水通道蛋白1在哺乳动物体内的分布及功能

水通道蛋白1(aquaporins1,AQP1)是参与水分子跨膜转运的重要膜通道蛋白家族成员之一,广泛分布于各组织中,在机体物质代谢和水平衡中起着重要的作用。本文就AQP1在哺乳动物各组织中的表达和分布及其参与脑脊液的产生、细胞生物学特性的调节和感觉传导等方面相关功能的研究现况和进展作一综述。     

survivin与肿瘤细胞凋亡

凋亡抑制蛋白 (ｉｎｈｉｂｉｔｏｒｏｆａｐｏｐｔｏｓｉｓｐｒｏｔｅｉｎ ,ＩＡＰ)是抑制细胞凋亡的重要成分。ｓｕｒｖｉｖｉｎ是最近新发现的一种ＩＡＰ家族成员之一。有证据表明 ,ｓｕｒｖｉｖｉｎ在大多数肿瘤中有表达 ,但在成人终末分化组织一般不表达或低表达。本文对ｓｕｒｖｉｖｉｎ的结构和功能、组织分布、抗凋亡的机制 ,以及与对恶性肿瘤诊治的价值作一综述。一、ｓｕｒｖｉｖｉｎ的结构和功能第一个ＩＡＰ蛋白是由Ｍｉｌｌｅｒ实验室首先在杆状病毒中发现的。以后又发现了一系列ＩＡＰ蛋白。ＩＡＰ家族蛋白包含 2个或 3个串联…     

尿素通道蛋白的研究进展

尿素通道蛋白是转运尿素的跨膜蛋白 ,目前已克隆出的尿素通道蛋白包括两个家族。UT A家族有 5个亚型 ,主要分布在肾脏 ,UT B家族分布广泛 ,主要分布在红细胞膜和肾直小血管降支。尿素通道蛋白在肾脏尿浓缩过程中起重要作用 ,其表达可受加压素、血浆渗透压和饮食蛋白量的调节。     

水通道蛋白4在大鼠胃内的分布

水通道蛋白 1(Aquaporin 1,AQP1)首次被克隆[1 ] 并证实其对水分子具有高度选择性和通透性 ,这为解析水分子快速透过以脂质双层分子为骨架基础 ,并具有亲脂性的细胞膜提供了结构基础。胃的生理功能之一是对水分的吸收和分泌 ,该过程涉及大量水分子跨膜运动 ,目前对胃粘膜上AQP功能及分布研究不多 ,已有的报道多与AQP1相关 ,而水通道蛋白4 (Aquaporin 4 ,AQP4 )的生物学特点与AQP1有所不同 ,即对汞不敏感。本研究应用免疫组化法检测正常大鼠胃粘膜内AQP4分布情况 ,以推测其在胃内的生理功能。1　材料与方法1 1　实验动物与标本准备 :…     

Copines蛋白家族的研究进展

Copines蛋白家族是新近发现的一类分布广泛、进化保守的Ca2 依赖性磷脂结合蛋白,它们的结构特征为:N端有2个C2结构域,与突触结合蛋白(synaptotagmin)和蛋白激酶C的C2结构域不但高度同源,而且同样具有Ca2 依赖性的磷脂结合功能;C端有1个A结构域,与整合蛋白A结构域部分同源,是蛋白与蛋白相互作用的结构域。近年来研究表明,Copines家族成员与细胞的膜转运、胞内信号转导、肿瘤发生等重大生物过程都密切相关。     

丹参酮ⅡA激活Nrf2/Nox4通路减轻脂多糖诱导的小鼠肺炎和纤维化

目的研究丹参酮ⅡA(Tan ⅡA)对脂多糖诱导小鼠肺炎和纤维化影响,探讨其潜在的作用机制。方法30只8周龄雄性C57BL/6小鼠,随机分成对照组、脂多糖(LPS)组和LPS+Tan ⅡA组。采用尾静脉注射LPS制作小鼠肺炎和纤维化动物模型,术后给予Tan ⅡA干预,每日一次,连续2周,实验第4周处死所有小鼠,收集血清和肺组织标本。采用HE染色检测肺组织炎症改变,Masson染色观察肺组织纤维化程度,ELISA检测血清IL-1β、TNF-α和IL-10蛋白表达,采用Western blot技术检测肺组织Nrf2、Nox4、Nqo1和Ho-1蛋白表达。结果与对照组相比,LPS组小鼠肺脏重量、肺脏/体重比显著增加,肺组织水肿、炎细胞浸润和纤维化明显加重,血清促炎蛋白IL-1β、TNF-α显著升高,抑炎蛋白IL-10表达下降(P<0.05)。Tan ⅡA处理显著减轻LPS导致的小鼠肺脏重量、肺脏/体重比,减轻肺水肿、炎细胞浸润和纤维化,减低血清IL-1β、TNF-α表达水平,升高IL-10表达水平。此外,Nrf2和Nox4蛋白表达水平LPS组高于对照组,Nqo1和Ho-1蛋白表达水平低于对照组,而Tan ⅡA处理可以上调Nrf2、Nqo1和Ho-1蛋白,降低Nox4蛋白表达水平(P<0.05)。结论Tan ⅡA减轻LPS诱发的小鼠炎症和纤维化,与激活Nrf2/Nox4通路相关。     

