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Sample records for brain aquaporin aqp4

  1. Glial-conditional deletion of aquaporin-4 (Aqp4) reduces blood–brain water uptake and confers barrier function on perivascular astrocyte endfeet

    OpenAIRE

    Haj-Yasein, Nadia Nabil; Vindedal, Gry Fluge; Eilert-Olsen, Martine; Gundersen, Georg Andreas; Skare, Øivind; Laake, Petter; Klungland, Arne; Thorén, Anna Elisabeth; Burkhardt, John Michael; Ottersen, Ole Petter; Nagelhus, Erlend Arnulf

    2011-01-01

    Tissue- and cell-specific deletion of the Aqp4 gene is required to differentiate between the numerous pools of aquaporin-4 (AQP4) water channels. A glial-conditional Aqp4 knockout mouse line was generated to resolve whether astroglial AQP4 controls water exchange across the blood–brain interface. The conditional knockout was driven by the glial fibrillary acidic protein promoter. Brains from conditional Aqp4 knockouts were devoid of AQP4 as assessed by Western blots, ruling out the presence o...

  2. Aquaporin-4 autoantibodies in Neuromyelitis Optica: AQP4 isoform-dependent sensitivity and specificity.

    Directory of Open Access Journals (Sweden)

    Francesco Pisani

    Full Text Available Neuromyelitis Optica (NMO is an autoimmune demyelinating disease, characterized by the presence of autoantibody (NMO-IgG to Aquaporin-4 (AQP4. NMO-IgG identification supports NMO diagnosis and several diagnostic tests have been developed, but their sensitivity is too variable, and some assay show low sensitivity. This impairs correct diagnosis of NMO. By cell based assay (CBA we here evaluate the efficacy of different strategies to express AQP4 in mammalian cells in terms of: a AQP4 translation initiation signals; b AQP4 isoforms (M1 and M23 and fluorescent tag position; c NMO serum concentration and AQP4 degradation. Our results demonstrate that when using AQP4-M1, the nucleotide in position -3 of the AUG greatly affects the AQP4-M1/M23 protein ratio, NMO-IgG binding, and consequently test sensitivity. Test sensitivity was highest with M23 expressing cells (97.5% and only 27.5% with AQP4-M1. The fluorescent tag added to the N-terminus of AQP4-M23 considerably affected the NMO-IgG binding, and test sensitivity, due to disruption of AQP4 suprastructures. Furthermore, sera used at high concentration resulted in AQP4 degradation which affected test sensitivity. To further evaluate the reliability of the M23 based CBA test, samples of one NMO patient collected during about 2 years clinical follow-up were tested. The results of serum titer correlated with disease activity and treatment response. In conclusion, we provide a molecular explanation for the contrasting CBA test data reported and suggest the use of M23 with a C-terminus fluorescent tag as the proper test for NMO diagnosis.

  3. 人脑挫裂伤早期周围组织AQP4表达及血脑屏障超微结构观察%The expression of aquaporin-4 and the ultramicrostructure change of blood-brain barrier in human contusion brain tissue early after injury

    Institute of Scientific and Technical Information of China (English)

    李新军; 韩杨云; 徐宏; 孙中书; 周增俊; 龙晓东; 杨与敏; 邹林波

    2012-01-01

    Objective To observe the expression of aquaporin 4(AQP4) and the ultramicrostructure change of blood-brain barrier in human contusion brain tissue at different time points and investigate the mechanism of brain edema formation. Methods 60 cases brain contusion tissue (observation group) and 10 cases normal non-functional brain tissues (control group) were collected. The expression of AQP4 at different time point was detected by immunity histochemistry and image analytical technique at 2 ~72 h after injury,brain water contents, BBB index and ultramicrostructure were observed at the same time point. Results Compared with the normal control group, AQP4 expression increased in observation group at 2 h (P<0.05), obviously increased at 6 h ,8 h J2 h (P<0.01), reached peak at 24-72 h(P <0.01). The change of AQP4 expression and brain water content had same tendency (r = 0. 912, P < 0.01) which also was displayed between BBB index and brain water content(r =0.877,P <0.01). The change of AQP4 expression and BBB index had significant positive correlation(r =0.908, P <0.01). Blood-brain barrier structure changed early after injury, and then destroyed, severely damaged at 24 h, 72 h. Conclusions The expression of AQP4 and the permeability of BBB significantly increased after brain contusion which suggesting AQP4 may play an important role in the brain edema formation after brain contusion.%目的 观察人脑挫裂伤后AQP4和血脑屏障超微结构在脑水肿形成中不同时间点的变化特征,探讨脑水肿的形成机制.方法 取脑挫裂伤区组织标本60例(观察组),10例非功能区正常脑组织标本(对照组).采用免疫组化和图像分析技术测定正常组及观察组伤后2~72 h相应时间点水肿区AQP4的表达水平,同时观察脑水肿含水量,血脑屏障指数,血脑屏障超微结构的变化.结果 与正常组相比较,脑挫裂伤组在伤后2h后AQP4表达开始增加(P<0.05),6h、8h、12h明显增加(P<0.01),24~72 h

  4. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HuaHu; Wei-PingZhang; LeiZhang; ZhongChen; Er-QingWei

    2004-01-01

    Aquaporin-4 (AQP4) is one of the aquaporins (AQPs), a water channel family. In the brain, AQP4 is expressed in astroeyte foot processes, and plays an important role in water homeostasis and in the formation of brain edema. In our study, AQP4 expression in human brain specimens from patients with traumatic brain injury or different brain tumors was detected

