肾上腺皮质激素对水通道蛋白表达的调节

肾上腺皮质激素参与水盐代谢的调节,盐皮质激素和糖皮质激素调节上皮细胞水通道蛋白 (Aquaporins,AQPs)的表达。盐皮质激素可使肾脏AQP3表达上调,对肾脏的AQP2表达依据刺激的时间不 同而表达不同,但对AQP1没有影响。糖皮质激素对不同组织器官AQPs的影响不尽相同。肾上腺皮质激素 对AQPs的调节作用在某些水代谢紊乱疾病的诊断与治疗方面可能有着广阔的应用前景。     

水通道在冷冻保存中的应用研究进展

水通道(aquaporins,AQPs)是一类参与水快速转运的跨膜蛋白家族,广泛分布于动物、植物及微生物的生物膜表面,精细参与调节细胞跨膜的渗透平衡。近年来,AQPs在细胞转运水和冷冻保护剂中的作用倍受关注,AQPs能提高某些细胞和组织的冻融存活率,在低温保存中具有一定的应用前景。     

肾脏水通道蛋白的研究进展

细胞内外水平衡是维持生命的关键因素之一。在发现水通道蛋白(Aquaporins，AQPs)以前，生理学家一直认为水是通过膜脂质双层结构进行简单扩散，但在某些组织细胞如红细胞、肾近曲小管细胞对水通透性甚高，不能用简单扩散来解释，于是推测此类细胞膜上可能存在某种功能性转运水的通道。1988年     

山莨菪碱增加急性肺损伤大鼠肺组织AQP1和AQP5表达

有研究表明,山莨菪碱(又称654-2)可抑制肺内炎症反应,减轻非心源性肺水肿,能有效的治疗急性肺损伤[1],但其作用机制还不十分明确.水通道蛋白(aquaporins,AQPs)是一组介导水跨生物膜转运的细胞膜转运蛋白,对维持肺实质中的水平衡具有重要作用.     

水通道蛋白与肿瘤

水通道蛋白（AQPs）是一类小分子质量的、膜内嵌蛋白,它所介导的自由水快速被动的跨生物膜转运,是水进出细胞的主要途径。AQPs大量表达于不同组织来源的肿瘤细胞,特别是侵袭性肿瘤。AQPs高表达的肿瘤细胞在体外表现为较强的迁移能力,体内则表现为局部侵袭力增强,渗出增多以及转移灶增多。抑制AQPs的表达将有可能为肿瘤的治疗提供帮助。     

水通道蛋白调节剂对脑部疾病潜在的治疗价值

水通道蛋白(Aquaporins,AQPs)是一种膜蛋白,主要介导水分高效特异的跨膜转运.中枢神经系统主要表达AQP1、AQP4,参与控制脑组织水分的平衡,细胞的迁移和神经元的兴奋性.AQP4调节剂可作为脑卒中、外伤、肿瘤、感染、脑积水和癫痫新的治疗策略.在此我们就水通道蛋白在中枢神经系统的表达、作用及疾病研究中的新进展作一综述.     

水通道蛋白在鼠肺发育过程中的变化及意义

目的： 探讨水通道蛋白（AQPs）mRNA及蛋白表达在鼠肺发育过程中的变化及意义。方法: 以胎鼠、新生鼠、幼鼠和成年大鼠为研究对象,采用逆转录-聚合酶链反应（RT-PCR）和免疫组织化学（SABC）方法分别检测几种主要水通道AQP1、AQP3、AQP4和AQP5 mRNA及蛋白在肺脏的表达和分布;同时测定肺发育过程中一些相关指标,进行对比分析。结果: 大鼠肺发育连续不断,从胎鼠至新生鼠期增长最快,以后增速减慢,为一个动态的过程。肺AQPs mRNA在胎鼠时均开始微量转录,仅出现AQP1蛋白表达,出生后AQPs mRNA及蛋白均快速增加,呈增量表达至成年期。相关性分析显示,AQPs变化与肺发育指标变化存在显著正相关（P<0.05）。结论: AQPs可能参与了大鼠肺发育的诸多重要生理过程。     

