Copper and signal transduction: Platelets as a model to determine the role of copper in stimulus‐response coupling

Article type: Research Article

Authors: Johnson, W. Thomas^;

Affiliations: United States Department of Agriculture, Agricultural Research Service**, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202‐9034, USA

Note: [] Corresponding Author: W. Thomas Johnson, Ph.D., USDA, ARS, Grand Forks Human Nutrition Research Center, P.O. Box 9034, Grand Forks, North Dakota 58202‐9034, USA. Tel.: +1 701 795 8411; Fax: +1 701 795 8220; E‐mail: tjohnson@ gfhnrc.ars.usda.gov.

Abstract: Platelets from copper‐deficient rats have been used as a model to investigate the role of copper in receptor‐mediated cellular responses. Copper deficiency doubles the rate of dense granule secretion and increases myosin association with the platelet cytoskeleton following thrombin stimulation. Mechanisms underlying the effects of copper deficiency on thrombin‐ induced signals that elicit dense granule secretion involve suppression of protein kinase C activity and impairment of Ca^{2+} release from intracellular stores. Copper deficiency also reduces the cellular GTP content of platelets. This may limit receptor effector coupling through GTP‐dependent regulatory proteins leading to protein kinase C activation and the release of Ca^{2+} from intracellular stores. The reduction in GTP content during copper deficiency results from its utilization to maintain cellular ATP levels in response to severely inhibited cytochrome c oxidase activity in platelet mitochondria. Thus, the role of copper in maintaining normal signal transduction may be indirectly related to its biological function in mitochondria.

Journal: Biofactors, vol. 10, no. 1, pp. 53-59, 1999