  5. Effect of progesterone intervention on the dynamic changes of AQP-4 in hypoxic-ischaemic brain damage.

    Science.gov (United States)

    Li, Xiaojuan; Bai, Ruiying; Zhang, Junhe; Wang, Xiaoyin

    2015-01-01

    To observe the effect of progesterone (PROG) on blood-brain barrier (BBB) permeability, brain tissue water content and dynamic changes of aquaporin-4 (AQP-4) in neonatal rats with hypoxic-ischaemic brain damage (HIBD). 72 neonatal Wistar rats, aged 7 days old, were randomly divided into control, hypoxic-ischaemic (6, 24 and 72 h, and 7 d subgroups) and drug groups (6, 24 and 72 h, and 7 d subgroups). The HIBD animal model was established. BBB was detected via an Evans blue tracer. Brain water content was determined by the dry/wet method. The AQP-4 expression in the cerebral cortex was observed through immunohistochemistry and Western blot. BBB permeability in the cerebral cortex of the neonatal rats, brain water content and AQP-4 expression in the hypoxia-ischaemia group were significantly higher than those of the control group after hypoxia for 6 h (P permeability in the cerebral cortex of the neonatal rats, brain water content and AQP-4 expression in the drug group were significantly lower than those of the hypoxia-ischaemia group after hypoxia for 6, 24 and 72 h (P permeability and BBB expression were positively correlated with the AQP-4 expression. In conclusion, PROG protects the brain of HIBD neonatal rats by alleviating the damage of BBB and cerebral oedema. The protective effect of PROG may be related to the down-regulation of AQP-4 expression in the cerebral cortex of neonatal rats. PMID:26770503

  6. PHYSIOLOGICAL ROLES OF AQUAPORIN-4 IN BRAIN

    OpenAIRE

    Nagelhus, Erlend A.; Ottersen, Ole P.

    2013-01-01

    Aquaporin-4 (AQP4) is one of the most abundant molecules in the brain and is particularly prevalent in astrocytic membranes at the blood-brain and brain-liquor interfaces. While AQP4 has been implicated in a number of pathophysiological processes, its role in brain physiology has remained elusive. Only recently has evidence accumulated to suggest that AQP4 is involved in such diverse functions as regulation of extracellular space volume, potassium buffering, cerebrospinal fluid circulation, i...

  7. Atorvastatin ameliorates early brain injury after subarachnoid hemorrhage via inhibition of AQP4 expression in rabbits.

    Science.gov (United States)

    Chen, Jun-Hui; Yang, Li-Kun; Chen, Lei; Wang, Yu-Hai; Wu, Yun; Jiang, Bing-Jie; Zhu, Jie; Li, Pei-Pei

    2016-04-01

    The therapeutic effects of atorvastatin on early brain injury (EBI), cerebral edema and its association with aquaporin 4 (AQP4) were studied in rabbits after subarachnoid hemorrhage (SAH) using western blot analysis and the dry-wet method. Seventy-two healthy male New Zealand rabbits weighing between 2.5 and 3.2 kg were randomly divided into three groups: the SAH group (n=24), sham-operated group (n=24) and the SAH + atorvastatin group (n=24). A double SAH model was employed. The sham-operated group were injected with the same dose of saline solution, the SAH + atorvastatin group received atorvastatin 20 mg/kg/day after SAH. All rabbit brain samples were taken at 72 h after the SAH model was established successfully. Brain edema was detected using the dry-wet method after experimental SAH was induced; AQP4 and caspase-3 expression was measured by western blot analysis, and neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) staining at 72 h after SAH. The results indicated that brain edema and injury appeared soon after SAH, while brain edema and EBI were ameliorated and increased behavior scores were noted after prophylactic use of atorvastatin. Compared with the SAH group, the level of AQP4 and the cerebral content of water was significantly decreased (Patorvastatin, and TUNEL staining and studying the expression of caspase-3 showed that the apoptosis of neurons was reduced markedly both in the hippocampus and brain cortex by atorvastatin. The results suggest that atorvastatin ameliorated brain edema and EBI after SAH, which was related to its inhibition of AQP4 expression. Our findings provide evidence that atorvastatin is an effective and well-tolerated approach for treating SAH in various clinical settings. PMID:26935263

  8. [Roles of Aquaporins in Brain Disorders].

    Science.gov (United States)

    Yasui, Masato

    2015-06-01

    Aquaporin (AQP) is a water channel protein that is expressed in the cell membranes. AQPs are related to several kinds of human diseases such as cataract. In the mammalian central nervous system (CNS), AQP4 is specifically expressed in the astrocyte membranes lining the perivascular and periventricular structures. AQP4 plays a role in the development of brain edema associated with certain brain disorders. Neuromyelitis optica (NMO) is a demyelinating disorder, and patients with NMO develop autoimmune antibodies against AQP4 in their serum. Therefore, AQP4 is involved in NMO pathogenesis. A new concept referred to as "glymphatic pathway" has been recently proposed to explain the lymphatic system in the CNS. Dysfunction of the "glymphatic pathway" may cause several neurodegenerative diseases and mood disorders. Importantly, AQP4 may play a role in the "glymphatic pathway". Further investigation of AQP4 in CNS disorders is necessary, and a new drug against AQP4 is expected. PMID:26062588

  9. New isoforms of rat Aquaporin-4

    DEFF Research Database (Denmark)

    Moe, Svein Erik; Sorbo, Jan Gunnar; Søgaard, Rikke;

    2008-01-01

    Aquaporin-4 (AQP4) is a brain aquaporin implicated in the pathophysiology of numerous clinical conditions including brain edema. Here we show that rat AQP4 has six cDNA isoforms, formed by alternative splicing. These are named AQP4a-f, where AQP4a and AQP4c correspond to the two classical M1 and M...

