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。     

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。     

锌转运体研究进展

锌转运体 ( Zn T)的发现深化了对锌在细胞和分子水平的认识。迄今为止所克隆出的 4种哺乳动物Zn T( Zn T1、Zn T2、Zn T3、Zn T4 )在蛋白结构上具有 6个跨膜域、富组氨酸胞内袢、C,N末端位于胞内等共性。对 Zn T的分布及基本功能进行了初步研究。Zn T1分布广泛 ,位于细胞膜上 ,可使细胞内锌外排 ;Zn T2分布于肠、肾、睾丸 ,Zn T3主要分布于脑、睾丸 ,Zn T4分布于乳腺、脑、睾丸 ,Zn T2、Zn T3、Zn T4均定位于胞内囊泡膜上 ,且功能相似 ,可使细胞内锌转运入囊泡。通过 Zn T对胞内锌的这种外排或胞内转运作用 ,可使细胞避免高锌引发的细胞毒性。涉及锌的非专一性转运体包括二价金属离子转运体 ( DMT1)、调控锌铁的转运体样基因 ( ZIRTL)和人类调控锌铁蛋白 ( h ZIP2 )等。另外 ,对非哺乳动物涉及锌转运的组分作了简要介绍     

锌转运体的结构预测、转运机制和功能

机体维持细胞内锌内稳态具有很重要的意义,因而研究锌转运体的结构、转运机制和功能非常有必要。锌转运体家族种类很多,大体可以分为以下3种:Zrt-Irt样蛋白家族、助阳离子扩散体家族和双价金属转运体家族。Zrt-Irt样蛋白家族的主要功能是摄取锌进入细胞内,以补充细胞内锌的不足;而助阳离子扩散体家族成员主要参与锌的外排和锌在细胞内的区室化,以达到降低细胞内锌浓度并贮存锌到细胞器中的目的。双价金属转运体家族具有潜在锌转运活性,但目前尚有争议。     

009 锌转运体研究进展

锌转运体(ZnT)的发现深化了对锌在细胞和分子水平的认识.迄今为止所克隆出的4种哺乳动物ZnT(ZnT1、ZnT2、ZnT3、ZnT4)在蛋白结构上具有6个跨膜域、富组氨酸胞内袢、C,N末端位于胞内等共性.对ZnT的分布及基本功能进行了初步研究.ZnT1分布广泛,位于细胞膜上,可使细胞内锌外排;ZnT2分布于肠、肾、睾丸,ZnT3主要分布于脑、睾丸,ZnT4分布于乳腺、脑、睾丸,ZnT2、ZnT3、ZnT4均定位于胞内囊泡膜上,且功能相似,可使细胞内锌转运入囊泡.通过ZnT对胞内锌的这种外排或胞内转运作用,可使细胞避免高锌引发的细胞毒性.涉及锌的非专一性转运体包括二价金属离子转运体(DMT1)、调控锌铁的转运体样基因(ZIRTL)和人类调控锌铁蛋白(hZIP2)等.另外,对非哺乳动物涉及锌转运的组分作了简要介绍.     

锌转运体研究发展

锌转运（ZnT)的发现深化了对锌在细胞和分子水平的认识。迄今为止所克隆出的4种哺乳动物ZnT(ZnT1、ZnT2、ZnT3、ZnT4）在蛋白结构上具有6个跨膜域、富组氨酸胞内袢、C，N末端位于内等共性。对ZnT的分布及基本功能进行了初步研究。ZnT1分布广泛，位于细胞膜上，可使细胞内锌外排；ZnT2分布于肠、肾、睾丸，ZnT3主要分布于脑、睾丸，ZnT4分布于乳腺、脑、睾丸，ZnT2、ZnT3、ZnT4、均定于胞内囊泡膜上，且功能相似，可使细胞内锌转运入囊泡。通过ZnT对胞内锌的这种外排或胞内转运作用，可使细胞避免高锌引发的细胞毒性。涉及锌的非专一性转运体包括二价金属离子转运体（DMT1）、调控锌铁的转运体样基因（ZIRTL）和人类调控锌铁蛋白（hZIP2）等。另外，对非哺乳动物涉及锌转运的组分作了简要介绍。     

