Aorta protein expression in marginal and acute zinc deficiency

Abstract
Abstract Human zinc deficiency is a global problem and has a very significant direct impact on health. Until recently, attention has focused on the primary manifestations of zinc deficiency such as impaired growth and immune function. The role that zinc nutrition plays in the development of chronic diseases has barely been considered. The objective of this study was to determine how zinc deficiency can affect protein expression in vascular tissue, and whether the changes observed are likely to pre-dispose the vasculature to pro-atherogenic influences. In 2 separate studies, rats were given semi-synthetic diets which were acutely (<1 mg Zn/kg) or marginally (6 mg Zn/kg) deficient in zinc. Both studies included zinc adequate controls (35 mg Zn/kg) and the acute deficiency study included a pair-fed group. After 39 and 43 days on the acute and marginal diets, respectively, proteins from thoracic aorta were extracted and separated by isoelectric focusing and polyacrylamide gel electrophoresis. Coomassie blue stained protein spots which showed deficiency-related changes in expression were identified by t-tests and principal component analysis. Multiple correlations of affected proteins indicated protein clusters of related function, all either increased or decreased by zinc deficiency. The major clusters of proteins which were decreased in acute and marginal deficiency were related to fatty acid and carbohydrate metabolism. Structurally-related proteins were both increased and decreased, particularly by acute deficiency but also in marginal deficiency. Key fatty acid metabolism proteins included acetyl CoA dehydrogenase, 2-enoyl CoA hydratase and hydroxyacyl CoA dehydrogenase whereas carbohydrate metabolism proteins included glycerol-3-phosphate dehydrogenase, fumarate hydratase and citrate synthase. Key structural proteins included zyxin, transgelins and vimentin. Over 9 transgelin proteins were identified by tandem mass spectrometry and 2D gel western blotting, most of which were increased or decrease by zinc deficiency, and none of which appeared to be phosphorylated. Proteomic data showed that PKC binding protein was increased by acute zinc deficiency but 1D gel western blotting demonstrated a significant deficiency-related decrease in PKCα. In conclusion, both marginal and acute zinc deficiency significantly influenced energy metabolism and structural proteins which may modulate the response of vascular tissue to pro-atherogenic stress.
Year
2008
Category
Refereed journal
Output Tags
SG 2006-2011 WP 4.3 Vascular Health