  10. RNAi沉默AQP-4技术治疗胶质瘤性脑水肿的实验研究%An experimental study of the treatment of glioma brain edema by RNAi silencing AQP-4

    Institute of Scientific and Technical Information of China (English)

    梁冰; 刘晓智; 张赛; 苏治国; 陈镭; 姜忠敏; 于士柱; 刘振林

    2012-01-01

    目的 应用RNA干扰(RNAi)技术靶向沉默胶质瘤内水通道蛋白4(AQP -4)的表达,观察其对胶质瘤源性脑水肿的治疗效果.方法 构建靶向AQP-4的siRNA质粒,免疫荧光化学方法检测其对C6细胞AQP-4的沉默效果;建立SD大鼠颅内C6胶质瘤模型,分对照组、空载组、无义序列组和siRNA组;聚合酶链式反应和蛋白印迹方法分别检测第3、6、9、12天AQP-4的mRNA和蛋白水平;干/湿比重法和Evans蓝测定法检测不同时相脑组织含水量和血脑屏障通透性改变;比较动物生存期.结果 siRNA可沉默AQP-4表达;siRNA组脑组织水含量和血脑屏障通透性均明显低于对照组、空载组和无义序列组,动物生存期最长.结论 靶向AQP-4的RNAi技术可在一定程度上减轻胶质瘤性脑水肿的发生和发展,为胶质瘤脑水肿提供了一种新的治疗策略选择.%Objective To observe the treatment effect on glioma cerebral edema by RNA interference ( RNAi ) technology silencing aquaporin 4 ( AQP-4 ) expression.Methods The siRNA plasmid targeting AQP-4 was constructed,and transfected into C6 glioma cells by liposome.Immunofluorescence assay was used to verify the silencing effect of AQP-4.The intracal C6 glioma model was established in SD rats,and four sub-groups,control group,empty vector transfected group,nonsense group and AQP-4 siRNA treated group,were divided.The AQP-4 mRNA and protein levels,in rats model brain tissue on 3,6,9,and 12 day,were detected by RT-PCR and Western Blot.Moreover,dry/wet weight method and evans blue assay were used to detect the brain water content and blood-brain barrier permeability changes.Then the animal survival was compared.Results siRNA can effectively reduce AQP -4 expression in C6 glioma cells.Compared with the control and empty vector transfected group in vivo,AQP-4 siRNA treatment group can effectively reduce AQP-4 mRNA and protein level,decrease brain water content,and reduce blood-brain barrier

  11. AQP4 expression and its relationship with brain edema after gamma kife radiosurgery in rats

    International Nuclear Information System (INIS)

    Objective: To explore AQP4 expression and its relationship with brain edema after gamma knife radiosurgery (GKRS) in rats. Methods: Wistar rats were divided into two groups-the control group and experimental group. The experimental group model was established by radiating rat left rotral caudate nucleus with GKRS (100 Gy, 4 mm), and was examinded at interval times of 1 d, 3 d, 7 d, 15 d, 30 d and 45 d. Brain water content (BWC) was determined by wet-dry weighing method. AQP4 expression on mRNA and protein were measured by immunohistochemistry (ICH) and in situ hybridization (ISH). Results: In control group, AQP4 protein and its mRNA were expressed in subpial astrocytes, choroid plexus, ependyma and perivascular astrocytes. After GKRS, AQP4 protein and its mRNA in these sites were enhanced, and became most remarkable at 30 d. The positive corrlationship was showed between AQP4 and its mRNA, and AQP4 and BWC. Conclusions: AQP4 protein and its mRNA can be induced in some brain zone after irradiating rat left rotral caudate nucleus with GKRS. The increased expression of AQP4 and its mRNA may play a role in the ocurrence or development of brain edema after GKRS. (authors)

  12. Aquaporin-4 and ischemic brain edema

    Institute of Scientific and Technical Information of China (English)

    Saihong Dun; Yang Guo

    2007-01-01

    OBJECTIVE: To investigate the relationship of aquaporin 4 (AQP4) and brain edema.DATA SOURCES: Using the terms of "aquaporin-4, brain edema", we searched PubMed database to identify studies published from January 1997 to April 2006 in the English languages. Meanwhile, we also searched China National Knowledge Infrastructure (CNKI) for related studies.STUDY SELECTION: The collected data were selected firstly. Studies on AQP4 and brain edema were chosen and their full-texts were searched for, and those with repetitive or review studies were excluded.DATA EXTRACTION: Totally 146 related studies were collected, 42 of them were involved and the other 104 studies were used for reading reference data.DATA SYNTHESIS: AQP4 is a selective water permeable integral membrane protein. It is mainly expressed in astrocytes and ependymocyte, and is the important structural basis for water regulation and transportation between glial cells and cerebrospinal fluid or vessels. Phosphorylation is involved in the regulation of AQP4.AQP4 participates in the formation of brain edema caused by various factors. Studies on the structure and pathological changes of AQP4 are still in the initial stage, and the role and mechanism of AQP4 in the formation of brain edema is very unclear.CONCLUSION: AQP4 plays a critical regulating role in the formation of ischemic brain edema, but whether it is regulated by drugs lacks reliable evidence.

