Do E-series prostaglandins and their metabolites influence oxidation of native and glycated low-density lipoproteins?
Oxidation of lipoproteins, and, in particular, low-density lipoproteins (LDL), has been shown to play a significant role in the pathogenesis of atherosclerosis. Oxidized LDL are endocytosed via scavenger receptors to form lipid-laden foam cells. The non-enzymatic reaction of glucose with proteins and lipoproteins results in a modified LDL involved in the pathogenesis of late complications in diabetes mellitus. In the present paper, the influence of various E-series prostaglandins (PGE1; 13,14-dihydro PGE1; 13,14-dihydro 15-keto PGE1; and PGE2) on oxidation of native and glycated LDL was investigated. The effect of these agents in the concentration range from 1 pg/mL to 1.6 micrograms/mL on copper-induced oxidation of native and glycated LDL was tested. The concentration of each agent causing the maximal effect on oxidation of native LDL, as measured by the formation of thiobarbituric acid-reacting substances, was chosen to estimate the effect on 2, 4, 8, and 24 h oxidation of glycated LDL. The study was performed with LDL isolated by sequential ultracentrifugation from normolipidemic individuals. LDL (0.25 mg protein/mL) was oxidatively modified with 5 microM CuSO4. The glycosylation of LDL was performed by incubation of LDL with 500 mM glucose for varying periods of time ranging from 10 to 31 days. Our results show that only 13,14-dihydro PGE1 significantly inhibits copper-induced oxidation of native LDL, while the other examined E-series prostaglandins in vitro are ineffective as reducing agents in LDL-oxidation.
Sobal
G
G
Department of Nuclear Medicine, University of Vienna, Austria.
Menzel
J E
JE
Sinzinger
H
H
D000328:Adult; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D011458:Prostaglandins E / Q000378:metabolism / Q000494:pharmacology*
D008077:Lipoproteins, LDL; D011458:Prostaglandins E; D005947:Glucose