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This Article Full Text Full Text (PDF) All Versions of this Article: 289/1/H78    most recent 01093.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Dong, F. Articles by Saari, J. T. Search for Related Content PubMed PubMed Citation Articles by Dong, F. Articles by Saari, J. T.

Increased contractility of cardiomyocytes from copper-deficient rats is associated with upregulation of cardiac IGF-I receptor

¹Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming; ²Department of Pharmacology, Physiology and Therapeutics, School of Medicine, University of North Dakota; and ³United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota

Submitted 26 October 2004 ; accepted in final form 18 February 2005

Hearts from severely Cu-deficient rats show a variety of pathological defects, including hypertrophy and, in intact hearts, depression of contractile function. Paradoxically, isolated cardiomyocytes from these rats exhibit enhanced contractile properties. Because hypertrophy and enhanced contractility observed with other pathologies are associated with elevation of insulin-like growth factor-I (IGF)-I, this mechanism was examined for the case of dietary Cu deficiency. Male, weanling Sprague-Dawley rats were provided diets that were deficient (0.5 mg Cu/kg diet) or adequate (6 mg Cu/kg diet) in Cu for 5 wk. IGF-I was measured in serum and hearts by an ELISA method, cardiac IGF-I and IGF-II receptors and IGFBP-3 were measured by Western blotting analysis, and mRNAs for cardiac IGF-I and IGF-II were measured by RT-PCR. Contractility of isolated cardiomyocytes was assessed by a video-based edge-detection system. Cu deficiency depressed serum and heart IGF-I and heart IGFBP-3 protein levels and increased cardiac IGF-I receptor protein. Cardiac IGF-II protein and mRNA for cardiac IGF-I and IGF-II were unaffected by Cu deficiency. A Cu deficiency-induced increase in cardiomyocyte contractility, as indicated by increases in maximal velocities of shortening (–dL/dt) and relengthening (+dL/dt) and decrease in time to peak shortening (TPS), was confirmed. These changes were largely inhibited by use of H-1356, an IGF-I receptor blocker. We conclude that enhanced sensitivity to IGF-I, as indicated by an increase in IGF-I receptor protein, accounts for the increased contractility of Cu-deficient cardiomyocytes and may presage cardiac failure.

insulin-like growth factor-I