  13. Regulation of astrocyte glutamate transporter-1 (GLT1) and aquaporin-4 (AQP4) expression in a model of epilepsy.

    Science.gov (United States)

    Hubbard, Jacqueline A; Szu, Jenny I; Yonan, Jennifer M; Binder, Devin K

    2016-09-01

    Astrocytes regulate extracellular glutamate and water homeostasis through the astrocyte-specific membrane proteins glutamate transporter-1 (GLT1) and aquaporin-4 (AQP4), respectively. The role of astrocytes and the regulation of GLT1 and AQP4 in epilepsy are not fully understood. In this study, we investigated the expression of GLT1 and AQP4 in the intrahippocampal kainic acid (IHKA) model of temporal lobe epilepsy (TLE). We used real-time polymerase chain reaction (RT-PCR), Western blot, and immunohistochemical analysis at 1, 4, 7, and 30days after kainic acid-induced status epilepticus (SE) to determine hippocampal glial fibrillary acidic protein (GFAP, a marker for reactive astrocytes), GLT1, and AQP4 expression changes during the development of epilepsy (epileptogenesis). Following IHKA, all mice had SE and progressive increases in GFAP immunoreactivity and GFAP protein expression out to 30days post-SE. A significant initial increase in dorsal hippocampal GLT1 immunoreactivity and protein levels were observed 1day post SE and followed by a marked downregulation at 4 and 7days post SE with a return to near control levels by 30days post SE. AQP4 dorsal hippocampal protein expression was significantly downregulated at 1day post SE and was followed by a gradual return to baseline levels with a significant increase in ipsilateral protein levels by 30days post SE. Transient increases in GFAP and AQP4 mRNA were also observed. Our findings suggest that specific molecular changes in astrocyte glutamate transporters and water channels occur during epileptogenesis in this model, and suggest the novel therapeutic strategy of restoring glutamate and water homeostasis. PMID:27155358

  14. A correlative study between AQP4 expression and the manifestation of DWI after the acute ischemic brain edema in rats

    Institute of Scientific and Technical Information of China (English)

    鲁宏; 孙善全

    2003-01-01

    Objective To investigate the rule of the aquaporin-4 (AQP4) expression in acute ischemic brain edema, and to study the correlation between AQP4 expression and diffusion-weighted imaging (DWI).Methods Thirty-six Wistar rats were divided into 2 groups randomly, control group (n=12) and operation group (n=24) in which right middle cerebral artery of each animal had been occluded unilaterally (MCAO) at interval times of: 15 minutes, 30 minutes, 1 hours, 3 hours, 6 hours and 24 hours, respectively. The operation process of the control group was the same as the operation group except for the MCAO. All groups were examined using DWI. The apparent diffusion coefficient (ADC), relative density (rd) and relative area (rs) of the biggest hyperintensity signal layer on DWI were measured. After that the animals were sacrificed and perfused with the mixture solution consisting of TTC. The biggest layers of the ischemic cerebral tissues in each rat corresponding to the DWI were stained with TTC and examined with immunochemistry (△S) , in situ hybridization (α) and histology.Results There was no significant change in the control group. In the operation group, a hyperintensity signal was found in the DWI of the right MAC territory at 15 minutes after MCAO. The ADC value decreased quickly within one hour after MCAO, while the AQP4 expression, rd-DWI and rs-DWI increased rapidly during this stage. As time progressed, the ADC value decreased further to (2.1±0.6)×10-4 mm2/s at 3 hours, and then began to increase slowly till 24 hours. But the AQP4 expression (△S and α) and rd as well as the rs continuously increased slowly between 1 hour and 6 hours after MCAO, followed a peak after 6 hours. The AQP4 expression (α) showed a positive relationship with the rs-DWI, they all presented two peaks and a plateau. The corresponding sequential pathologic changes were a gradual increase of intracellular edema (within one hour), then an emergence of vasogenic edema (1-6 hours), and final

  15. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HU Hua; YAO Hong-tian; ZHANG Wei-ping; ZHANG LEI; DING Wei; ZHANG Shi-hong; CHEN Zhong; WEI Er-qing

    2005-01-01

    Objective: To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors. Methods: Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression. Results: AQP4 expression was increased from 15h to at least 8 d after injury. AQP4immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung.Conclusion: AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.

  16. Relationship between AQP4 expression and structural damage to the blood-brain barrier at early stages of traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    LU Hong; LEI Xiao-yan; HU Hui; HE Zhan-ping

    2013-01-01

    Background Although some studies have reported that aquaporin-4 (AQP4) plays an important role in the brain edema after traumatic brain injury (TBI),little is known about the AQP4 expression in the early stage of TBI,or about the correlation between the structural damage to the blood-brain barrier (BBB) and angioedema.The aim of this project was to investigate the relationship between AQP4 expression and damage to the BBB at early stages of TBI.Methods One hundred and twenty healthy adult Wistar rats were randomly divided into two greups:sham operation group (SO) and TBI group.The TBI group was divided into five sub-groups according to the different time intervals:1,3,6,12,and 24 hours.The brains of the animals were taken out at different time points after TBI to measure brain water content.The cerebral edema and BBB changes in structure were examined with an optical microscopy (OM) and transmission electron microscopy (TEM),and the IgG content and AQP4 protein expression in traumatic brain tissue were determined by means of immunohistochemistry and Western blotting.The data were analyzed with SPSS 13.0statistical software.Results In the SO greup,tissue was negative for IgG,and there were no abnormalities in brain water content or AQP4 expression.In the TBI group,brain water content significantly increased at 6 hours and peaked at 24 hours following injury.IgG expression significantly increased from 1 to 6 hours following injury,and remained at a high level at 24 hours.Pathological observation revealed BBB damage at 1 hour following injury.Angioedema appeared at 1 hour,was gradually aggravated,and became obvious at 6 hours.Intracellular edema occurred at 3 hours,with the presence of large glial cell bodies and mitochondrial swelling.These phenomena were aggravated with time and became obvious at 12 hours.In addition,microglial proliferation was visible at 24 hours.AQP4 protein expression were reduced at 1 hour,lowest at 6 hours,and began to increase at 12 hours