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。     

低锌浓度培养基对Caco2细胞二价金属离子转运体mRNA表达的影响

锌是人体必需的微量营养素之一，锌缺乏或过量与多种机能紊乱相关。二价金属离子转运体（divalent metaltransporter 1，DMT1）是近期发现的哺乳动物金属离子转运体，在机体所有组织几乎均有表达，具有对铁、锌等多种二价金属离子的转运功能。我们既往的实验结果显示膳食高锌可以导致断乳小鼠睾丸DMT1 mRNA表达显著降低，约为适锌时表达量的1／3～1／4，提示可能为哺乳期后幼鼠维持锌内稳态的一种反馈保护机制，但是脑组织中的DMT1 mRNA表达未见变化，提示在脑组织锌转运中DMT1可能不作为主要的转运体。小肠是锌吸收的重要场所，DMT1是否参与小肠锌吸收过程？我们以不同锌浓度培养的Caco2细胞为模型，观察其对DMT1 mRNA表达的影响及其规律，探讨DMT1在小肠锌吸收中的可能作用。     

维生素D补充对糖尿病模型大鼠胰岛铁过载和β细胞凋亡的影响

目的探讨维生素D(VD)补充对糖尿病模型(ZDF)大鼠胰岛铁过载和β细胞凋亡的影响。方法雄性5～6w Zucker瘦型(ZL)大鼠为对照组(ZL+VD.Def),ZDF大鼠按照体质量随机分为模型VD缺乏(ZDF+VD.Def)及模型VD补充(ZDF+VD,8μg/kg·bw)2组,喂养7w。应用HE染色、胰岛素免疫组化、TUNEL荧光观察胰岛损伤、β细胞数量及凋亡情况,用增强普鲁士蓝、蛋白质免疫印迹观察胰腺铁沉积及caspase3和铁代谢相关蛋白水平。结果与ZL+VD.Def组相比,ZDF+VD.Def组胰岛损伤严重,β细胞数量减少,凋亡增加,胰腺c-caspase3蛋白水平增加(P0.01);与ZDF+VD.Def组相比,ZDF+VD组胰岛损伤减轻,β细胞数量增加,凋亡减少,胰腺c-caspase3蛋白水平降低(P0.01);与ZL+VD.Def组比较,ZDF+VD.Def组胰岛存在明显铁沉积,胰腺铁蛋白轻链(ferritin light chain,FTL)、铁蛋白重链(ferritin heavy chain,FTH)、二价金属离子转运体1(divalent metal ion transporter 1,DMT1)、锌铁调控转运蛋白14(zrt/IRT-like protein 14,ZIP14)蛋白水平分别增加至23(P0.001)、3.7(P0.01)、2.1(P0.01)、4.2(P0.001)倍,转铁蛋白受体1(transferrin receptor 1,TfR1)蛋白水平降低38%(P0.05),转铁蛋白受体2(transferrin receptor 2,TfR2)蛋白水平无明显改变;与ZDF+VD.Def组比较,ZDF+VD组胰岛铁沉积明显减轻,胰腺FTL、FTH、DMT1、ZIP14蛋白水平分别降低76%(P0.01)、54%(P0.05)、62%(P0.001)、71%(P0.001),TfR1和TfR2蛋白水平无明显改变。结论 VD可能通过调节铁代谢相关蛋白,缓解ZDF大鼠胰岛铁过载,减少β细胞凋亡。[营养学报,2019,41(6):587-592]     

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.     

A new mutation in exon 3 of the SCL39A4 gene in a Tunisian family with severe acrodermatitis enteropathica

Acrodermatitis enteropathica is a rare autosomal recessive disease that manifests as an inability of the affected individual to absorb intestinal zinc, and therefore patients have nutritional zinc deficiency. Without zinc therapy, this condition is fatal. Mutations in the SLC39A4 gene are responsible for acrodermatitis enteropathica. This gene encodes one member of a human zinc/iron-regulated transporter-like protein, also known as ZIP4, and consists of 12 exons and spans about 4.7 kb. We describe a novel mutation in a Tunisian family in which a chain termination codon in exon 3 yielded a truncated ZIP4 zinc transporter protein.     