BCL-2家族与线粒体对细胞凋亡的调控

线粒体是细胞凋亡调控的中心环节, 它通过释放膜间隙中的促凋亡蛋白(细胞色素C、Smac/DIABLO、AIF和en donucleaseG等)来起作用。线粒体膜间隙 (IMS)蛋白的释放是由BCL-2家族蛋白调控的。BCL-2家族蛋白能够诱导线粒体通透性转变孔道 (PT孔道 )的开放, 导致细胞凋亡。关于PT孔道开启的机制是近年来研究的一个热点。本文综述了近年来有关线粒体与BCL-2家族对细胞凋亡调控的研究进展。     

水孔蛋白的功能及与疾病的关系

水孔蛋白普遍存在于微生物、植物及动物界。哺乳动物体内已发现有 11种水孔蛋白。根据基因序列同源性、种系发育比较及通透特性可将水孔蛋白分为两类 ,即传统意义上的水孔蛋白以及甘油水孔蛋白。各种组织中都有水孔蛋白存在 ,但它们所担当的具体生理功能尚有区别。有些水孔蛋白表达异常还与某些疾病相关 ,如AQP2基因突变可导致肾性尿崩症 ,AQPap表达异常与肥胖、胰岛素抵抗关系密切。     

CD151在肿瘤发生中的作用机制及其潜在的治疗意义

四跨膜蛋白家族(transmenbrane 4 super family,TM4SF)成员也称tetraspanin,是一类存在于真核多细胞生物细胞膜上的蛋白家族,相对分子质量为(21 ～28) ×103.其结构为横跨四次细胞膜的Ⅲ型膜糖蛋白复合体,含有4个高度疏水的跨膜结构域.胞质区为短的N2末端和稍长的C2末端,并在4个跨膜结构域之间形成2个一大一小的细胞外环.其中大环及其跨膜区构成了四跨膜蛋白家族的结构和功能特异性并在调整其与其他膜蛋白(如整合素、Ig蛋白超家族等)的相互作用上发挥重要作用.     

磷脂酶A_2激活在受体信号转导系统转变中的作用

与鸟核苷酸结合调节蛋白(G蛋白)相偶联的、具有7个跨膜区段的膜表面受体很多,但它们的信号转导系统只有两个:受体-G蛋白-腺苷酸环化酶(AC)系统和受体-G蛋白-磷脂酰肌醇(PI)系统。本研究以具有M_2亚型胆碱能受体(M_2受体)的人胚肺成纤维细胞证实,在激动剂氨甲酰胆碱(CCh)长时间作用下,原来与     

Role of aquaporins in lung liquid physiology

Aquaporins (AQPs) are small, integral membrane proteins that facilitate water transport across cell membranes in response to osmotic gradients. Water transport across epithelia and endothelia in the peripheral lung and airways occurs during airway hydration, alveolar fluid transport and submucosal gland secretion. Several AQPs are expressed in the lung and airways: AQP1 in microvascular endothelia, AQP3 and AQP4 in airway epithelia, and AQP5 in type I alveolar epithelial cells, submucosal gland acini, and a subset of airway epithelial cells. Phenotype analysis of transgenic knockout mice lacking AQPs has defined their roles in the lung and airways. AQP1 and AQP5 provide the principal route for osmotically driven water transport between airspace and capillary compartments; however, alveolar fluid clearance in the neonatal and adult lung is not affected by their deletion, nor is lung fluid accumulation in experimental models of lung injury. In the airways, though AQP3 and AQP4 facilitate osmotic water transport, their deletion does not impair airway hydration, regulation of airway surface liquid, or fluid absorption. In contrast to these negative findings, AQP5 deletion in submucosal glands reduced fluid secretion by >50%. The substantially slower fluid transport in the lung compared to renal and secretory epithelia probably accounts for the lack of functional significance of AQPs in the lung and airways. Recent data outside of the lung implicating the involvement of AQPs in cell migration and proliferation suggests possible new roles for lung AQPs to be explored.     