地塞米松对水通道蛋白1、4、5在大鼠变应性鼻炎鼻黏膜中表达的影响及意义

目的:确定水通道蛋白(AQPs)在大鼠变应性鼻炎时鼻黏膜上的表达及分布,并观察地塞米松对AQPs表达的影响,探讨AQPs与变应性鼻炎时水液分泌的关系.方法:健康SD大鼠随机分成空白组、假处理组、模型组、干预组,组织化学方法观察各组组织形态学特征,免疫组织化学方法(SP法)检测各组AQPs的表达并进行比较.结果:AQP1在血管内皮细胞、成纤维细胞中表达较强;AQP4表达于上皮细胞和上皮内腺上皮细胞及部分上皮下的腺上皮细胞;AQP5在上皮下部分腺上皮细胞成簇表达.经地塞米松处理后,AQP1、4、5的表达均有明显变化,仅AQP4在干预组间的表达并无明显改变.结论:AQP1、4、5在大鼠鼻黏膜上有不重叠表达;地塞米松能调节AQPs在鼻黏膜上的表达.     

水通道蛋白4的研究进展

长期以来人们认为水的跨膜转运主要通过简单扩散,然而1991年Peter Agre课题组在红细胞膜上发现了一种对水有特异性通透的蛋白分子[1],被定义为水通道蛋白(aquapor-ins,AQPs).迄今为止,已发现200余种水通道蛋白,在哺乳动物中,已克隆和鉴定出13种水通道蛋白(AQP0-AQP12)[2].     

胎儿发育中水通道蛋白的免疫组化观察

目的观察胎儿器官和组织发育过程中水通道蛋白(AQPs)的表达特征,初步探讨AQPs对胎儿发育进程的生物意义。方法14～38周胎儿共12例,取用肾脏、肺脏、唾液腺、甲状腺和胃等器官,常规固定、石蜡包埋和切片;用免疫组化S-P法,检测AQPs(AQP1、AQP2和AQP4)在胎儿不同胎龄器官组织中的表达。结果胎儿肾脏中AQPs定位于近端小管和集合管系统;胎肺中AQPs的表达随肺泡发育分化而迁移,始终定位于肺泡上皮;晚期胎肺中AQPs于肺泡及呼吸道上皮均有表达;胎16周起检出AQPs反应于唾液腺、胃腺和胰腺等消化腺,同时甲状腺中AQPs在滤泡上皮也有活跃表达。结论胎肾中AQPs的表达与肾的重吸收功能直接相关;胎肺内AQPs的表达反映肺泡上皮分化的轨迹,其调节水分的作用为肺泡发育提供空间;AQPs介导细胞内外水分的转运不但调节消化腺的分泌还参与调节甲状腺滤泡的激素合成和分泌过程。表明AQPs在胎儿发育过程,对各器官中水转运功能的成熟起重要作用。     

水通道蛋白与肿瘤血管新生

肿瘤血管新生对于肿瘤的生长具有重要作用。水通道蛋白在肿瘤组织中常出现表达异常，并且可以促进肿瘤血管的新生及包括肿瘤血管内皮在内的多种细胞的迁移，与此同时，水通道蛋白与肿瘤血管的高通透性有关，这可能是肿瘤组织对水通道蛋白缺失具有较高敏感性的原因。鉴于水通道蛋白对于肿瘤特别是肿瘤血管新生的影响，其抑制剂可能成为新的肿瘤治疗的目标靶点。     

肺脏的水孔蛋白家族

90年代以来 ,作为膜上水分子通道的水孔蛋白(ａｑｕａｐｏｒｉｎｓ ,ＡＱＰｓ)家族克隆成功[1,2 ] ,对自由水被动跨膜转运机制做出更加形象而深入的解释。肺脏的许多生理功能都有水分子运动的参与 ,同时许多肺脏疾病 ,如哮喘、肺水肿和急性呼吸窘迫综合征等也涉及肺内水运动平衡的紊乱。因此肺内水孔蛋白的分布及其病理生理意义日益受到重视。1　水孔蛋白的结构与功能特点水孔蛋白属于膜主体内在蛋白 (ｍａｊｏｒｉｎｔｅｒｎａｌｐｒｏｔｅｉｎ ,ＭＩＰ)家族的成员 ,目前在人类和哺乳动物身上共发现 10个亚型 ,广泛分布于多个组织器官 ,具…     

