Cardiac nitric oxide synthases are elevated in dietary copper deficiency.
Cardiac nitric oxide synthases are elevated in dietary copper deficiency.
复制标题
DOI：
10.1016/j.jnutbio.2006.07.006
复制
发表时间：
2007-07
期刊：
影响因子：
--
通讯作者：
J. Saari;L. Wold;J. Duan;Jun Ren;H. Carlson;A. Bode;A. Lentsch;Huawei Zeng;D. Schuschke
中科院分区：
文献类型：
--
作者：
J. Saari;L. Wold;J. Duan;Jun Ren;H. Carlson;A. Bode;A. Lentsch;Huawei Zeng;D. Schuschke
膳食铜（Cu）缺乏导致心脏形态和功能缺陷，提示心力衰竭。然而，同时发生的细胞保护事件也似乎发生。铜缺乏导致心脏功能复杂改变的分子机制尚未阐明。由于先前的工作已经涉及改变一氧化氮（NO）代谢在这一改变的功能，我们已经检查了这一途径的进一步详细。给雄性Sprague-Dawley大鼠喂食铜充足（6 mg Cu/kg饮食）或铜缺乏（<0.5 mg Cu/kg饮食）的饮食5周。内皮型一氧化氮合酶（NOS）和诱导型一氧化氮合酶（iNOS）的蛋白表达，通过蛋白质印迹分析测定，分别高58%和40%，在铜缺乏比铜充足的大鼠心脏。通过将3 H-精氨酸转化为3 H-瓜氨酸测定心脏NOS活性，铜缺乏大鼠比铜充足大鼠高130%。NFκB是一种已知的iNOS转录因子。通过ELISA检测p65亚基，发现铜缺乏大鼠的NFκB活化比铜充足大鼠高33%。再加上先前的证据表明，心脏硝酸盐/亚硝酸盐的生产在铜缺乏的大鼠，这些数据表明，多个途径增强NO的生产，可能有助于改变饮食铜缺乏下的心脏功能。
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 of3H-arginine to3H-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.