An Emerging Role of Defective Copper Metabolism in Heart Disease

Copper is an essential trace metal element that significantly affects human physiology and pathology by regulating various important biological processes, including mitochondrial oxidative phosphorylation, iron mobilization, connective tissue crosslinking, antioxidant defense, melanin synthesis, blood clotting, and neuron peptide maturation. Increasing lines of evidence obtained from studies of cell culture, animals, and human genetics have demonstrated that dysregulation of copper metabolism causes heart disease, which is the leading cause of mortality in the US. Defects of copper homeostasis caused by perturbed regulation of copper chaperones or copper transporters or by copper deficiency resulted in various types of heart disease, including cardiac hypertrophy, heart failure, ischemic heart disease, and diabetes mellitus cardiomyopathy. This review aims to provide a timely summary of the effects of defective copper homeostasis on heart disease and discuss potential underlying molecular mechanisms.     

某电缆厂铜尘职业危害的调查研究

为了解含铜粉尘对工人的职业性危害，本文对某电缆厂铜加工车间劳动卫生及职业性危害进行了调查。结果：生产车间空气中粉尘浓度年几何均值为０．７３ｍｇ／ｍ３，空气中铜尘浓度几何均值为０．０２２ｍｇ／ｍ３，空气中粉尘粒径在５ｕｍ以下者占８４．１６％。接尘者除皮肤感觉异常及呼吸道刺激症状较明显外，无其他特殊发现，但血细胞铜、发铜含量及血清溶菌酶等指标与对照组相比有显著差异（Ｐ＜０．０１或０．０５）。作者认为，上述指标除铜蓝蛋白外，可作为铜尘接触者的观察指标。     

MENKES' DISEASE: ARE WE CLOSER TO LEARNING ITS CAUSE?

Abnormalities of metallothionein biosynthesis have been discovered in Menkes' disease, but they do not account for the entire pathophysiology of the disease.     

Effect of beta-carotene supplementation on the concentrations and distribution of carotenoids,vitamin E,vitamin A,and cholesterol in plasma lipoprotein and non-lipoprotein fractions in healthy older women.

We studied the effect of beta-carotene supplementation on the concentrations and distribution in plasma lipoprotein and non-lipoprotein fractions of carotenoids, alpha-tocopherol, retinol, and cholesterol.

Ten women ingested either 90 mg of beta-carotene or placebo daily for 3 weeks while residing in their homes and eating their usual meals. Carotenoids (beta-carotene, lycopene, lutein/zeaxanthin), retinol, alpha-tocopherol, and cholesterol were measured in plasma lipoprotein and non-lipoprotein fractions before and after treatment.

In the beta-carotene-supplemented group, total plasma beta-carotene increased 14-fold from 0.48 +/? 0.13 to 6.83 +/? 2.12 mumol/L (p = 0.04). Although the greatest increase in beta-carotene was in low-density-lipoproteins (LDL), the magnitude of increase was similar in LDL, high-density-lipoproteins (HDL), and very-low-density-lipoproteins (VLDL). Thus, the relative distribution of beta-carotene in lipoproteins was unchanged: approximately 71% was in LDL, approximately 15% in HDL and approximately 12% in VLDL, before and after beta-carotene supplementation. There were no changes in amounts and distribution in lipoproteins of the other carotenoids, alpha-tocopherol, and cholesterol. There was no change in the amount of retinol in lipoprotein-deficient plasma. There were no changes in total plasma triglycerides. Significant positive correlations were found between LDL- or VLDL-cholesterol and alpha-tocopherol in LDL or VLDL, respectively; between LDL- or VLDL-cholesterol and lutein/zeaxanthin in LDL or VLDL, respectively; and between HDL-cholesterol and beta-carotene in HDL.

beta-Carotene supplementation (90 mg/day for 3 weeks) in healthy older women results in an enrichment of all plasma lipoprotein fractions with beta-carotene, but does not alter the relative distribution of beta-carotene in lipoproteins. beta-Carotene supplementation has no effect on the amounts and relative distribution of lycopene, lutein/zeaxanthin, and alpha-tocopherol in lipoproteins, or of retinol in the non-lipoprotein fraction of plasma. Short-term beta-carotene supplementation has no effect on the concentrations of plasma total triglycerides, total cholesterol, HDL-, LDL-, and VLDL-cholesterol.     