Function of aquaporins in female and male reproductive systems

The flow of water and some other small molecules across cell membranes is important in many of the processes underlying reproduction. The fluid movement is strongly associated with the presence of aquaporins (AQPs) in the female and male reproductive systems. It has been suggested that AQPs mediate water movement into the antral follicle and play important roles in follicle development. AQPs are known to be involved in the early stage of spermatogenesis, in the secretion of tubule liquid and in the concentration and storage of spermatozoa. Fluid reabsorption in some regions of the male reproductive tract is under steroid hormone control and could be mediated by various AQPs. Also AQPs take part in the processes of fertilization, blastocyst formation (as the pathway for transtrophoectodermal water movement during cavitation) and implantation. Alterations in the expression and function or regulation of AQPs have already been demonstrated in disorders of the male reproductive system, such as abnormal sperm motility, the abnormal epididymis and infertility seen in cystic fibrosis, and varicocele. This article extensively reviews the distribution of AQPs in mammalian reproductive tissues and discusses their possible physiological and pathophysiological roles.     

Intracellular aquaporins: clues for intracellular water transport?

Aquaporins (AQPs) are usually present at the plasma membrane to regulate influx and outflow of water and small molecules. They are important for the regulation of water homeostasis for the cells and organisms. AQPs are also present inside the cell, at the membranes of intracellular organelles. The roles of such AQPs have not yet been established. They will be clues to clarify the mechanisms of water and small solutes movements inside the cell. Recently, a new AQP subfamily has been identified with highly deviated asparagine-proline-alanine boxes, signature sequences for AQP. With limited homology less than 20%, this subfamily will be a superfamily of AQPs. Accordingly, it was tentatively named "superaquaporin subfamily," which is so far only present in multicellular organisms including plants, insects, nematodes, and vertebrates. Some superaquaporins are functionally water channels and localized intracellularly. AQP11, one of the two superaquaporins in mammals, has been shown to be important for the development of the proximal tubule as its disruption produced neonatally fatal polycystic kidneys in mice. Hence, recent identification of intracellular AQPs will open new areas of research on cell biology and expand the scope of AQPs.     

Aquaporins: Unexpected actors in autoimmune diseases

Aquaporins (AQPs), transmembrane proteins allowing the passage of water and sometimes other small solutes and molecules, are involved in autoimmune diseases including neuromyelitis optica, Sjögren's syndrome and rheumatoid arthritis. Both autoantibodies against AQPs and altered expression and/or trafficking of AQPs in various tissue cell types as well as inflammatory cells are playing key roles in pathogenesis of autoimmune diseases. Detection of autoantibodies against AQP4 in the central nervous system has paved the way for a deeper understanding in disease pathophysiology as well as enabling diagnosis. This review provides a comprehensive summary of the roles of AQPs in autoimmune diseases.     

Genetic variation in human aquaporins and effects on phenotypes of water homeostasis

Aquaporins (AQPs) are critical for the transport of water and small solutes. The 13 known human AQPs are divided into those that transport only water molecules, the "orthodox" AQPs, and those that transport glycerol and small solutes in addition to water, the aquaglyceroporins. In humans, genetic variation in AQPs can cause phenotypes of abnormal water homeostasis. Cellular and human studies of naturally-occurring and synthetic mutations have provided insight into the biology and phenotypes of these variants. Many AQPs have not been well-characterized in terms of the effect of genetic variation on protein function and clinical phenotype. In this review, we discuss functional features in human AQPs and summarize previous studies of naturally-occurring variants. We focus on nonsynonymous mutations since they typically have the greatest effect on function. We develop a map of AQP variation and functional features and examine uncharacterized variants by sequence and structure analysis. We find that variation has been studied relative to the AQP pore, terminal domains, and sites critical to posttranslational modifications. Finally, we propose possible variant-based phenotypes for further research. Other open questions relate to the discovery of novel AQP gene variants as well as their functions and phenotypes.     

