锌对Caco2细胞ZIP4 mRNA表达的影响

目的研究锌对Caco2细胞ZIP4mRNA表达的影响及其规律。方法通过锌特异螯合剂TPEN建立低锌Caco2细胞模型,RT-PCR法获得ZIP4cDNA片断,10μmol/LTPEN培养基诱导后,分别检测0、2、4、6、8和10h时点ZIP4mRNA的表达,及0、2·5、5、7·5、10μmol/LTPEN培养基诱导6h,检测各浓度组ZIP4mRNA的表达。结果RT-PCR获得单一条带的片断,大小与设计一致,获得正确的ZIP4cDNA片断,随着低锌时间的增加,ZIP4mRNA表达也升高,6h达到峰值;随着TPEN浓度的升高,ZIP4mRNA表达也随之升高。结论ZIP4mRNA表达受锌的调控,提示可能参与小肠对锌的吸收。     

Zinc Fortification Decreases ZIP1 Gene Expression of Some Adolescent Females with Appropriate Plasma Zinc Levels

Zinc homeostasis is achieved after intake variation by changes in the expression levels of zinc transporters. The aim of this study was to evaluate dietary intake (by 24-h recall), absorption, plasma zinc (by absorption spectrophotometry) and the expression levels (by quantitative PCR), of the transporters ZIP1 (zinc importer) and ZnT1 (zinc exporter) in peripheral white blood cells from 24 adolescent girls before and after drinking zinc-fortified milk for 27 day. Zinc intake increased (p < 0.001) from 10.5 ± 3.9 mg/day to 17.6 ± 4.4 mg/day, and its estimated absorption from 3.1 ± 1.2 to 5.3 ± 1.3 mg/day. Mean plasma zinc concentration remained unchanged (p > 0.05) near 150 µg/dL, but increased by 31 µg/dL (p < 0.05) for 6/24 adolescents (group A) and decreased by 25 µg/dL (p < 0.05) for other 6/24 adolescents (group B). Expression of ZIP1 in blood leukocytes was reduced 1.4-fold (p < 0.006) in group A, while for the expression of ZnT1 there was no difference after intervention (p = 0.39). An increase of dietary zinc after 27-days consumption of fortified-milk did not increase (p > 0.05) the plasma level of adolescent girls but for 6/24 participants from group A in spite of the formerly appropriation, which cellular zinc uptake decreased as assessed by reduction of the expression of ZIP1.     

Zinc: mechanisms of host defense

Zinc deficiency in humans decreases the activity of serum thymulin (a thymic hormone), which is required for maturation of T-helper cells. T-helper 1 (Th(1)) cytokines are decreased but T-helper 2 (Th(2)) cytokines are not affected by zinc deficiency in humans. This shift of Th(1) to Th(2) function results in cell-mediated immune dysfunction. Because IL-2 production (Th(1) cytokine) is decreased, this leads to decreased activities of natural-killer cell and T cytolytic cells, which are involved in killing viruses, bacteria, and tumor cells. In humans, zinc deficiency may decrease the generation of new CD4+ T cells from the thymus. In cell culture studies (HUT-78, a Th(0) human malignant lymphoblastoid cell line), as a result of zinc deficiency, nuclear factor-kappaB (NF-kappaB) activation, phosphorylation of IkappaB, and binding of NF-kappaB to DNA are decreased and this results in decreased Th(1) cytokine production. In another study, zinc supplementation to humans decreased the gene expression and production of pro-inflammatory cytokines and decreased oxidative stress markers. In HL-60 cells (a human pro-myelocytic leukemia cell line), zinc deficiency increased the levels of TNF-alpha, IL-1beta, and IL-8 cytokines and mRNA. In these cells, zinc induced A20, a zinc finger protein that inhibited NF-kappaB activation via tumor necrosis factor receptor associated factor pathway, and this decreased gene expression of pro-inflammatory cytokines and oxidative stress markers. We conclude that zinc has an important role in cell-mediated immune functions and also functions as antiinflammatory and antioxidant agent.     

