Cardiac nitric oxide synthases are elevated in dietary copper deficiency

Jack T. Saari, Loren E. Wold, Jinhong Duan, Jun Ren, Hanqian L. Carlson, Ann M. Bode, Alex B. Lentsch, Huawei Zeng, Dale A. Schuschke

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9 Scopus citations


Dietary copper (Cu) deficiency leads to cardiac morphological and functional defects suggestive of heart failure. However, simultaneous cytoprotective events also appear to occur. The molecular mechanisms responsible for this complex alteration of cardiac function by Cu deficiency have not been elucidated. Because prior work has implicated altered nitric oxide (NO) metabolism in this altered function, we have examined this pathway in further detail. Male Sprague-Dawley rats were fed diets that were either Cu adequate (6 mg Cu/kg diet) or Cu deficient (<0.5 mg Cu/kg diet) for 5 weeks. Endothelial NO synthase (NOS) and inducible NOS (iNOS) protein expressions, as measured by Western blot analysis, were 58% and 40% higher, respectively, in Cu-deficient than in Cu-adequate rat hearts. Cardiac NOS activity, as measured by conversion of 3H-arginine to 3H-citrulline, was 130% higher in Cu-deficient than in Cu-adequate rats. NFκB is a known transcription factor for iNOS. Activation of NFκB, determined by an ELISA for the p65 subunit, was found to be 33% higher in Cu-deficient than in Cu-adequate rats. Coupled with prior evidence of elevated cardiac nitrate/nitrite production in Cu-deficient rats, these data suggest multiple pathways for enhanced NO production that may contribute to altered cardiac function under dietary Cu deficiency.

Original languageEnglish (US)
Pages (from-to)443-448
Number of pages6
JournalJournal of Nutritional Biochemistry
Issue number7
StatePublished - Jul 2007

Bibliographical note

Funding Information:
This study was funded in part by the American Diabetes Association (7-0-RA-21 to J. Ren) and the National Institutes of Health (DK055030 to D. Schuschke).


  • Copper deficiency
  • Heart
  • NFκB
  • Nitric oxide synthase
  • eNOS
  • iNOS


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