reduction, the hydroxy fatty acids were characterized by gas chromatography-mass spectrometric analysis of the trimethylsilyl ether methyl ester derivatives. The hydroperoxy and hydroxy derivatives accounted for approximately 70% of the linoleate consumed during LDL oxidation and represented 45-fold more product than was measured by TBARS analysis. Numerous biological properties, including cytotoxic and chemoattractant activities of hydroperoxy and hydroxy fatty acids, have been reported, but the manner in which they may contribute to atherogenesis requires further study.
Lenz
M L
ML
Department of Medicine, Baylor College of Medicine, Houston, TX 77030.
Hughes
H
H
Mitchell
J R
JR
Via
D P
DP
Guyton
J R
JR
Taylor
A A
AA
Gotto
A M
AM
Smith
C V
CV
D001095:Arachidonic Acids / Q000378:metabolism*; D002384:Catalysis; D003300:Copper; D006801:Humans; D008041:Linoleic Acids / Q000378:metabolism*; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*
D001095:Arachidonic Acids; D008041:Linoleic Acids; D008077:Lipoproteins, LDL; D003300:Copper