Changes in dietary zinc and copper affect zinc-status indicators of postmenopausal women, notably, extracellular superoxide dismutase and amyloid precursor proteins

BACKGROUND: Zinc is an essential trace element for human health and well-being; however, methods currently available for the assessment of zinc status in humans are unsatisfactory. OBJECTIVE: The objective was to critically evaluate the use of various indicators of zinc status in humans in a controlled metabolic ward study. DESIGN: Indicators of zinc status were measured in 25 healthy postmenopausal women aged 64.9 +/- 6.7 y. After a 10-d equilibration period, volunteers consumed a diet with either a low (1 mg/d; n = 12) or a high (3 mg/d; n = 13) copper content based on a total energy content of 8.4 MJ. They received the same amount of copper throughout the study. Both groups were fed the basal diet (3 mg Zn/d) with no zinc supplement for one 90-d period, and the diet supplemented with 50 mg Zn/d for another 90-d period. RESULTS: Zinc supplementation significantly increased (P < 0.0001) extracellular but not erythrocyte superoxide dismutase activity. This increase was more apparent when subjects were fed the low-copper diet. Zinc supplementation in combination with the low-copper diet significantly decreased (P < 0.01) amyloid precursor protein expression in platelets. Other indicators of zinc status that were significantly elevated after zinc supplementation were as follows: plasma zinc and free thyroxine concentrations and mononuclear 5'-nucleotidase activity. CONCLUSION: The measurement of serum extracellular superoxide dismutase activity may be useful as a marker for the functional assessment of zinc status in humans.     

锌及ZIP家族与前列腺癌关系的研究进展

锌是人体中一种重要的微量元素，人体前列腺上皮细胞具有聚集高浓度锌离子的功能，锌在维持正常前列腺功能和前列腺恶性肿瘤发生发展过程中均起着十分重要的作用。前列腺癌组织中锌含量显著低于正常前列腺，但其锌减低机制目前尚不清楚，可能与前列腺上皮细胞锌铁调控蛋白（ZRT，IRT—like protein，ZIP）家族低表达密切相关。本文就锌及ZIP家族与前列腺癌关系研究进展作一概述。     

锌及ZIP家族与前列腺癌关系的研究进展

锌是人体中一种重要的微量元素,人体前列腺上皮细胞具有聚集高浓度锌离子的功能,锌在维持正常前列腺功能和前列腺恶性肿瘤发生发展过程中均起着十分重要的作用。前列腺癌组织中锌含量显著低于正常前列腺,但其锌减低机制目前尚不清楚,可能与前列腺上皮细胞锌铁调控蛋白(ZRT,IRT-like protein,ZIP)家族低表达密切相关。本文就锌及ZIP家族与前列腺癌关系研究进展作一概述。     

锌和微量营养素对儿童智能和生长发育的影响

方法：试验分为三组：单纯补锌组（Ｚ），同时补锌＋微量营养素组（Ｚ＋Ｍ），补微量营养素组（Ｍ）。结果：试验前发锌平均含量为２．２８±０．７４μｍｏｌ／ｇ，低于正常值下限共２４人，占受试总人数的２２．２２％。发锌含量与智商呈显著正相关（ｒ＝０．２２９，Ｐ＜０．０５，ｎ＝１０８）。补充试验后三个组发锌变化无显著性差别。Ｚ＋Ｍ组和Ｍ组智商，认知功能的改善好于Ｚ组，Ｚ＋Ｍ组和Ｍ组的差别无统计学意义。膝高的增长值Ｚ＋Ｍ组高于Ｍ组和Ｚ组，Ｍ组高于Ｚ组。结论：受试儿童中锌缺乏并不占主要地位，其他微量营养素的缺乏更应受到重视。同时补充锌和微量营养素可以改善儿童的智能发育，并能促进体格发育。     

Zinc status influences zinc transport by porcine brain capillary endothelial cells

Brain capillary endothelial cells (BCEC) were cultured as an in vitro model of the blood-brain barrier (BBB) and manipulated to investigate how the BBB responds to changes in zinc status. BCEC were grown in minimum essential medium (MEM) with 2% fetal bovine serum and 13% platelet-poor horse serum. A moderate zinc deficiency was imposed by growing the cells in medium containing serums that had previously been dialyzed against EDTA to remove endogenous labile zinc. The control treatment was MEM with undialyzed serums (3 micro mol Zn/L); low-Zn was MEM with dialyzed serums (1.5 micro mol Zn/L); Zn-back was MEM with dialyzed serums, plus ZnCl(2) added back (3 micro mol Zn/L); high-Zn was MEM with undialyzed serums, plus ZnCl(2) (50 micro mol Zn/L). Low-Zn treatment increased (P < 0.02) the rate of zinc uptake into BCEC, relative to control and Zn-back; low-Zn treatment also increased (P < 0.05) the rate of zinc transport across the BCEC into the abluminal chamber (analogous to the brain), relative to control and Zn-back. High-Zn decreased (P < 0.02) the rate of zinc transport across BCEC into the brain, while increasing (P < 0.001) the rate of zinc uptake into BCEC, relative to controls. We conclude that BCEC responded to changes in zinc status by altering the rate of zinc transport in a manner consistent with the BBB actively working to sustain brain zinc homeostasis.     

