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。     

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.     

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。     

锌铁调控蛋白ZIP的结构和功能

锌铁调控蛋白ZIP隶属金属离子转运体超家族 ,其基因家族成员首先在植物中被发现 ,随后在多种动植物水平被克隆。ZIP转运体可转运众多阳离子 ,包括Ca2 + ,Fe2 + ,Mn2 + 及Zn2 + 等。了解ZIP转运体在动植物中如何发挥离子转运功能 ,对从分子水平认识金属离子缺乏或蓄积的机理有着重要的理论意义和广泛的应用价值。本文就最近在拟南芥Arabidopsis中发现的一个新的金属离子转运体家族 -锌铁调控蛋白ZIP家族的结构及其成员的功能进行综述     

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。     

附睾分泌蛋白研究进展

精子在附睾内移行的过程中与附睾分泌的蛋白质相互作用，获得了运动能力和受精能力，达到了功能上的成熟。研究与精子成熟相关的附睾分泌蛋白，有助于加深对男性生殖及其调控的理解，同时有可能发现新的男性避孕靶点。附睾分泌的具有转运或结合功能的蛋白质（如HE1）、或者具有酶活性的蛋白（如糖苷酶、糖基转移酶和蛋白酶）参与了精子质膜重塑；蛋白DE，P26h／F34H，ARP等能与精子结合，可能与精卵融合相关；Bin1b与精子运动能力的获得相关；乳铁蛋白，HE2，EP2，2D6，ESC42，ESP13．2，E3，hCAP18和Eppin等具有抗微生物作用，对精子起保护作用。     

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。     

饲粮锌水平对肉仔鸡组织锌转运蛋白基因表达的影响

目的研究饲粮中不同水平锌对肉仔鸡组织锌转运蛋白基因表达的影响。方法选用1d龄AA肉公鸡720只,随机分为8个处理组,每个处理6个重复,分别饲喂不加锌的玉米-豆粕型基础饲粮(对照组)和添加水平为20、40、60、80、100、120和140mg/kg硫酸锌的饲粮,试验期21d,分为1～7d龄,8～14d龄和15～21d龄三阶段进行。结果各日龄胰脏锌转运蛋白-2的基因表达均受到饲粮锌水平显著的影响,7d龄时随饲粮锌添加量的增加呈明显的渐近线变化趋势,而14d龄与21d龄均呈二次曲线变化趋势。本研究表明,胰脏ZnT2mRNA水平可以敏感的反应肉仔鸡锌的营养状况,提供了一个新的锌营养标识;在肉仔鸡体内锌的稳恒调节作用中,ZnT2可能为第一道防线,当饲粮锌含量超过一定范围时,其它锌稳恒调节蛋白如MT等则发挥着重要的作用。结论胰脏ZnT2mRNA水平可以敏感地反应肉仔鸡锌的营养水平,在肉仔鸡体内锌起稳恒调节作用。     

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.     

Pharmacokinetics of Zinc Tannate After Intratesticular Injection

Forty-eight sexually mature male rats were injected intratesticularly with either 1, 3, or 6 mg zinc tannate (Kastrin) or with saline (as control). Zinc localized only in low concentration in primary spermatocytes and could not be detected in spermatogonia, Sertoli cells, spermatids, or spermatozoa. Forty-eight hours after injection of 1 mg Kastrin, zinc was accumulated in the spermatogonia and primary spermatocytes while, after injection of 3 mg, zinc was preferentially localized in Sertoli cells and spermatids; however, zinc was observed in the spermatids and spermatozoa 48 h after injection iwth 6 mg, and germ cells lost their identity and were fragmented after 1 week.     

Zinc transporters 1, 2 and 4 are differentially expressed and localized in rats during pregnancy and lactation

Zinc metabolism is controlled within relatively restricted limits throughout the life cycle. Expression and localization of zinc transporters 1, 2 and 4 during pregnancy and lactation in small intestine, mammary gland and liver of the rat were investigated using Northern analysis, Western blotting and immunohistochemistry. In maternal tissues, zinc transporter 4 was the most widely expressed among these zinc transporters in the tissues examined. In small intestine and liver, zinc transporter 4 increased from levels found during late gestation, but zinc transporter 1 did not. Zinc transporter 2 expression in small intestine was transient, being highest around parturition, and was not detected in liver. Immunohistochemistry revealed unique patterns of zinc transporter localization at different stages of development. In the placenta, zinc transporters 1 and 4 were found concentrated along the villous visceral splanchnopleure. In the mammary gland, zinc transporter 4 was most abundant in cells surrounding the alveolar ducts and oriented to the basement lamina. All three transporters were highly expressed in neonatal small intestine, principally near the apical surface, but zinc transporters 1 and 4 increased in abundance at the basolateral surface during development. Zinc transporter 2 was oriented apically, directly adjacent to the microvilli of enterocytes. Within the intestine, expression of each transporter was limited to enterocytes. These results support a role for these transporters in maintaining an adequate zinc supply derived from the maternal diet for zinc acquisition and use by the fetus and neonate.     

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.     

Cellular transporters for zinc

Nutritionally essential metals such as zinc are moved into and out of cells by a series of transport proteins or transporters. Their tri-fold purpose is to procure zinc from the environment, to protect cells against zinc toxicity, and maintain ample supplies of zinc for metabolic purposes. Two families of zinc transporters are known: the ZIP family that imports zinc and the ZnT family that functions in releasing zinc or sequestering zinc internally.     

Zinc and Cancer: Implications for LIV-1 in Breast Cancer

Zinc is a trace mineral which is vital for the functioning of numerous cellular processes, is critical for growth, and may play an important role in cancer etiology and outcome. The intracellular levels of this mineral are regulated through the coordinated expression of zinc transporters, which modulate both zinc influx as well as efflux. LIV-1 (ZIP6) was first described in 1988 as an estrogen regulated gene with later work suggesting a role for this transporter in cancer growth and metastasis. Despite evidence of its potential utility as a target gene for cancer prognosis and treatment, LIV-1 has received relatively little attention, with only three prior reviews being published on this topic. Herein, the physiological effects of zinc are reviewed in light of this mineral's role in cancer growth with specific attention being given to LIV-1 and the potential importance of this transporter to breast cancer etiology.     

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。