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Folate protects against oxidative modification of human LDL

Published online by Cambridge University Press:  09 March 2007

Emi Nakano
Affiliation:
Division of Clinical Science, Northern General Hospital, University of Sheffield, Sheffield S5 7AU, UK
John A. Higgins
Affiliation:
Department of Molecular Biology and Biotechnology, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, UK,
Hilary J. Powers*
Affiliation:
Division of Clinical Science, Northern General Hospital, University of Sheffield, Sheffield S5 7AU, UK
*
*Corresponding author: Dr Hilary J. Powers, fax +44 114 261 0112, email [email protected]
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Abstract

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Elevated plasma total homocysteine is considered to be a graded risk factor for cardiovascular disease. Folate, through its homocysteine-lowering potential, may therefore be protective. Folate, however, may have protective effects independent of homocysteine-lowering. We have measured the effects of folate on Cu-catalysed oxidative damage to the unsaturated lipids in human LDL. Experiments were carried out in the presence of citrate, and followed increases in absorption at 234 nm, which measures the amount of conjugated diene produced. There is a lag time during which endogenous antioxidants are oxidised, followed by rapid oxidation of lipid. Addition of 0–6 μM-5-methyltetrahydrofolate produced a dose-dependent increase in the lag time, suggesting that folate may have a direct anti-oxidant role in vivo, which is independent of any indirect effects through lowering of homocysteine levels.

Type
short communication
Copyright
Copyright © The Nutrition Society 2001

References

Referenses

Bellamy, MF, McDowell, IFW, Ramsey, MW, Brownlee, M, Newcombe, RG & Lewis, MJ (1999) Oral folate enhances endothelial function in hyperhomocysteinaemic subjects. European Journal of Clinical Investigation 29, 659662.CrossRefGoogle ScholarPubMed
Bostom, AG, Shemin, D, Bagley, P, Massey, ZA, Zanabli, A, Christopher, K, Spiegel, P, Jacques, PF, Dworkin, L & Selhub, J (2000) Controlled comparison of 1-5-methyltetrahydrofolate versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients. Circulation 101, 28292832.CrossRefGoogle ScholarPubMed
Boushey, CJ, Beresford, SAA, Omenn, GS & Motulsky, AJ (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. American Medical Association 274, 10491057.CrossRefGoogle ScholarPubMed
Buege, JA & Aust, SD (1978) Microsomal lipid peroxidation. Methods in Enzymology 52, 302310.CrossRefGoogle ScholarPubMed
Esterbauer, H, Striegl, G, Puhl, H & Rotheneder, M (1989) Continuous monitoring of in vitro oxidation of human low density lipoprotein. Free Radical Research Communications 6, 6775.CrossRefGoogle ScholarPubMed
Graham, JM, Higgins, JA, Gillott, T, Taylor, T, Wilkinson, J, Ford, T & Billington, D (1996) A novel method for rapid separation of plasma lipoproteins using self-generating gradients of iodixanol. Atherosclerosis 124, 125135.CrossRefGoogle ScholarPubMed
Lobo, A, Naso, A, Arheart, K, Kruger, WD, Abou-Ghazala, T, Alsous, F, Nahlawi, M, Gupta, A, Moustapha, A, van Lente, F, Jacobsen, DW & Robinson, K (1999) Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12. American Journal of Cardiology 83, 821825.CrossRefGoogle ScholarPubMed
McDowell, IFW, McEneny, J & Trimble, ER (1995) A rapid method for measurement of the susceptibility to oxidation of low-density lipoprotein. Annals of Clinical Biochemistry 32, 167174.CrossRefGoogle ScholarPubMed
Nygard, O, Nordrehaug, JE, Refsum, H, Ueland, PM, Farstad, M & Vollset, SE (1997) Plasma homocysteine levels and mortality in patients with coronary artery disease. New England Journal of Medicine 337, 230236.CrossRefGoogle ScholarPubMed
Schnitzer, E, Pinchuk, I, Fainaru, M, Schafer, Z & Lichtenberg, D (1995) Copper-induced lipid oxidation in unfractionated plasma: The lag preceding oxidation as a measure of oxidation resistance. Biochemical and Biophysical Research Communications 216, 854861.CrossRefGoogle ScholarPubMed
Usui, M, Matsuoka, H, Miyazaki, H, Ueda, S, Okuda, S & Imaizumi, T (1999) Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid. Clinical Science 96, 235239.CrossRefGoogle ScholarPubMed
Verhaar, MC, Wever, RMF, Kastelein, JJP, van Dam, T, Koomans, HA & Rabelink, TJ (1998) 5-Methyltetrahydrofolate, the active form of folic acid, restores endothelial function in familial hypercholesterolemia. Circulation 97, 237241.CrossRefGoogle ScholarPubMed
Wilmink, HW, Stroes, ESG, Erkelens, WD, Gerritsen, WB, Wever, R, Banga, J-D & Rabelink, TJ (2000) Influence of folic acid on postprandial endothelial dysfunction. Arteriosclerosis, Thrombosis and Vascular Biology 20, 185188.CrossRefGoogle ScholarPubMed