Gastrointestinal factors influencing zinc absorption and homeostasis

Diet-derived luminal factors have a major influence on zinc available for uptake across the apical membrane of enterocytes. Malabsorption and possibly intestinal microbiota limit this zinc availability. The transporter ZIP4 is expressed along the entire gastrointestinal tract and acts as a major processor of dietary zinc for loading into enterocytes from the apical membrane. Zip4 and other Zip family genes expressed in the gastrointestinal tract are up-regulated in periods of dietary zinc restriction. This provides for powerful homeostatic control. The transporter ZIP14 is up-regulated along the entire gastrointestinal tract by proinflammatory conditions. Intracellular transporters such as ZnT7, influence the transcellular movement of zinc across the enterocyte. Metallothionein, an intracellular metal buffer, and the transporter ZnT1 at the basolateral membrane, regulate the amount of zinc released to the portal circulation for systemic distribution. Pancreatic release of zinc by acinar cells is through the secretory process and apical membrane and involves transporters ZnT2 and ZnT1, respectively. Expression of both transporters is zinc-responsive. Enterocytes and acinar cells constitutively express Zip5 at the basolateral membrane, where it may serve as a monitor of zinc status.     

锌转运体对男性（雄性）生殖作用的研究进展

锌对精子的发育成熟非常关键,而介导锌转运的锌转运体主要来自于锌转运蛋白（Zinc transporter,ZnT）和锌铁调控转运蛋白（Zrt-,Irt-like protein,ZIP）两大家族。在睾丸中,不同的锌转运体依次表达于生精细胞质膜上,参与精子发生和精子形成过程;此外,血睾屏障的维持以及睾酮的生物合成亦需要相应的锌转运体参与。附睾上皮组织高表达ZnT,附睾内精子表面有ZIP1、ZIP5、ZIP6和ZIP8,其有助于精子对锌的吸收且参与精子成熟过程。前列腺腺上皮细胞通过ZIP1吸收血液中的锌,以维持前列腺组织高锌水平;另一方面,该上皮也可通过ZIP2、ZIP3及ZIP4重吸收前列腺液中的锌,确保精浆中重要的抗氧化剂柠檬酸盐的正常分泌。综述锌及其转运体在男性（雄性）生殖中的作用对于了解其生殖过程的发生及男性不育的病理机制均有十分重要的意义。     

Plasma zinc concentration increases within 2 weeks in healthy Senegalese men given liquid supplemental zinc, but not zinc-fortified wheat bread

The responsiveness of plasma zinc concentration to zinc fortification is uncertain. Our objective in this study was to determine whether plasma zinc concentration changes in response to consuming zinc-fortified foods or liquid zinc supplements. We conducted a 4-wk double-blind, randomized trial among 132 healthy Senegalese men ≥ 18 y. Participants received 1 of 4 interventions: 1) (control) 200 g/d of wheat bread fortified with iron and folic acid, but not zinc, and a liquid multivitamin supplement without zinc between meals; 2) (zinc supplement) the same bread and the same multivitamin supplement with 15 mg zinc as ZnSO(4) added; 3) (moderate zinc fortification) the same bread cofortified with 7.5 mg zinc as ZnO and the same multivitamin supplement without zinc; or 4) (high zinc fortification) the same bread cofortified with 15 mg zinc as ZnO and the same multivitamin supplement without zinc. Fasting blood samples were collected twice at baseline and at d 15 and 29 of the intervention. There was no significant interaction between group and study day (P = 0.11). However, at d 15, the mean change in plasma zinc concentration in the zinc-supplemented group was greater than in the placebo and fortification groups ( 0.72 μmol/L vs. -0.09 to 0.03 μmol/L; P = 0.05). At d 29 there were no significant group-wise differences. Across all time points, the zinc-supplemented group was the only group where plasma zinc concentration increased from baseline (P = 0.006). These results suggest that plasma zinc concentration may not be a sufficiently sensitive indicator to evaluate short-term responses to zinc fortification.     

Nutritionally regulated biomarkers for breast cancer

Recent data on the expression and function of the ZIP family of proteins has suggested that these zinc transporters may be useful biomarkers for the diagnosis and prognosis of human breast cancer. This exciting new area of research opens the door for the use of a variety of nutritionally regulated genes and proteins as screening tools not only for breast cancer, but for a variety of other diseases for which early detection is important.     

