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ARS Home » Plains Area » Grand Forks, North Dakota » Grand Forks Human Nutrition Research Center » Healthy Body Weight Research » Research » Publications at this Location » Publication #156516
Title: ENHANCED ENDOTHELIAL AND INDUCIBLE OXIDE SYNTHASE (NOS) PROTEIN EXPRESSION IS ASSOCIATED WITH ELEVATED NOS ACTIVITY AND NFKAPPAB ACTIVATION IN HEARTS FROM COPPER-DEFICIENT RATS

Author
item Saari, Jack
item DUAN, JINHONG - UNIV OF NORTH DAKOTA
item WOLD, LOREN - UNIV OF NORTH DAKOTA
item LENTSCH, ALEX - UNIV OF LOUISVILLE
item SCHUSCHKE, DALE - UNIV OF LOUISVILLE
item REN, JUN - UNIV OF NORTH DAKOTA

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 12/1/2003
Publication Date: 3/24/2004
Citation: Saari, J.T., Duan, J., Wold, L.E., Lentsch, A.B., Schuschke, D.A., Ren, J. 2004. Enhanced endothelial and inducible oxide synthase (nos) protein expression is associated with elevated nos activity and nfkappab activation in hearts from copper-deficient rats [abstract]. Federation of American Societies for Experimental Biology Journal. 18:A914.

Interpretive Summary:

Technical Abstract: Dietary copper (Cu) deficiency leads to cardiac hypertrophy, fibrosis, derangement of myofibrils and impaired cardiac contractile and electrophysiological function. However, the mechanism responsible for Cu deficiency-induced cardiac dysfunction has not been elucidated. Because prior work has implicated altered nitric oxide (NO) metabolism in this mechanism, we have examined this pathway in further detail. Male 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 (eNOS) and inducible nitric oxide synthase (iNOS) protein expression, 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. NFkappaB is a known transcription factor for iNOS and may also influence the eNOS gene. Activation of NFkappaB, 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 delineate a pathway for enhanced NO production in Cu-deficient hearts and suggest a mechanism for altered cardiac function under dietary Cu deficiency. Supported in part by NIH DK055030.