|Dong, Feng - UNIV OF WYOMING|
|Esberg, Lucy - UNIV OF NORTH DAKOTA|
|Ren, Jun - UNIV OF WYOMING|
Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: December 1, 2004
Publication Date: March 7, 2005
Citation: Saari, J.T., Dong, F., Esberg, L.B., Roughead, Z.K., Ren, J. 2005. Increased contractility is associated with increased cardiac IGF-I receptor protein in copper-deficient cardiomyocytes [abstract]. The Federation of American Societies for Experimental Biology Journal. 19(5):A1486. Technical Abstract: Hearts from copper (Cu)-deficient rats show widespread pathology, including hypertrophy and, in intact hearts, depressed contractile function. Paradoxically, isolated cardiomyocytes from such rats exhibit enhanced contractility. Because hypertrophy and enhanced contractility in other cardiomyopathies are associated with elevated IGF-I, this mechanism was examined for dietary Cu deficiency. Young male rats were fed diets deficient (~0.5 ppm Cu) or adequate (~6 ppm Cu) in Cu for 5 weeks. We measured IGF-I in serum and heart by ELISA, cardiac IGF-I and IGF-II receptors and IGFBP-3 by Western blotting, and mRNAs for cardiac IGF-I and IGF-II by RT-PCR. Contractility of isolated cardiomyocytes was assessed by video-based edge detection. Cu deficiency reduced serum and heart IGF-I and heart IGFBP-3 proteins 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 was confirmed by increases in maximal velocities of shortening (-dL/dt) and re-lengthening (+dL/dt) and a decrease in time to peak shortening (TPS). 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, explains the increased contractility of Cu-deficient cardiomyocytes.