Impact of zinc metabolism on innate immune function in the setting of sepsis

Individuals at highest risk of zinc deficiency (children, elderly, pregnant and lactating women, morbidly ill, alcoholics) have a higher risk of infection. Whereas the essential role of zinc in maintaining adaptive immunity is well recognized, much less is known regarding the innate immune system. We recently reported that zinc deficiency significantly increases mortality in an animal model of sepsis. In particular, zinc-deficient mice had a decreased capacity to clear bacteria and a concomitant increase in NF-kappaB-mediated signaling across multiple vital organs. This occurred in tandem with exaggeration of the acute phase and innate immune response. Strikingly, sepsis patients revealed similar findings in that lower plasma zinc levels were associated with more inflammation and increased severity of illness. Through these investigations we have consistently observed that SLC39 A8 (ZIP8) is unique, relative to other zinc transporters, in that its expression is significantly induced at the onset of infection. Moreover, induction of ZIP8-mediated zinc transport into innate immune cells is vital for proper immune function. Whether ZIP8 functions beyond the conventional role of a zinc transporter remains a work in progress, although new evidence has revealed that ZIP8 expression itself is regulated by NF-kappaB. Taken together, these findings indicate that zinc is vital for proper innate immune function and that hZIP8 is intricately involved in maintaining innate immune defense.     

醋酸铅染毒人外周血淋巴细胞诱发XRCC1、hOGG1基因表达变化的研究

目的 研究醋酸铅染毒人外周血淋巴细胞对XRCC1、hOGG1基因表达变化的影响。方法 用0、20、40和80μmol/L浓度醋酸铅染毒人外周血淋巴细胞24h, 采用qPCR法和Western-Blot法测定XRCC1、hOGG1基因的mRNA和蛋白表达水平。结果 与对照组相比,醋酸铅染毒诱导人外周血淋巴细胞XRCC1、hOGG1基因的mRNA和蛋白表达水平随醋酸铅染毒浓度增加而下降,差异有统计学意义(P<0.01)。结论 醋酸铅染毒抑制XRCC1、hOGG1基因表达水平,导致细胞对DNA损伤修复能力下降。     

Lineage-specific and differentiation-stage-specific gene expression in normal and leukaemic human myeloid cells.

One example of each of two approaches to the isolation of molecular hybridization probes and their use for the comparative investigation of gene expression and its control during differentiation of normal and leukaemic leukocytes is described. RNA preparations from the peripheral blood leukocytes of human leukaemias of various types were assayed for the relative abundance of the mRNA homologous with a cellular oncogene, c-myc. All types of leukaemia except chronic lymphatic leukaemia (CLL) showed varying levels of myc-related RNA; the highest concentrations occurred in cell populations in which blast cells predominated. In contrast, a recombinant plasmid (pCG14), isolated from a cDNA recombinant plasmid library that represented polyadenylated RNAs from the peripheral blood leukocytes of a chronic granulocytic leukaemia (CGL), hybridized with an mRNA whose occurrence is diagnostic of CGL leukocytes. This mRNA was also found in normal bone marrow cells; in both bone marrow and in CGL leukocytes, pCG14-homologous RNA occurs only in cells around the myelocyte stage in differentiation. It is suggested that these probes, and others for mRNAs whose occurrence is specific to a particular cell lineage and/or stage in differentiation, detect a new series of potential diagnostic markers. These might usefully supplement existing ones to provide a more detailed, objective subclassification of the leukaemias which could have important implications for diagnosis and therapy.     

南充地区0～5岁儿童末梢全血锌元素分析

目的 检测四川省南充地区0～5岁儿童末梢全血锌含量,评估该地区0～5岁儿童锌缺乏情况,为合理锌补给提供指导.方法 采用火焰原子吸收法对南充地区419名0～5岁儿童末梢全血微量元素锌分析.结果 各年龄段各性别组末梢全血锌含量为:0～岁男童为65.90±16.81μmol/L、女童为67.43±22.75μmol/L;1～岁男童为74.25±18.84μmol/L、女童为72.22±18.08μmol/L;2～5男童为85.94±18.83μmol/L、女童为82.27±18.34μmol/L.各年龄组之间两两比较具有显著差异(P<0.05),但同年龄段不同性别之间无显著性差异(P>0.05);锌缺乏方面,以0～岁组最为显著(55.81%),1～岁组次之(41.61%),2～5岁组最低(11.96%),经比较有统计学意义(χ2分别为4.42、38.38、58.70,均P<0.05),各年龄组不同性别之间比较无显著性差异(P>0.05).结论 南充地区0～5岁儿童各年龄段末梢全血锌元素含量和锌缺乏率差异显著,应合理补充微量元素锌.