|Ross, Sharon - NATIONAL CANCER INSTITUTE|
Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: November 15, 2007
Publication Date: April 15, 2008
Repository URL: http://www.fasebj.org
Citation: Uthus, E.O., Ross, S.A. 2008. Dietary selenium (Se) and copper (Cu) interact to affect homocysteine metabolism in rats [Abstract]. Journal of Federation of American Societies for Experimental Biology. 22:696.3. Technical Abstract: Previously we reported that both Se deficiency (SeD) and Cu deficiency (CuD) decreased plasma homocysteine (pHcys) and increased plasma glutathione (pGSH) in rats. We also showed that the catalytic subunit of glutamate-cysteine ligase (Gclc), which catalyzes the rate limiting step in glutathione biosynthesis, was upregulated in SeD as well as in CuD. We suggested that in both deficiencies, that Hcys was being shunted through the transsulfuration pathway as a result of this upregulation. Because both SeD and CuD have similar effects, we hypothesized that a combined deficiency would exacerbate the decrease in pHcys and the increase in pGSH by further upregulating Gclc. In a 2 x 2 experiment, male weanling Sprague-Dawley rats (N=8-10/group) were fed an amino acid-based diet containing either 0 or 0.2 µg Se (as selenite)/g and <1 or 6 µg Cu (as Cu carbonate)/g for 5 wk. Values in the table are means±SD. Both SeD and CuD resulted in decreased pHcys; however, CuD in rats fed 0.2 µg Se/g resulted in a greater decrease in pHcys than did CuD in the SeD rats. SeD and CuD resulted in increased pGSH and the combined deficiencies further exacerbated the increase. Plasma cysteine (pCys) was decreased by SeD and increased by CuD. 0Se <1Cu 0.2Se <1Cu 0Se 6Cu 0.2Se 6Cu p values (Se,Cu,Se x Cu) pHcys, 1.6±0.4a 4.4±0.6b 2.3±0.4a 6.2±1.3c 0.0001, 0.0001, 0.04 pGSH 22±4a 15±3b 12±1bc 10±1c 0.0001, 0.0001, 0.04 pCys 100±8 178±21 89±8 161±24 0.0001, 0.03, 0.65 Bdy wt 162±19 166±24 212±12 230±13 0.1, 0.0001, 0.28 Hrt/Bdy 0.7±0.2 0.7±0.1 0.34±0.02 0.35±0.01 0.67, 0.0001, 0.47 The findings show that a combined deficiency of both Se and Cu results in lower pHcys and significantly elevated pGSH most likely as a result of increased GSH biosynthesis subsequent to upregulation of Gclc.