锌、铜对大鼠血脂水平影响的研究

用雄性断乳ｗｉｓｔａｒ大鼠研究了不同水平锌、铜对大鼠血脂水平的影响。结果显示：绝对或相对铜缺乏均引起血清胆固醇、甘油三酯浓度升高；而绝对或相对锌缺乏则主要引起高密度脂蛋白胆固醇（ＨＤＬ－Ｃ）和ＨＤＬ＿２－Ｃ浓度下降。相关分析表明：血清锌与ＨＤＬ－Ｃ、ＨＤＬ＿２－Ｃ呈明显正相关；血清铜与血清胆固醇、甘油三酯呈显著负相关。病理检查显示：除对照组外，其它各组主动脉组织形态均发生不同程度的病理改变，尤以高锌低铜、高铜低锌及低锌低铜组为著。提示在保持适宜铜水平的前提下，补充适量的锌以提高血清ＨＤＬ－Ｃ水平，可预防或延缓高脂血症的发生。     

冠心病人血液微量元素锰、铬、铜、锌的分析

本实验用电感耦合等离子体发射光谱仪测定了33名正常人和63名冠心病人,(急性心肌梗塞25人,陈旧性心肌梗塞29人,慢性冠心病患者9人)血液中微量元素Mn、Cr、Cu、Zn的含量。发现1.对照组血清Mn为0.02145±0.0107ppm;Cr为0.0230±0.0167ppm;Cu为0.905±0.278ppm;Zn为0.0230±0.404ppm;Cu/Zn比值为0.973±0.395。与冠心病组血清Mn、Cr无明显差异。2.不同发作天数的急性心肌梗塞患者血清Cu、Zn和Cu/Zn比值的动态比较,结果表明,在急性心肌梗塞发作时可出现一过性的血清Cu升高,Zn降低,Cu/Zn比值高于对照组,随时间推移铜锌比值逐渐下降。3.陈旧性心肌梗塞和慢性冠心病者血清Cu、Zn和Cu/Zn比值远较对照组低,Cu/Zn比值<0.6的百分比远较对照组多(P<0.01),说明Cu/Zn比值降低可能是冠心病易患因素。4.用Feisher判别法将血清铜锌比值和其它主要易患因素作了横向比较,证明铜锌比值下降是冠心病主要易患因素,并结合国内外资料作了初步探讨。     

SEX DIFFERENCES IN THE SURVIVAL OF COPPER-DEFICIENT RATS

Male rats fed fructose-based, low-copper diets show 100 percent mortality, cardiac hypertrophy, and anemia under conditions where female rats fed the same diet are unaffected.     

Opioid Peptides,Adrenocorticotrophic Hormone and Dietary Copper Intake in Humans

Copper plays an important role in cardiac and brain function possibly through endocrine and neuroendocrine systems. The syndrome of copper deficiency is worsened by dietary fructose and other trace metals such as zinc. We investigated the effect of a low copper diet on plasma opioid peptides in 11 healthy young volunteers who were fed foods low in copper but adequate in all other nutrients. The study was divided into three dietary periods. Copper was added to the diet so that the diet contained 0.66 mg/day for 24 days (marginal Cu), 0.38 mg/day for 42 days (low Cu) and 2.49 mg/day for 24 days (adequate Cu). The indices of copper status, ceruloplasmin and plasma copper concentrations, declined and were significantly lower (p < 0.05) at the end of the low Cu period than at the beginning of the study and the end of the marginal Cu period. They increased significantly at the end of the adequate Cu diet to the levels of the marginal Cu diet. Plasma β-endorphin (BEN), Leu-enkephalin (LE), Met-enkephalin (ME) and Adrenocorticotropic hormone (ACTH) were measured by radioimmunoassay at the beginning of the study and at the end of each dietary period. No significant differences were observed in BEN, LE or ME during any of the periods. There were only small increases in LE and ME at the end of marginal and low copper diet periods and no significant changes were observed on copper repletion. Plasma ACTH was significantly lower at the end of low copper compared to baseline value but was not lower after marginal copper. Copper repletion had no significant effect on ACTH. The data show that plasma opioid peptides did not respond significantly to differential copper intake.     