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。     

Investigation of lymphocyte gene expression for use as biomarkers for zinc status in humans

A bioassay for zinc status in humans has been sought due to the importance of zinc, an essential trace metal, for many divergent functions in the human body; however, a sensitive bioassay for zinc status in humans is lacking. To address this issue, we established gene expression profiles of human lymphoblastoid cells treated with 0 or 30 micro mol/L ZnSO(4) using microarray technology. A limited number of genes were responsive to 30 micro mol/L zinc based on the analysis of Affymetrix human genome U133A GeneChips. We also examined the gene expression patterns of zinc transporters in human lymphoblastoid cells using quantitative RT-PCR analysis. ZNT1 was upregulated in lymphoblastoid cells, whereas ZIP1 was downregulated in response to the increased zinc concentrations in the culture media. To evaluate the potential applications of using both zinc transporter genes as biomarkers of zinc status, we measured the expression levels of ZIP1 and ZNT1 in the peripheral leukocytes collected from 2 different age groups of Korean women. After administration of a zinc supplement (22 mg zinc gluconate/d for 27 d), ZIP1 expression decreased by 17% (P < 0.01) and 21% (P < 0.05) in the peripheral leukocytes collected from 15 young (20-25 y) and 10 elderly (64-75 y) subjects, respectively. ZNT1 expression was not affected by taking the zinc supplement. These data suggest a potential application of ZIP1 as a biomarker of zinc status in humans.     

Geographic Access to Family Planning Facilities and the Risk of Unintended and Teenage Pregnancy

Objectives: This study tested the hypotheses that greater geographic access to family planning facilities is associated with lower rates of unintended and teenage pregnancies. Methods: State Pregnancy Risk Assessment Monitoring System (PRAMS) and natality files in four states were used to locate unintended and teenage births, respectively. Geographic availability was measured by cohort travel time to the nearest family planning facility, the presence of a family planning facility in a ZIP area, and the supply of primary care physicians and obstetric-gynecologists. Results: 83% of the PRAMS cohort and 80% of teenagers lived within 15 min or less of a facility and virtually none lived more than 30 min. Adjusted odds ratios did not demonstrate a statistically significant trend to a higher risk of unintended pregnancies with longer travel time. Similarly there was no association with unintended pregnancy and the presence of a family planning facility within the ZIP area of maternal residence, or with the supply of physicians capable of providing family planning services. Both crude and adjusted relative rates of teenage pregnancies were significantly lower with further distance from family planning sites and with the absence of a facility in the ZIP area of residence. In adjusted models, the supply of obstetricians-gynecologists and primary care physicians was not significantly associated with decreased teen pregnancies. Conclusions: This study found no relationship between greater geographic availability of family planning facilities and a risk of unintended pregnancies. Greater geographic availability of family planning services was associated with a higher risk of teenage pregnancy, although these results may be confounded by facilities locating in areas with greater family planning needs.     

The association of poverty and low immunization rates in ZIP code areas. A retrospective survey of Minnesota kindergartners

This study evaluated indicators of poverty in Minnesota ZIP code areas with low childhood immunization rates. During 1996-1997, a retrospective survey of 68,639 Minnesota kindergarten children was conducted; 68% received four doses of diphtheria, tetanus, and pertussis vaccine, three doses of polio vaccine, and one dose of measles, mumps, and rubella vaccine (4:3:1) by 24 months of age. Of 447 ZIP codes further evaluated, 24 (5%; 13 urban and 11 rural) had 4:3:1 immunization rates at 24 months of < or = 50%. None of 159 ZIP codes in which < 5% of residents were below the poverty line had immunization rates < or = 50%, compared with 9 (32%) of 28 ZIP codes with > or = 15% of residents below the poverty line (p < 0.001). Immunization rates were lowest in ZIP codes with a lower median family income and greater proportion of residents below the poverty line. Surveys such as this can help immunization programs target and monitor prevention activities for these pockets of need.