Use of aquaporins 1 and 5 levels as a diagnostic marker in mild-to-moderate adult-onset asthma

Characteristic features of asthma include airway inflammation and hyperactivity, mucus hypersecretion, mucosal edema, and airway remodeling. These features could be due to pathological water transport across pulmonary epithelia and aquaporins (AQPs) have recently been isolated as key proteins in fluid transportation in the human respiratory tract. We aimed to evaluate the role of aquaporins in the pathogenesis of asthma and their possible use a diagnostic marker of the disease. A total of 110 hospitalized and outpatients with mild to moderate adult-onset asthma were invited to participate in this study and 34 submitted an induced sputum sample adequate for analysis. The amount of AQP1, AQP5 and MUC5AC were measured with ELISA assay. The amount of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17 in both serum and sputum were measured with Cytometry Bead Array (CBA kit). Our results suggest that sputum AQP5, AQP1 and MUC5AC are all in a good correlation (r=0.498 between AQP5 and AQP1, r=0.529 and r=0.661 between MUC5AC and AQP5 or AQP1, respectively, all P<0.05). The AUC value for AQP1 and AQP5 to diagnose asthma were 0.729 and 0.745, respectively. In conclusion, water homeostasis plays an important role in maintaining adequate fluid transportation within the lung and is involved in the pathogenesis of asthma. Our results suggest that AQP may influence pulmonary physiology that their dysfunction can contribute to pulmonary pathogenesis, such as asthma. Moreover, their quantification could serve as biomarkers for the diagnosis of asthma.     

Decreased expression of aquaporin (AQP)1 and AQP5 in mouse lung after acute viral infection

Intratracheal infection of mice with adenovirus is associated with subsequent pulmonary inflammation and edema. Water movement through the air space-capillary barrier in the distal lung is facilitated by aquaporins (AQPs). To investigate the possibility that distal lung AQPs undergo altered regulation under conditions of aberrant fluid handling in the lung, we analyzed messenger RNA (mRNA) and protein expression of AQPs 1 and 5 in the lungs of mice 7 and 14 d after infection with adenovirus. Here, we demonstrate that AQP1 and AQP5 show decreased expression following adenoviral infection. Northern blot analysis showed significantly decreased mRNA levels of AQP1, which is expressed in the capillary endothelium, and AQP5, which is expressed in alveolar epithelium, in the lungs of mice both 7 and 14 d after infection. Immunoblotting studies demonstrated significantly reduced levels of AQP1 and AQP5 protein after infection as well. In addition, mRNA expression of the alpha subunit of the epithelial sodium channel was reduced in the lungs of mice 7 and 14 d after adenoviral infection. In contrast, mRNA expression of the alpha1 subunit of the Na,K-adenosine triphosphatase in the lung was unaltered. Immunohistochemical analysis demonstrated that the decreases in AQP1 and AQP5 expression were not localized to regions of overt inflammation but were found throughout the lung. Thus, this study provides the first report of AQP gene regulation in an in vivo model of pulmonary inflammation and edema. Decreased AQP1 and AQP5 levels during adenoviral infection suggest a role for AQP1 and AQP5 in the abnormal fluid fluxes detected during pulmonary inflammation.     

Immunolocalization of water channel aquaporins in the nasal olfactory mucosa

Aquaporins (AQPs), membrane water channel proteins expressed in various tissues and organs, serve in the transfer of water and small solutes across the membrane. We raised antibodies to AQPs using isoform-specific synthetic peptides and surveyed their expression in the rat nasal olfactory and respiratory mucosae. AQP1, AQP3, AQP4, and AQP5 were detected by immunohistochemical and immunoblotting analyses. AQP1 was expressed in the endothelial cells of blood vessels and the surrounding connective tissue cells in the olfactory and respiratory mucosae. AQP1 may be involved in water transfer across the blood vessel wall. In the olfactory epithelium, no AQP was detected in the olfactory sensory cells. Instead, AQP3 was abundant in the olfactory epithelium, where it was localized in the supporting cells and basal cells. Expression of AQP3 was mostly restricted to the basal cells in the respiratory epithelium. In marked contrast, AQP4 was abundant in the respiratory epithelium, but its abundance was limited to the basal cells in the olfactory epithelium. In the Bowman's gland, AQP5 was localized in the apical membrane in the secretory acinar cells, whereas AQP3 and AQP4 were found in the basolateral membrane. Similar localization was seen in its duct cells. These results showed a distinct localization pattern for AQPs in the olfactory epithelium. AQP3 and AQP4 in the supporting cells and basal cells may play an important role in generating and maintaining the specific microenvironment around the olfactory sensory cells. AQP3, AQP4, and AQP5 in the Bowman's gland may serve in the secretion to generate the microenvironment at the apical surface of the olfactory dendrites for odorant reception.     