Immunolocalization of water channel aquaporins in human knee articular cartilage with intact and early degenerative regions

Aquaporins (AQPs), a family of water channel proteins expressed in various cells and tissues, serve as physiological pathways of water and small solute transport. Articular cartilage is avascular tissue with unique biomechanical structure, a major component of which is “water”. Our objective is to investigate the immunolocalization and expression pattern changes of AQPs in articular cartilage with normal and early degenerative regions in the human knee joint, which is the joint most commonly involved in osteoarthritis (OA). Two isoforms (AQPs 1 and 3) of AQPs were examined by immunohistochemical analyses using isoform-specific antibodies with cartilage samples from OA patients undergoing total knee arthroplasty. AQP 1 and AQP 3 were expressed in human knee articular cartilage and were localized in chondrocytes, both in the intact and early degenerative cartilage regions. Compared to the intact cartilage, both AQP 1 and AQP 3 immunopositive cells were observed at the damaged surface area in the degenerative region. These findings suggest that these AQPs play roles in metabolic water regulation in articular cartilage of load bearing joints and that they are responsible for OA onset.     

Aquaporins and cell migration

Aquaporin (AQP) water channels are expressed primarily in cell plasma membranes. In this paper, we review recent evidence that AQPs facilitate cell migration. AQP-dependent cell migration has been found in a variety of cell types in vitro and in mice in vivo. AQP1 deletion reduces endothelial cell migration, limiting tumor angiogenesis and growth. AQP4 deletion slows the migration of reactive astrocytes, impairing glial scarring after brain stab injury. AQP1-expressing tumor cells have enhanced metastatic potential and local infiltration. Impaired cell migration has also been seen in AQP1-deficient proximal tubule epithelial cells, and AQP3-deficient corneal epithelial cells, enterocytes, and skin keratinocytes. The mechanisms by which AQPs enhance cell migration are under investigation. We propose that, as a consequence of actin polymerization/depolymerization and transmembrane ionic fluxes, the cytoplasm adjacent to the leading edge of migrating cells undergoes rapid changes in osmolality. AQPs could thus facilitate osmotic water flow across the plasma membrane in cell protrusions that form during migration. AQP-dependent cell migration has potentially broad implications in angiogenesis, tumor metastasis, wound healing, glial scarring, and other events requiring rapid, directed cell movement. AQP inhibitors may thus have therapeutic potential in modulating these events, such as slowing tumor growth and spread, and reducing glial scarring after injury to allow neuronal regeneration.     

Brain volume regulation: osmolytes and aquaporin perspectives

Cerebral water control is critical to maintain neuronal excitability, and to prevent injuries derived from brain swelling or shrinkage. The influence of aquaporins (AQPs) in the balance of water distribution between intracranial compartments is getting much experimental support. The importance of AQPs in fluid clearance during vasogenic brain edema seems well established but their role in cytotoxic swelling and in brain cell shrinkage is not known in detail. The main AQPs function as water channels anticipates their influence on cell volume changes as well as on the mechanisms of volume recovery, which include notably the osmolyte translocation across the cell membrane. Osmolyte fluxes permit the reestablishment of an osmotic balance and volume recovery in anisosmotic-elicited cell volume changes, but are also causal factors per se of brain cell swelling or shrinkage in pathological situations. This review aims to inform on the so far described functional interactions between AQPs and osmolyte fluxes and their volume-sensitive pathways. It also points to the coincidence of AQPs and activation of osmolyte fluxes in physiological and pathological conditions and to the importance of finding possible functional links between these two events, thus enlarging the possibilities via AQP manipulations, to prevent the adverse consequences of cell volume changes in brain.