  17. Aquaporin-4 and traumatic brain edema

    Institute of Scientific and Technical Information of China (English)

    XU Miao; SU Wei; XU Qiu-ping

    2010-01-01

    Brain edema leading to an expansion of brain volume has a crucial impact on morbidity and mortal-ity following traumatic brain injury as it increases intracra-nial pressure, impairs cerebral perfusion and oxygenation,and contributes to additional ischemic injuries.Classically,two major types of traumatic brain edema exist: "vasogenic"and "cytotoxic/cellular".However, the cellular and molecu-lar mechanisms contributing to the development/resolution of traumatic brain edema are poorly understood and no ef-fective drugs can be used now.Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, pre-dominantly in astrocyte foot processes at the borders be-tween the brain parenchyma and major fluid compartments, including cerebrospinal fluid and blood.This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma.In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma.AQP4 has been proposed as a novel drug target in brain edema.These findings sug-gest that modulation of AQP4 expression or function may be beneficial in traumatic brain edema.

  18. Neuroimmunological Implications of AQP4 in Astrocytes.

    Science.gov (United States)

    Ikeshima-Kataoka, Hiroko

    2016-01-01

    The brain has high-order functions and is composed of several kinds of cells, such as neurons and glial cells. It is becoming clear that many kinds of neurodegenerative diseases are more-or-less influenced by astrocytes, which are a type of glial cell. Aquaporin-4 (AQP4), a membrane-bound protein that regulates water permeability is a member of the aquaporin family of water channel proteins that is expressed in the endfeet of astrocytes in the central nervous system (CNS). Recently, AQP4 has been shown to function, not only as a water channel protein, but also as an adhesion molecule that is involved in cell migration and neuroexcitation, synaptic plasticity, and learning/memory through mechanisms involved in long-term potentiation or long-term depression. The most extensively examined role of AQP4 is its ability to act as a neuroimmunological inducer. Previously, we showed that AQP4 plays an important role in neuroimmunological functions in injured mouse brain in concert with the proinflammatory inducer osteopontin (OPN). The aim of this review is to summarize the functional implication of AQP4, focusing especially on its neuroimmunological roles. This review is a good opportunity to compile recent knowledge and could contribute to the therapeutic treatment of autoimmune diseases through strategies targeting AQP4. Finally, the author would like to hypothesize on AQP4's role in interaction between reactive astrocytes and reactive microglial cells, which might occur in neurodegenerative diseases. Furthermore, a therapeutic strategy for AQP4-related neurodegenerative diseases is proposed. PMID:27517922

  19. Autoimmune AQP4 channelopathies and neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    Hinson, Shannon R; Lennon, Vanda A; Pittock, Sean J

    2016-01-01

    Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving group of central nervous system (CNS)-inflammatory autoimmune demyelinating diseases unified by a pathogenic autoantibody specific for the aquaporin-4 (AQP4) water channel. It was historically misdiagnosed as multiple sclerosis (MS), which lacks a distinguishing biomarker. The discovery of AQP4-IgG moved the focus of CNS demyelinating disease research from emphasis on the oligodendrocyte and myelin to the astrocyte. NMO is recognized today as a relapsing disease, extending beyond the optic nerves and spinal cord to include brain (especially in children) and skeletal muscle. Brain magnetic resonance imaging abnormalities, identifiable in 60% of patients at the second attack, are consistent with MS in 10% of cases. NMOSD-typical lesions (another 10%) occur in AQP4-enriched regions: circumventricular organs (causing intractable nausea and vomiting) and the diencephalon (causing sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Advances in understanding the immunobiology of AQP4 autoimmunity have necessitated continuing revision of NMOSD clinical diagnostic criteria. Assays that selectively detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 are promising prognostically. When referring to AQP4 autoimmunity, we suggest substituting the term "autoimmune aquaporin-4 channelopathy" for the term "NMO spectrum disorders." Randomized clinical trials are currently assessing the efficacy and safety of newer immunotherapies. Increasing therapeutic options based on understanding the molecular pathogenesis is anticipated to improve the outcome for patients with AQP4 channelopathy. PMID:27112688

  20. AQP4 plasma membrane trafficking or channel gating is not significantly modulated by phosphorylation at C-terminal serine residues

    DEFF Research Database (Denmark)

    Assentoft, Mette; Larsen, Brian R; Olesen, Emma T B;

    2014-01-01

    . Phosphorylation of aquaporins can regulate plasma membrane localization and, possibly, the unit water permeability via gating of the AQP channel itself. In vivo phosphorylation of six serine residues in the COOH terminus of AQP4 has been detected by mass spectrometry: Ser(276), Ser(285), Ser(315), Ser(316), Ser......Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain-blood interface. AQP4 serves as a water entry site during brain edema formation, and regulation of AQP4 may therefore be of therapeutic interest...... at the plasma membrane of transfected C6 cells being similar between the wild-type (WT) and mutant forms of AQP4. Activation of protein kinases A, C, and G in primary astrocytic cultures did not affect the plasma membrane abundance of AQP4. The unit water permeability was determined for the mutant AQP4s upon...

