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Study of molecular targets influencing homocysteine and cholesterol metabolism in growing rats by manipulation of dietary selenium and methionine concentrations

  • Nicole M. Wolf (a1), Kristin Mueller (a1), Frank Hirche (a1), Erika Most (a2), Josef Pallauf (a2) and Andreas S. Mueller (a1)...
Abstract

Inconsistent results exist from human and animal studies for Se and methionine (Met) regarding their influence on homocysteine (HCys) and cholesterol (Chol) metabolism. To elucidate these contradictions, sixty-four weanling albino rats were divided into eight groups of 8, and were fed diets containing four different Se levels (15, 50, 150 and 450 μg/kg) either in combination with the recommended Met level of 3 g/kg (C15, C50, C150 and C450) or with an increased Met concentration of 15 g/kg (M15, M50, M150 and M450) for 8 weeks. Plasma HCys was twofold higher in the Se-supplemented C groups than in group C15. Met addition also doubled plasma HCys compared with the respective C groups. In contrast, the expression of the key enzymes of glutathione biosynthesis in the liver was significantly lowered by Se and in particular by Met. Liver Chol concentration was significantly higher in all the Se-supplemented C and M groups than in groups C15 and M15. Plasma Chol was, however, lowered. The uninfluenced expression of sterol-regulatory element-binding protein 2 and of hydroxymethyl-glutaryl-CoA reductase, the increased LDL receptor expression and the reduced expression of the hepatobiliary Chol exporter ATP-binding-cassette-transporter 8 (ABCG8) by Se and/or Met explain these findings. We conclude that the elevation of plasma HCys in rats by Se and Met results from a higher export into plasma. The fact that Se in particular combined with Met increases liver Chol but reduces plasma Chol should be addressed in future investigations focussing on the regulation of ABCG8, which is also selectively involved in the reverse transport of phytosterols in the small intestine.

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Corresponding author
*Corresponding author: Andreas S. Mueller, fax +49 345 55 27124, email andreas.mueller@landw.uni-halle.de
References
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1Zhou J & Austin RC (2009) Contributions of hyperhomocysteinemia to atherosclerosis: causal relationship and potential mechanisms. Biofactors 35, 120129.
2Lin CP, Chen YH, Chen JW, et al. (2008) Cholestin (Monascus purpureus rice) inhibits homocysteine-induced reactive oxygen species generation, nuclear factor-kappaB activation, and vascular cell adhesion molecule-1 expression in human aortic endothelial cells. J Biomed Sci 15, 183196.
3Kassab A, Ajmi T, Issaoui M, et al. (2008) Homocysteine enhances LDL fatty acid peroxidation, promoting microalbuminuria in type 2 diabetes. Ann Clin Biochem 45, 476480.
4Séguin C, Abid MR, Spokes KC, et al. (2008) Priming effect of homocysteine on inducible vascular cell adhesion molecule-1 expression in endothelial cells. Biomed Pharmacother 62, 395400.
5Au-Yeung KK, Woo CW, Sung FL, et al. (2004) Hyperhomocysteinemia activates nuclear factor-kappaB in endothelial cells via oxidative stress. Circ Res 94, 2836.
6Ungvari Z, Csiszar A, Edwards JG, et al. (2003) Increased superoxide production in coronary arteries in hyperhomocysteinemia: role of tumor necrosis factor-alpha, NAD(P)H oxidase, and inducible nitric oxide synthase. Arterioscler Thromb Vasc Biol 23, 418424.
7Griffiths HR, Aldred S, Dale C, et al. (2006) Homocysteine from endothelial cells promotes LDL nitration and scavenger receptor uptake. Free Radic Biol Med 40, 488500.
8Flicker L (2009) Life style interventions to reduce the risk of dementia. Maturitas 63, 319322.
9Bønaa KH, Njølstad I, Ueland PM, et al. (2006) Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 354, 15781588.
10Antoniades C, Antonopoulos AS, Tousoulis D, et al. (2009) Homocysteine and coronary atherosclerosis: from folate fortification to the recent clinical trials. Eur Heart J 30, 615.
11Lonn E, Yusuf S, Arnold MJ, et al. (2006) Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 354, 15671577.
12Malinow MR, Bostom AG, Krauss RM, et al. (1999) Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 99, 178182.
13Stanger O, Herrmann W, Pietrzik K, et al. (2003) DACH-LIGA homocystein (German, Austrian and Swiss Homocysteine Society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med 41, 13921403. Review. Erratum in: Clin Chem Lab Med 2004; 42, 113–116.
14Max Rubner-Institut, Bundesforschungsinstitut für Ernährung und Lebensmittel, Haid-und-Neu-Str. 9 76131 [Karlsruhe, editor].
15Must A, Jacques PF, Rogers G, et al. (2003) Serum total homocysteine concentrations in children and adolescents: results from the third National Health and Nutrition Examination Survey (NHANES III). J Nutr 133, 26432649.
