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     

锌与前列腺肿瘤的关系

锌与前列腺肿瘤的关系张建业张莲英庞维秋（山东医科大学济南２５００１２）前列腺是人体锌含量最高的组织之一，前列腺良性增生和癌变时前列腺组织的Ｚｎ２＋含量发生明显改变。前列腺良性增生（ＢＰＨ）和前列腺癌（ＰＣ）是常见的老年男性疾病，可能与某些环境因子有关...     

保护男子性功能的食品

锌是人体所必需的微量元素之一,缺锌可以引起男子输精管萎缩,睾丸、附睾、前列腺发育迟缓,睾丸上皮细胞萎缩,以至性功能低下、阳痿、男性不育等症.     

锌缺乏与多补都有害

锌是人体所必需的微量元素之一，正常成人体内含锌约2克。 锌分布于人体各组织器官内，视网膜、脉络膜、前列腺等器官含量最多，胰腺、肝、肾、肌肉等组织也含有较多的锌。锌与许多酶的活性有关；参与维生素A和视黄醇结合蛋白的合成；在核酸合成中起重要作用，参与机体免疫功能；影响维生素C的排泄量，与脂肪酸和维生素E有协同作用。     

前列腺癌患者血清sE—cad检测的临床意义

目的 探讨与张力蛋白在10号染色体同源缺失的上皮细胞钙黏素（E-Cad）在前列腺癌组织中的表达技其临床意义。方法应用免疫组织化学（SP）方法检测42例前列腺癌、13例正常前列腺组织和17例良性前列腺增生组织中E-cad垂白的袁达。结果前列腺癌组织中E-Cad蛋白表达的阳性率为50．0％（21／42）；随肿瘤细胞病理分级、临床分期程度的增高，癌细胞表达E—Cad蛋白阳性率降低，各组间比较差异有显著性（P〈0．01或P〈0．05）；正常前列腺组织和良性前列腺增生组E-Cad蛋白均呈阳性免癌反应。结论E—Cad蛋白异常表达在前列腺癌的恶性进展中起重要作用，检测E—Cad蛋白表达有利于判断病期殁预后。     

缺锌少硒影响男性健康

锌,是维系人体健康,促进发育生长,加强免疫系统和调节脑细胞功能的重要微量元素之一,正常人体中的锌总量大约有33.3克左右,主要分布在人体皮肤、肌肉、肝脏、头发、唾液、睾丸、附睾、前列腺、骨骼、红细胞和眼球等器官中,尤以睾丸、肌肉、骨骼、皮肤的储量最高.     

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.     

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.     

Dietary zinc deficiency decreases glutathione S-transferase expression in the rat olfactory epithelium

Zinc deficiency leads to olfactory and gustatory dysfunction, but little is known about the underlying molecular mechanism of this phenomenon. We examined the effect of dietary zinc deficiency on the rat olfactory epithelium. Immunoreactivities of glutathione S-transferase (GST) mu, neuron-specific enolase (NSE) and proliferating cell nuclear antigen (PCNA), and in situ hybridization of GST mu mRNA in the olfactory epithelia were examined under different dietary zinc intake conditions. Adult male rats were fed a zinc-deficient (ZD) diet (0.5 mg zinc/kg diet), whereas control rats, including pair-fed (PF) and zinc-adequate (ad libitum consumption, AL) groups, were fed a zinc-adequate diet (58 mg zinc/kg diet) for 7 wk. We also examined the effect of zinc replacement (ZR) by subsequently feeding half of the ZD group a zinc-adequate diet for 5 wk after the initial 7-wk deprivation. No significant differences in immunoreactivity for NSE in olfactory epithelial receptor cells or for PCNA in basal cells were noted among groups. Intense GST mu immunoreactivity and hybridization signals were observed in olfactory supporting cells of AL, PF and ZR groups, but very minimal or no such signal was noted in ZD rats. Our findings indicated that zinc deficiency reduces GST mu expression in the supporting cells of rat olfactory epithelia but does not affect receptor cell proliferation or maintenance.     

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.     

表皮生长因子受体及PI3K在硫酸锌诱导人呼吸道上皮细胞间粘附分子-1表达过程中的作用

目的探讨硫酸锌对上皮细胞内细胞间粘附分子-1(ICAM-1)表达的影响及其分子生物学机制。方法应用PCR与蛋白质免疫印迹试验检测硫酸锌诱导人呼吸道上皮细胞ICAM-1mRNA与蛋白的表达,以及表皮生长因子受体(EGFR)及PI3K的活化。结果硫酸锌可诱导ICAM-1mRNA与蛋白的过量表达。在同一试验条件下,硫酸锌可诱发EGFR及磷脂酰肌醇3激酶(PI3K)下游激酶Akt的磷酸化或活化。用EGFR抑制剂(PD153035)及PI3K抑制剂(LY294002)预处理上皮细胞,可明显抑制硫酸锌对ICAM-1表达的诱导作用。结论硫酸锌可激活EGFR与PI3K/Akt信号传导通路,进而上调ICAM-1的表达。     

Zinc and the Eye

Zinc, a trace element that influences cell metabolism through a variety of mechanisms, appears to play an integral role in maintaining normal ocular function. This element is present in high concentrations in ocular tissue, particularly in retina and choroid. Zinc deficiency has been shown in a number of species to result in a variety of gross, ultrastructural and electrophysiologic ocular manifestations. The physiological functions for zinc have been studied predominantly in retina and retinal pigment epithelium where zinc is believed to interact with taurine and vitamin A, modify photoreceptor plasma membranes, regulate the light-rhodopsin reaction, modulate synaptic transmission and serve as an antioxidant. Suboptimal zinc status in North America may influence the development and progression of several chronic eye diseases. Zinc supplementation trials and epidemiological studies have produced conflicting results concerning the role of zinc in age-related macular degeneration. Additional well-controlled supplementation trials are indicated to clarify the role of zinc in this disease. Future investigations must also expand our understanding of the mechanisms by which zinc regulates ocular morphology and function.