The influence of dietary copper on dense granule secretion and cytoskeletal remodeling in thrombin-stimulated rat platelets

Abstract

Cytoskeletal remodeling and dense granule secretion in response to thrombin stimulation were examined in platelets isolated from male weanling rats fed diets containing 0.4, 1.2, 2.0, 2.8 and 5.2 μg Cu/g diet. After five weeks, rats consuming diets containing less than 5.2 μg Cu/g exhibited reduced liver Cu concentrations and plasma ceruloplasmin amine oxidase activity. Anemia, however, was present only in rats consuming diet containing 0.4 μg Cu/g. Cytoskeletal myosin heavy chain (MHC) content in platelets prior to and 45s following activation with 2 nM thrombin tended to increase with decreasing dietary Cu, but significant (P<0.05) differences occurred only between rats fed diets containing 0.4 and 5.2 μg Cu/g. Similarly, when platelet dense granule secretion was assessed by measuring the rate of ATP secretion and the total amount of ATP secreted following stimulation with 2 nM thrombin, significant differences occurred only between rats fed diets containing 0.4 and 5.2 μg Cu/g. Because rats consuming diet containing 0.4 μg Cu/g became anemic, the alteration of platelet responses in these rats may have been a direct result of anemia rather than copper deficiency. However, neither cytoskeletal MHC content nor dense granule secretion were altered in rats with iron deficiency anemia. These results indicate that moderate copper deficiency has little effect on cytoskeletal remodeling and dense granule secretion in thrombin-stimulated platelets and that anemia per se is most likely not a causative factor in the altered platelet responses associated with severe copper deficiency.