16Heinz J, Kropf S, Luley C, et al. (2009) Homocysteine as a risk factor for cardiovascular disease in patients treated by dialysis: a meta-analysis. Am J Kidney Dis 54, 478489.
17Halpin KM & Baker DH (1984) Selenium deficiency and transsulfuration in the chick. J Nutr 114, 606612.
18Uthus EO, Yokoi K & Davis CD (2002) Selenium deficiency in Fisher-344 rats decreases plasma and tissue homocysteine concentrations and alters plasma homocysteine and Cys redox status. J Nutr 132, 11221128.
19Uthus EO, Ross SA & Davis CD (2007) Differential effects of dietary selenium (Se) and folate on methyl metabolism in liver and colon of rats. Biol Trace Elem Res 109, 201214.
20Uthus EO & Ross SA (2007) Dietary selenium affects homocysteine metabolism differently in Fisher-344 rats and CD-1 mice. J Nutr 137, 11321136.
21Uthus EO & Ross SA (2009) Dietary selenium (Se) and copper (Cu) interact to affect homocysteine metabolism in rats. Biol Trace Elem Res 129, 213220.
22González S, Huerta JM, Alvarez-Uría J, et al. (2004) Serum selenium is associated with plasma homocysteine concentrations in elderly humans. J Nutr 134, 17361740.
23Klapcińska B, Poprzęcki S, Danch A, et al. (2005) Selenium levels in blood of upper Silesian population: evidence of suboptimal selenium status in a significant percentage of the population. Biol Trace Elem Res 108, 115.
24Bates CJ, Thane CW, Prentice A, et al. (2002) Selenium status and its correlates in a British national diet and nutrition survey: people aged 65 years and over. J Trace Elem Med Biol 16, 118.
25Bélanger MC, Dewailly E, Berthiaume L, et al. (2006) Dietary contaminants and oxidative stress in Inuit of Nunavik. Metabolism 55, 989995.
26Venn BJ, Grant AM, Thomson CD, et al. (2008) Selenium supplements do not increase plasma total homocysteine concentrations in men and women. J Nutr 133, 418420.
27Bekaert B, Cooper ML, Green FR, et al. (2008) Effect of selenium status and supplementation with high-selenium yeast on plasma homocysteine and B vitamin concentrations in the UK elderly. Mol Nutr Food Res 52, 13241333.
28Hirche F, Schröder A, Knoth B, et al. (2006) Met-induced elevation of plasma homocysteine concentration is associated with an increase of plasma cholesterol in adult rats. Ann Nutr Metab 50, 139146.
29Hirche F, Schröder A, Knoth B, et al. (2006) Effect of dietary Met on plasma and liver cholesterol concentrations in rats and expression of hepatic genes involved in cholesterol metabolism. Br J Nutr 95, 879888.
30Ward M, McNulty H, Pentieva K, et al. (2000) Fluctuations in dietary Met intake do not alter plasma homocysteine concentration in healthy men. J Nutr 130, 26532657.
31Ward M, McNulty H, McPartlin J, et al. (2001) Effect of supplemental Met on plasma homocysteine concentrations in healthy men: a preliminary study. Int J Vitam Nutr Res 71, 8286.
32Verhoef P, van Vliet T, Olthof MR, et al. (2005) A high-protein diet increases postprandial but not fasting plasma total homocysteine concentrations: a dietary controlled, crossover trial in healthy volunteers. Am J Clin Nutr 82, 553558.
33Virtanen JK, Voutilainen S, Rissanen TH, et al. (2006) High dietary Met intake increases the risk of acute coronary events in middle-aged men. Nutr Metab Cardiovasc Dis 16, 1131120.
34Hart SR, Mangoni AA, Swift CG, et al. (2006) Effect of Met loading on pulse wave analysis in elderly volunteers. Postgrad Med J 82, 524527.
35Bleys J, Navas-Acien A, Stranges S, et al. (2008) Serum selenium and serum lipids in US adults. Am J Clin Nutr 88, 416423.
36Stranges S, Laclaustra M, Ji C, et al. (2010) Higher selenium status is associated with adverse blood lipid profile in British adults. J Nutr 140, 8187.
37Reeves PG (1997) Components of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr 127, Suppl. 5, S838S841.
38Mueller AS, Pallauf J & Most E (2002) Parameters of dietary selenium and vitamin E deficiency in growing rabbits. J Trace Elem Med Biol 16, 4755.
39Lawrence RA & Burk RF (1976) Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71, 952958.
40Bradford MM (1976) A rapid sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72, 248254.
41Vester B & Rasmussen K (1991) High performance liquid chromatography method for rapid and accurate determination of homocysteine in plasma and serum. Eur J Clin Chem Clin Biochem 29, 549554.
42Hara A & Radin NS (1978) Lipid extraction of tissues with a low-toxicity solvent. Anal Biochem 90, 420426.