徐州地区78种常用食物中锌、铜、铁的含量及其意义

<正> 近年来缺锌缺铁的报告屡有发表,微营养缺乏的问题已经引起广泛的关注。调查发现徐州市少年儿童血清锌水平较低,血清铜含量较高;徐州市居民从饮水中获取的锌、铁、铜等微量元素极少。又鉴于徐州地区为铁锌性土壤,我们于1986年对徐州地区常用主要食物中锌、铜、铁的含量进行了测定和研究。     

5-Br-DMPAP直接光度法测定血清铜

目的 :建立一种快速、简便、灵敏分光光度法测定血清铜 ;方法 :在表面活性剂 Triton X-1 0 0存在下 ,用 2 - ( 5 -溴 - 2 -吡啶偶氮 ) - 5 -二甲氨基酚 (简称 5 - Br- DMPAP)作显色剂直接光度法测定血清铜 ;结果 :该方法测定血清铜 ,显色络合物最大吸收波长为 5 60 nm,线性范围达 63.0 μ mol· L-1,表观摩尔吸光数为 5 .89× 1 0 4 L·mol-1·cm-1。回收率为 98.8%～1 0 1 .5 % ,变异系数 ( CV) 2 .3% ,与原子吸收分光光度法比较相关良好 ,Y=0 .95 5 X+ 0 .833,r=0 .9663,P>0 .0 5 ,36例健康人血清铜含量为 1 0 .0～ 2 3.6μmol· L-1( x± 2 s) ;结论 :该法血清用量少 ,不必去蛋白 ,具有操作快速、简便、结果灵敏可靠等优点 ,适合临床应用     

饲料蛋白质水平对大鼠蛋白质、锌、铁和铜吸收利用的影响

Ｗｉｓｔａｒ纯品系断奶雄性大鼠３２只，随机分成４组，喂纯合成饲料。第１、２、３、４组饲料含蛋白质分别为５％、１０％、２０％和１０％，其它成份相同，第５０天只有第４组改喂以无氮饲科并与其它三组同样收集５天粪、尿，测定氮及锌、铁、铜的代谢量，第５６天处死大鼠，测毛和肝、肾、脑、睾丸、胫骨中锌、铁、铜的含量。结果表明：低蛋白质水平组影响大鼠体重增长和蛋白质代谢，机体组织锌、铁，铜含量降低，经粪便排出锌、铁量增加，锌和铁的吸收与存留显著降低。本文还对蛋白质营养水平不同所致的锌、铁、铜营养状况缺乏时毛中锌、铁、铜含量作为诊断指标的意义进行了探讨。     

铁、铜对过量锌饲养小鸡生物效应的影响

本文对饲料中过量锌对小鸡铁,铜利用的影响以及补充适量铜或铁、铜的预防效果进行了研究。一日龄雄性小鸡喂基础饲料5天后按体重分成4组,用铁锌铜含量不同的实验饲料喂养28天,观察小鸡生长情况及血液生化指标。结果表明,高锌组小鸡生长不良,Hb下降13％,RBC,Hct,MCV均降低、FEP增加,呈现典型小细胞低色素贫血态,血液及肝肾中锌含量增加,铁和铜含量减少;红细胞超氧化物岐化酶和血浆铜兰蛋白活性下降。在含锌饲料中补充铜能改善小鸡的生长状况,体内铜水平及铜依赖酶活性,对改善贫血及体内铁水平的作用不明显。同时补铁则小鸡各项实验指标均得到明显改善。     