Tanshinone IIA ameliorates seawater exposure-induced lung injury by inhibiting aquaporins (AQP) 1 and AQP5 expression in lung

Aquaporins (AQPs), a family of transmembrane water channels, mediate physiological response to changes of fluid volume and osmolarity. It is still unknown what role of AQPs plays in seawater drowning-induced acute lung injury (ALI) and whether pharmacologic modulation of AQPs could alleviate the severity of ALI caused by seawater aspiration. In our study, the results from RT-PCR and Western blotting showed that intratracheal installation of seawater up-regulated the mRNA and protein levels of AQP1 and AQP5 in lung tissues. Furthermore, we found that treatment of tanshinone IIA (TIIA, one of the main active components from Chinese herb Danshen) significantly reduced the elevation of AQP1 and AQP5 expression induced by seawater in rats, A549 cells and primary alveolar type II cells. Treatment of TIIA also improved lung histopathologic changes and blood-gas indices, and reduced lung edema and vascular leakage. These findings demonstrated that AQP1 and AQP5 might play an important role in the development of lung edema and lung injury, and that treatment with TIIA could significantly alleviate seawater exposure-induced ALI, which was probably through the inhibition of AQP1 and AQP5 over-expression in lungs.     

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.     

Aquaporin-1 in breast cancer

The canonical function of aquaporin (AQP) water channels is to facilitate passive transport of water across cellular membranes making them essential in the regulation of body water homeostasis. Moreover, AQPs, including AQP1, have been found to be overexpressed in multiple cancer types, including breast cancer, where AQP1 overexpression is associated with poor prognosis. AQPs have been shown to affect cellular processes associated with cancer progression and spread including cell migration, angiogenesis, and proliferation. Moreover, AQPs can regulate levels of adhesion proteins at cell–cell junctions, a regulatory role, which is still largely unexplored in cancer. Understanding the molecular mechanisms of how AQP1 contributes to breast cancer progression and metastatic processes is essential to establish AQP1 as a biomarker and to develop targeted anticancer treatments for breast cancer patients. This mini-review focuses on the role of AQP1 in breast cancer.     

Upregulation of AQP3 and AQP5 induced by dexamethasone and ambroxol in A549 cells

Aquaporins (AQPs) are membrane channel proteins that play roles in the regulation of water permeability in many tissues. AQP1 and AQP5 expressed in lung provide the principal route for osmotically driven water transport. In the airways, AQP3 and AQP4 facilitate water transport. Dexamethasone and ambroxol are often used to treat patients with pulmonary diseases accompanied by airway hypersecretion. The role of AQPs in these effective treatments has not been addressed. In this study, we analyzed the expression of AQPs in a human airway epithelial cell line (A549 cells) and showed that AQP3 and 5, but not AQP1 and 4, were expressed in A549 cells. Both dexamethasone and ambroxol stimulated the expression of AQP3 and 5 at the mRNA and protein levels. The data suggest potential roles of AQP3 and 5 in the regulation of airway hypersecretion, perhaps ultimately providing a target for treating such diseases.     

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.     

AQP1 mediates water transport in the carotid body

In this study, we explored the presence of aquaporins (AQPs), a family of membrane water channel proteins, in carotid body (CB) type I chemoreceptor cells. The CB is a polymodal chemoreceptor whose major function is to detect changes in arterial O₂ tension to elicit hyperventilation during hypoxia. The CB has also been proposed to function as a systemic osmoreceptor, thus we hypothesized that the presence of AQPs in type I cell membrane may confer higher sensitivity to osmolarity changes and hence accelerate the activation of chemoreceptor cells. We detected the expression of AQP1, AQP7, and AQP8 in the CB and confirmed the location of AQP1 in type I cells. We have also shown that inhibition of AQP1 expression clearly reduced type I cell swelling after a hyposmotic shock, demonstrating that AQP1 has a major contribution in transmembrane water movement in these chemoreceptor cells. Interestingly, CB AQP1 expression levels change during postnatal development, increasing during the first postnatal weeks as the organ matures. In conclusion, in this study, we report the novel observation that AQPs are expressed in the CB. We also show that AQP1 mediates water transport across the cell membrane of type I cells, supporting the contribution of this protein to the osmoreception function of the CB.