43De Hoff JL, Davidson LM & Kritchevsky D (1978) An enzymatic assay for determining free and total cholesterol in tissue. Clin Chem 24, 433435.
44Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29, e45.
45Mueller AS, Klomann SD, Wolf NM, et al. (2008) Redox regulation of protein Tyr phosphatase 1B by manipulation of dietary selenium affects the triglyceride concentration in rat liver. J Nutr 138, 23282336.
46Mueller AS, Bosse AC, Most E, et al. (2009) Regulation of the insulin antagonistic protein Tyr phosphatase 1B by dietary Se studied in growing rats. J Nutr Biochem 20, 235247.
47Barnes KM, Evenson JK, Raines AM, et al. (2009) Transcript analysis of the selenoproteome indicates that dietary selenium requirements of rats based on selenium-regulated selenoprotein mRNA levels are uniformly less than those based on glutathione peroxidase activity. J Nutr 139, 199206.
48Bosse AC, Pallauf J, Hommel B, et al. (2009) Impact of selenite and selenate on differentially expressed genes in rat liver examined by microarray analysis. Biosci Rep (Epublication ahead of print version 14 Aug 2009).
49Hill KE, Burk RF & Lane JM (1987) Effect of selenium depletion and repletion on plasma glutathione and glutathione-dependent enzymes in the rat. J Nutr 117, 99104.
50Hill KE & Burk RF (1985) Effect of selenium deficiency on the disposition of plasma glutathione. Arch Biochem Biophys 240, 166171.
51Hill KE & Burk RF (1982) Effect of selenium deficiency and vitamin E deficiency on glutathione metabolism in isolated rat hepatocytes. J Biol Chem 257, 1066810672.
52Stead LM, Brosnan ME & Brosnan JT (2000) Characterization of homocysteine metabolism in the rat liver. Biochem J 350, 685692.
53Blom HJ (2000) Consequences of homocysteine export and oxidation in the vascular system. Semin Thromb Hemost 26, 227332.
54Wallace HM & Fraser AV (2004) Inhibitors of polyamine metabolism: review article. Amino Acids 26, 353365.
55Obeid O, Elfakhani M, Hlais S, et al. (2008) Plasma copper, zinc, and selenium levels and correlates with metabolic syndrome components of Lebanese adults. Biol Trace Elem Res 123, 5865.
56Karita K, Yamanouchi Y, Takano T, et al. (2008) Associations of blood selenium and serum lipid levels in Japanese premenopausal and postmenopausal women. Menopause 15, 119124.
57Dhingra S & Bansal MP (2006) Modulation of hypercholesterolemia-induced alterations in apolipoprotein B and HMG-CoA reductase expression by selenium supplementation. Chem Biol Interact 161, 4956.
58Dhingra S & Bansal MP (2005) Hypercholesterolemia and apolipoprotein B expression: regulation by selenium status. Lipids Health Dis 4, 28.
59Dhingra S & Bansal MP (2006) Attenuation of LDL receptor gene expression by selenium deficiency during hypercholesterolemia. Mol Cell Biochem 282, 7582.
60Obeid R & Herrmann W (2009) Homocysteine and lipids: S-adenosyl Met as a key intermediate. FEBS Lett 583, 12151225.
61Zhao Y, Su B, Jacobs RL, et al. (2009) Lack of phosphatidylethanolamine N-methyltransferase alters plasma VLDL phospholipids and attenuates atherosclerosis in mice. Arterioscler Thromb Vasc Biol 29, 13491355.
62Werstuck GH, Lentz SR, Dayal S, et al. (2001) Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways. J Clin Invest 107, 12631273.
63Taniguchi M, Nagao K, Inoue K, et al. (2008) Cholesterol lowering effect of sulfur-containing amino acids added to a soybean protein diet in rats. J Nutr Sci Vitaminol 54, 448453.
64Kawasaki M, Funabiki R & Yagasaki K (1998) Effects of dietary Met and cystine on lipid metabolism in hepatoma-bearing rats with hyperlipidemia. Lipids 33, 905911.
65Yabe D, Brown MS & Goldstein JL (2002) Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins. Proc Natl Acad Sci U S A 99, 1275312758.
66Kidambi S & Patel SB (2008) Cholesterol and non-cholesterol sterol transporters: ABCG5, ABCG8 and NPC1L1: a review. Xenobiotica 38, 11191139.
67Duan LP, Wang HH & Wang DQ (2004) Cholesterol absorption is mainly regulated by the jejunal and ileal ATP-binding cassette sterol efflux transporters Abcg5 and Abcg8 in mice. J Lipid Res 45, 13121323.
68Woo CW, Siow YL, Pierce GN, et al. (2005) Hyperhomocysteinemia induces hepatic cholesterol biosynthesis and lipid accumulation via activation of transcription factors. Am J Physiol Endocrinol Metab 288, 10021010.
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