缺铜致大鼠高脂血症的研究

雄性断奶大鼠,随机分为两组,喂合铜饲料和缺铜饲料,饲养一个月。缺铜组大鼠体重增加少,血浆总蛋白和血红蛋白含量降低,血浆铜和动脉壁铜含量下降,同时出现血脂增高和单胺氧化酶活力降低。实验结果表明,食物缺铜可引起高胆固醇血症和含铜酶活力降低。     

A requirement for copper in angiogenesis

Although two decades have passed since copper was shown to stimulate blood vessel formation in the avascular cornea of rabbits, only recently have clinical trials established that Cu privation by diet or by Cu chelators diminishes a tumor's ability to mount an angiogenic response. These data have shed new light on the functional role of Cu in microvessel development and, of equal importance, stimulated new nutritional models of cancer therapeutic intervention.     

健康人血清铜测定

健康人血清铜测定俞锡林，鲁金瑞，潘存，蒋挺英（浙江医科大学附属儿童医院，杭州３１０００３）关键词：健康人，血清铜ＭｅａｓｕｒｅｍｅｎｔｏｆＳｅｒｕｍＣｏｐｐｃｒＣｏｎｃｅｎｔｒａｔｉｏｎｉｎＨｅａｌｔｈｙＳｕｂｊｅｃｔｓ￥ＹｕＸｉｌｉｎ；ＬｕＪｉｎｒ...     

COPPER DEFICIENCY AND HYPERCHOLESTEROLEMIA

Increased plasma HDL, rich in apoE, induced by a copper-deficient diet, is associated with decreased hepatic lipoprotein-binding activity in rats.     

矽肺患者血清微量元素探讨

本文选择矽肺及其合并症患者为研究对象,分析了113例血样,6种微量元素。矽肺及其合并症患者血清铜含量和铜、锌比值均有明显升高,矽肺合并症患者血清锌明显降低。初步揭示了该病铜、锌元素变化现律。     

Quantitative genetic analysis of brain copper and zinc in BXD recombinant inbred mice

Abstract

Copper and zinc are trace nutrients essential for normal brain function, yet an excess of these elements can be toxic. It is important therefore that these metals be closely regulated. We recently conducted a quantitative trait loci (QTL) analysis to identify chromosomal regions in the mouse containing possible regulatory genes. The animals came from 15 strains of the BXD/Ty recombinant inbred (RI) strain panel and the brain regions analyzed were frontal cortex, caudate-putamen, nucleus accumbens and ventral midbrain. Several QTL were identified for copper and/or zinc, most notably on chromosomes 1, 8, 16 and 17. Genetic correlational analysis also revealed associations between these metals and dopamine, cocaine responses, saccharine preference, immune response and seizure susceptibility. Notably, the QTL on chromosome 17 is also associated with seizure susceptibility and contains the histocompatibility H2 complex. This work shows that regulation of zinc and copper is under polygenic influence and is intimately related to CNS function. Future work will reveal genes underlying the QTL and how they interact with other genes and the environment. More importantly, revelation of the genetic underpinnings of copper and zinc brain homeostasis will aid our understanding of neurological diseases that are related to copper and zinc imbalance.     

镉致贫血及铁、锌、铜的预防作用

本文探讨了饲镉小鸡发生贫血的性质、原因及补充铁、锌、铜的预防作用。将1日龄雄性京白鸡依体重随机分为6组:对照组、饲镉组、补铁组、补锌组、补铜组及同时补充铁,锌,铜组。实验3周后,测定血红蛋白、红细胞压积、红细胞计数、红细胞脆性、红细胞形态、红细胞游离原卟啉、血浆铜蓝蛋白及肝脏中各元素的浓度。结果表明:1.饲镉小鸡发生了正细胞低色素性贫血,其原因与镉致红细胞变形、渗透脆性增大及机体缺铁、缺铜有关;2.补充铁或铜预防了镉致贫血,补充锌无预防作用;3.饲镉小鸡产生了生长阻滞,补充铁、锌或铜有预防作用。