  1. Sensitivity of Aquaporin-4 Isoforms Binding to Antibody in Neuromyelitis Optica%表达AQP4不同亚型的细胞系检测AQP4抗体敏感性的研究

    Institute of Scientific and Technical Information of China (English)

    刘俊秀; 赖蓉; 钟德霞; 黄帆; 丰岩清; 梁秀龄

    2012-01-01

    [目的]研究表达不同亚型的AQP4细胞系检测中国人群视神经脊髓炎患者血清中AQP4抗体的敏感性.[方法]根据纳入标准共获取血清205例,其中包括视神经脊髓炎40例,长节段性脊髓炎39例,复发性视神经炎39例,多发性硬化47例,另设40例健康对照.使用稳定表达水通道蛋白4的四种细胞系HEK293/pcDNA3.1(+)-M23-AQP4、HEK293/pcDNA3.1(+)-M1-AQP4、HEK293/pEGFP-N3-M23-AQP4、HEK293/pEGFP-N3-M1-AQP4通过细胞间接免疫荧光法分别检测以上血清中的AQP4抗体.[结果]NMO-IgG普遍存在于视神经脊髓炎疾病谱中.AQP4抗体同AQP4两种亚型结合敏感性比较发现,M23-AQP4的敏感性高于M1-AQP4.同时绿色荧光蛋白作为标签蛋白,可能干扰抗体同AQP4的结合.[结论]M23-AQP4作为靶抗原检测血清中AQP4抗体优于M1-AQP4,临床中采用细胞间接免疫荧光法对抗体进行检测时应首选表达M23-AQP4亚型的细胞系进行检测.%[Objective] To investigate the performance of AQP4 isoform to detect AQP4 antibodies in neuromyelitis optica(NMO) patient's sera. [Methods] We tested 205 masked serum samples from 40 NMO patients, 39 longitudinally extensive transverse myelitis (LETM) patients, 39 patients with recurrent optic neuritis (rON), 47 patients with multiple sclerosis (MS) and 40 healthy controls with the indirect immunofluorescence with a composite substrate of HEK293/pcDNA3.1 (+ )-M23-AQP4, HEK293/ pcDNA3.1(+)-Ml-AQP4, HEK293/pEGFP-N3-M23-AQP4, HEK293/pEGFP-N3-Ml- AQP4. [Results] We found antibody to AQP4 was present in NMO spectrums. M23-AQP4 was more sensitivity than the M1-AQP4 and while the enhanced green fluorescent protein (EGFP) which was a tag protein may be interfere with the combination between the AQP4 antibody and AQP4. [Conclusion] M23-AQP4 appears to have a higher sensitivity than the M1-AQP4. It is expected to be a first consideration for the detection AQP4 antibody with the cell based assay.

  2. Expression of the Astrocyte Water Channel Aquaporin-4 in the Mouse Brain.

    Science.gov (United States)

    Hubbard, Jacqueline A; Hsu, Mike S; Seldin, Marcus M; Binder, Devin K

    2015-01-01

    Aquaporin-4 (AQP4) is a bidirectional water channel that is found on astrocytes throughout the central nervous system. Expression is particularly high around areas in contact with cerebrospinal fluid, suggesting that AQP4 plays a role in fluid exchange between the cerebrospinal fluid compartments and the brain. Despite its significant role in the brain, the overall spatial and region-specific distribution of AQP4 has yet to be fully characterized. In this study, we used Western blotting and immunohistochemical techniques to characterize AQP4 expression and localization throughout the mouse brain. We observed AQP4 expression throughout the forebrain, subcortical areas, and brainstem. AQP4 protein levels were highest in the cerebellum with lower expression in the cortex and hippocampus. We found that AQP4 immunoreactivity was profuse on glial cells bordering ventricles, blood vessels, and subarachnoid space. Throughout the brain, AQP4 was expressed on astrocytic end-feet surrounding blood vessels but was also heterogeneously expressed in brain tissue parenchyma and neuropil, often with striking laminar specificity. In the cerebellum, we showed that AQP4 colocalized with the proteoglycan brevican, which is synthesized by and expressed on cerebellar astrocytes. Despite the high abundance of AQP4 in the cerebellum, its functional significance has yet to be investigated. Given the known role of AQP4 in synaptic plasticity in the hippocampus, the widespread and region-specific expression pattern of AQP4 suggests involvement not only in fluid balance and ion homeostasis but also local synaptic plasticity and function in distinct brain circuits. PMID:26489685

  3. Brain expression of the water channels Aquaporin-1 and -4 in mice with acute liver injury, hyperammonemia and brain edema

    DEFF Research Database (Denmark)

    Eefsen, Martin; Jelnes, Peter; Schmidt, Lars E;

    2010-01-01

    Cerebral edema is a feared complication to acute liver failure (ALF), but the pathogenesis is still poorly understood. The water channels Aquaporin-1 (Aqp1) and -4 (Aqp4) has been associated with brain edema formation in several neuropathological conditions, indicating a possible role of Aqp1 and....../or Aqp4 in ALF mediated brain edema. We induced acute liver injury and hyperammonemia in mice, to evaluate brain edema formation and the parallel expression of Aqp1 and Aqp4 in ALF. Liver injury and hyperammonemia were induced by +D-galactosamine (GLN) plus lipopolysaccharide (LPS) intraperitoneally and......(6266) (p <0.05), and stationary levels for Aqp1. Aqp1 and Aqp4 mRNA were stationary. This study indicates that Aqp4, but not Aqp1, may be of importance in the pathogenesis of cortical brain edema in mice with ALF....

  4. Aquaporin-4–dependent K+ and water transport modeled in brain extracellular space following neuroexcitation

    OpenAIRE

    Jin, Byung-Ju; Zhang, Hua; Binder, Devin K.; Verkman, A.S.

