Article

Mechanisms of oxidative modification of low density lipoproteins under conditions of oxidative and carbonyl stress

Biochemistry (Moscow) (impact factor: 1.06). 04/2012; 72(10):1081-1090. DOI:10.1134/S0006297907100069

ABSTRACT Low-molecular-weight aldehydes (glyoxal, methylglyoxal, 3-deoxyglucosone) generated on autooxidation of glucose under conditions
of carbonyl stress react much more actively with amino groups of L-lysine and ε-amino groups of lysine residues of apoprotein
B-100 in human blood plasma low density lipoproteins (LDL) than their structural analogs (malonic dialdehyde (MDA), 4-hydroxynonenal)
resulting on free radical oxidation of lipids under conditions of oxidative stress. Glyoxal-modified LDL aggregate in the
incubation medium with a significantly higher rate than LDL modified by MDA, and MDA-modified LDL are markedly more poorly
absorbed by cultured human macrophages and significantly more slowly eliminated from the rat bloodstream upon intravenous
injection. Studies on kinetics of free radical oxidation of rat liver membrane phospholipids have shown that ubiquinol Q10 is the most active lipid-soluble natural antioxidant, and suppression of ubiquinol Q10 biosynthesis by β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitors (statins) is accompanied by intensification of
lipid peroxidation in rat liver biomembranes and in LDL of human blood plasma. Injection of ubiquinone Q10 protects the human blood plasma LDL against oxidation and prevents oxidative stress-induced damages to rat myocardium. A
unified molecular mechanism of atherogenic action of carbonyl-modified LDL in disorders of lipid and carbohydrate metabolism
is discussed.

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    Article: Nutritional improvement of metabolic syndrome parameters in immature fructose-fed wild-type mice.
    J C Cha, V Ivanov, M W Roomi, T Kalinovsky, A Niedzwiecki, M Rath
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    ABSTRACT: The incidence of type 2 diabetes mellitus is on the increase worldwide, with both environmental and genetic factors implicated in its development. Diabetes is often preceded by metabolic syndrome (MS) and may develop in normal adults ingesting a high fructose diet. The effect of high fructose intake on the development of MS in children and adolescents is less clear. Our objective was to study the effects of a nutrient mixture and metformin (MET), a widely used oral diabetic medication, in modulating the physiological and biochemical parameters of a high fructose diet in immature mice. C57BL/6J wild‑type mice aged 7 weeks were administered 12% fructose in their water and MET in distilled water or a diabetic nutrient mix (DNM) over 7 weeks. DNM-fed mice showed a decrease in systolic blood pressure, total cholesterol and fructosamine compared to the fructose-fed only group (p<0.05). A discordant result was observed in the MET group, with a decrease in blood pressure but increases in total cholesterol and fructosamine (p<0.05). Serum glucose did not change significantly among the groups. Thus, symptoms of fructose-induced MS in young mice could be countered nutritionally. Additionally, MET may improve certain biochemical markers while worsening others.
    Molecular Medicine Reports 4(6):1053-9. · 0.42 Impact Factor
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Keywords

active lipid-soluble natural antioxidant
 
amino groups
 
carbohydrate metabolism
 
carbonyl stress
 
carbonyl-modified LDL
 
free radical oxidation
 
Glyoxal-modified LDL aggregate
 
human blood plasma
 
human blood plasma LDL
 
human blood plasma low density lipoproteins
 
Low-molecular-weight aldehydes
 
lysine residues
 
MDA-modified LDL
 
oxidative stress
 
oxidative stress-induced damages
 
rat bloodstream
 
rat liver biomembranes
 
rat liver membrane phospholipids
 
unified molecular mechanism
 
ε-amino groups