Lipid peroxidation is increased in paraoxonase L55 homozygotes compared with M-allele carriers.
Human serum paraoxonase (PON) is an antioxidative enzyme, which circulates on high-density lipoproteins and appears to use oxidized phospholipids as physiological substrates. PON M/L55 substitution changes the ability of PON to prevent lipid oxidation. Urinary 8-iso-PGF(2alpha) (one of F2 -isoprostanes) may represent a non-invasive in vivo index of free radical generation and we propose that PON might influence the biosynthesis of 8-iso-PGF(2alpha) in the vasculature. We studied the urinary excretion of 8-iso-PGF(2alpha) and related it to PON M/L55 genotypes in patients with type 2 diabetes mellitus (n = 55) and non-diabetic control subjects (n = 55). Urinary 8-iso-PGF(2alpha) was determined by competitive ELISA and the PON genotype by a PCR based restriction enzyme digestion method. LL homozygotes were compared to M-allele carriers (ML heterozygotes and MM homozygotes). The urinary excretion of 8-iso-PGF(2alpha) among non-diabetic non-smoking LL homozygotes was 3995.5 +/- 3352.8 ng/24-hour and among M-allele carriers 1689.8 +/- 1051.3 ng/24-hour (p = 0.017, ANCOVA; gender, hypertension, total cholesterol, triglycerides and LDL cholesterol as covariates). The excretion of 8-iso-PGF(2alpha), was increased in type 2 diabetes mellitus compared to non-diabetic control subjects. PON may thus protect against oxidative stress by destroying some biologically active lipids. Excretion of 8-iso-PGF(2alpha) is increased in type 2 diabetes, which may reflect oxidant injury.
Malin
R
R
Tampere University Hospital, Centre for Laboratory Medicine, Department of Clinical Chemistry and University of Tampere, Medical School; P.O. Box 2000, 33521 Tampere, Finland.
Laine
S
S
Rantalaiho
V
V
Wirta
O
O
Pasternack
A
A
Jokela
H
H
Alho
H
H
Koivula
T
T
Lehtimäki
T
T
D043303:Aryldialkylphosphatase; D001205:Ascorbic Acid / Q000031:analogs & derivatives; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine*; D004950:Esterases / Q000097:blood / Q000235:genetics*; D028441:F2-Isoprostanes; D005260:Female; D005919:Glomerular Filtration Rate; D006720:Homozygote; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D011897:Random Allocation; D012016:Reference Values; D012907:Smoking
D028441:F2-Isoprostanes; C075750:8-epi-prostaglandin F2alpha; C087337:6-S-hexadecyl-2-methoxythioascorbic acid; D015237:Dinoprost; D004950:Esterases; D043303:Aryldialkylphosphatase; D001205:Ascorbic Acid