    2013-01-01

    Potassium (K+) ions released into brain extracellular space (ECS) during neuroexcitation are efficiently taken up by astrocytes. Deletion of astrocyte water channel aquaporin-4 (AQP4) in mice alters neuroexcitation by reducing ECS [K+] accumulation and slowing K+ reuptake. These effects could involve AQP4-dependent: (a) K+ permeability, (b) resting ECS volume, (c) ECS contraction during K+ reuptake, and (d) diffusion-limited water/K+ transport coupling. To investigate the role of these mechan...

  5. Protection of Vascular Endothelial Growth Factor to Brain Edema Following Intracerebral Hemorrhage and Its Involved Mechanisms: Effect of Aquaporin-4.

    Directory of Open Access Journals (Sweden)

    Heling Chu

    Full Text Available Vascular endothelial growth factor (VEGF has protective effects on many neurological diseases. However, whether VEGF acts on brain edema following intracerebral hemorrhage (ICH is largely unknown. Our previous study has shown aquaporin-4 (AQP4 plays an important role in brain edema elimination following ICH. Meanwhile, there is close relationship between VEGF and AQP4. In this study, we aimed to test effects of VEGF on brain edema following ICH and examine whether they were AQP4 dependent. Recombinant human VEGF165 (rhVEGF165 was injected intracerebroventricularly 1 d after ICH induced by microinjecting autologous whole blood into striatum. We detected perihemotomal AQP4 protein expression, then examined the effects of rhVEGF165 on perihemotomal brain edema at 1 d, 3 d, and 7 d after injection in wild type (AQP4(+/+ and AQP4 knock-out (AQP4(-/- mice. Furthermore, we assessed the possible signal transduction pathways activated by VEGF to regulate AQP4 expression via astrocyte cultures. We found perihemotomal AQP4 protein expression was highly increased by rhVEGF165. RhVEGF165 alleviated perihemotomal brain edema in AQP4(+/+ mice at each time point, but had no effect on AQP4(-/- mice. Perihemotomal EB extravasation was increased by rhVEGF165 in AQP4(-/- mice, but not AQP4(+/+ mice. RhVEGF165 reduced neurological deficits and increased Nissl's staining cells surrounding hemotoma in both types of mice and these effects were related to AQP4. RhVEGF165 up-regulated phospharylation of C-Jun amino-terminal kinase (p-JNK and extracellular signal-regulated kinase (p-ERK and AQP4 protein in cultured astrocytes. The latter was inhibited by JNK and ERK inhibitors. In conclusion, VEGF reduces neurological deficits, brain edema, and neuronal death surrounding hemotoma but has no influence on BBB permeability. These effects are closely related to AQP4 up-regulation, possibly through activating JNK and ERK pathways. The current study may present new insights to

  6. Age-related changes in renal AQP3 and AQP4 expression in Sprague Dawley rats.

    Science.gov (United States)

    Jing, X H; Liu, J; Hou, W Y; Gao, Y

    2016-01-01

    Aquaporin (AQP) 3 and AQP4 are important in urine concentrating mechanisms and in other physiological functions such as brain water balance, cell migration, cell proliferation, fat metabolism, and epidermal hydration. The results of studies investigating AQP3 and AQP4 expression in the kidneys are inconsistent, and systematic research is rare. This study aimed to obtain a better understanding of the changes in renal AQP3 and AQP4 mRNA expression that take place with age. The expression of AQP3 and AQP4 mRNA, during prenatal and postnatal development, and during aging, was investigated in kidneys from Sprague-Dawley rats. The pattern of AQP3 expression was similar to that of AQP4 expression during development, and both were detected at gestational day 19 in the rat kidney where they maintained a stable level to postnatal day 14. Subsequently, a significant increase in expression was observed from day 21 to day 35, with peak expression occurring at day 35. No significant change in AQP3 or AQP4 mRNA expression was observed after day 35, apart from AQP4, which increased at day 540. Moreover, the expression of both AQP3 and AQP4 on day 850 was higher than on day -2, and lower than on days 28 and 35. The expression of AQP3 and AQP4 was similar on days 1, 7, 14, and 21. These findings indicate that mRNA expression of AQP3 and AQP4 varies with age, which should be considered when treating kidney disease in pediatric and elderly patients. PMID:27525904

  7. Effects of Different Doses of Levetiracetam on Aquaporin 4 Expression in Rats with Brain Edema Following Fluid Percussion Injury.

    Science.gov (United States)

    Jin, Hongbo; Li, Wenling; Dong, Changzheng; Ma, Li; Wu, Jiang; Zhao, Wenqing

    2016-01-01

    BACKGROUND This study was designed to investigate the effects of different doses of levetiracetam on aquaporin 4 (AQP4) expression in rats after fluid percussion injury. MATERIAL AND METHODS Sprague-Dawley rats were randomly divided into 4 groups: sham operation group, traumatic brain injury group, low-dose levetiracetam group, and high-dose levetiracetam group. Brain edema models were established by fluid percussion injury, and intervened by the administration of levetiracetam. Samples from the 4 groups were collected at 2, 6, 12, and 24 h, and at 3 and 7 days after injury. Histological observation was performed using hematoxylin-eosin staining and immunohistochemical staining. AQP4 and AQP4 mRNA expression was detected using Western blot assay and RT-PCR. Brain water content was measured by the dry-wet method. RESULTS Compared with the traumatic brain injury group, brain water content, AQP4 expression, and AQP4 mRNA expression were lower in the levetiracetam groups at each time point and the differences were statistically significant (Ppercussion injury by down-regulating AQP4 and AQP4 mRNA expression. There is a dose-effect relationship in the preventive effect of levetiracetam within a certain extent. PMID:26927633

  8. Sex- and region-specific alterations of basal amino acid and monoamine metabolism in the brain of aquaporin-4 knockout mice.

    Science.gov (United States)

    Fan, Yi; Zhang, Jing; Sun, Xiu-Lan; Gao, Lin; Zeng, Xiao-Ning; Ding, Jian-Hua; Cao, Cong; Niu, Ling; Hu, Gang

    2005-11-15

    Aquaporin-4 (AQP4), a predominant water channel of the brain, mediates transmembrane water movement at the blood-brain barrier and brain-cerebrospinal fluid interface. A broad pattern of evidence indicates that AQP4 and regulators of its expression are potential targets for treatment of brain swelling, but whether it participates in the regulation of neurotransmission has not been reported. We examined neurochemical differences between AQP4-knockout and wild-type mice with particular focus on neurotransmission. Basal tissue neurotransmitter and metabolite levels were measured by high-performance liquid chromatography. Significant sex- and region-specific differences of amino acids and monoamines were found in the brain of wild-type and AQP4-knockout mice. In cortex, striatum, and hippocampus of male AQP4-knockout mice, an increase of glutamine and decrease of aspartate were observed. Glutamate was increased only in female AQP4-knockout mice. The lack of AQP4 failed to affect the levels of gamma-aminobutyric acid and taurine. In the medial prefrontal cortex of AQP4-knockout mice, the levels of serotonin and norepinephrine were increased, but no significant change in dopamine level was found. In the striatum of male AQP4-knockout mice, the levels of dopamine and serotonin were remarkably increased, which was not found in female mice. In the hypothalamus of AQP4-knockout mice, only the serotonin level was altered. These results provide the first evidence that the lack of AQP4 expression is accompanied by sex- and region-specific alterations in brain amino acid and monoamine metabolism. PMID:16237719

  9. Immunocytochemical Studies of Aquaporin 4, Kir4.1, and α1-syntrophin in the Astrocyte Endfeet of Mouse Brain Capillaries

    International Nuclear Information System (INIS)

    One of the most important physiological roles of brain astrocytes is the maintenance of extracellular K+ concentration by adjusting the K+ influx and K+ efflux. The inwardly rectifying K+ channel Kir4.1 has been identified as an important member of K+ channels and is highly concentrated in glial endfeet membranes. Aquaporin (AQP) 4 is another abundantly expressed molecule in astrocyte endfeet membranes. We examined the ultrastructural localization of Kir4.1, AQP4, α1-syntrophin, and β-spectrin molecules to understand the functional role(s) of Kir4.1 and AQP4. Immunogold electron microscopy of these molecules showed that the signals of these molecules were present along the plasma membranes of astrocyte endfeet. Double immunogold electron microscopy showed frequent co-localization in the combination of molecules of Kir4.1 and AQP4, Kir4.1 and α1-syntrophin, and AQP4 and α1-syntrophin, but not those of AQP4 and β-spectrin. Our results support biochemical evidence that both Kir4.1 and AQP4 are associated with α1-syntrophin by way of postsynaptic density-95, Drosophila disc large protein, and the Zona occludens protein I protein-interaction domain. Co-localization of AQP4 and Kir4.1 may indicate that water flux mediated by AQP4 is associated with K+ siphoning

  10. Phosphorylation of rat aquaporin-4 at Ser(111) is not required for channel gating

    DEFF Research Database (Denmark)

    Assentoft, Mette; Kaptan, Shreyas; Fenton, Robert A;

    2013-01-01

    is therefore of therapeutic interest. Phosphorylation of some aquaporins has been proposed to regulate their water permeability via gating of the channel itself. Protein kinase (PK)-dependent phosphorylation of Ser(111) has been reported to increase the water permeability of AQP4 expressed in an astrocytic......Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain-blood interface. AQP4 has been described as an important entry and exit site for water during formation of brain edema and regulation of AQP4...... cell line. This possibility was, however, questioned based on the crystal structure of the human AQP4. Our study aimed to resolve if Ser(111) was indeed a site involved in phosphorylation-mediated gating of AQP4. The water permeability of AQP4-expressing Xenopus oocytes was not altered by a range...

  11. Trafficking and phosphorylation dynamics of AQP4 in histamine-treated human gastric cells.

    NARCIS (Netherlands)

    Carmosino, M.; Procino, G.; Tamma, G.; Mannucci, R.; Svelto, M.; Valenti, G.

    2007-01-01

    BACKGROUND INFORMATION: AQP4 (aquaporin 4) internalization and a concomitant decrease in the osmotic water permeability coefficient (Pf) after histamine exposure has been reported in AQP4-transfected gastric HGT1 cells. RESULTS: In the present study we report that AQP4 internalization is followed by

  12. Effects of dexamthasone with different doses on aquaporin-4 in brain of intracerebral hemorrhage rats

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective:To determine the relationship between the expression of aquaporin-4(AQP4) after intracerebral hemorrhage and dexamethasone treated. Methods:Collagenase Ⅶ was injected in caudate nucleus in a stereotaxis frame to establish the intracerebral hemorrhage(ICH) animal models. The intracerebral hemorrhage(ICH) rats were randomly divided into four groups: the sham group (group A), the ICH group(group B), low dosertreated group(group C), moderate dose group(group D) and high dose group(group E). The groups were respectively received an intraperitoneal dexamethasone injection with 1 mg/kg, 15 mg/kg, 30 mg/kg, twice a day for three days. The brain water content(BWC), the permeability of blood-brain barrier(BBB) and the expression of AQP4 were observed. Results:Both the BBB disruption and AQP4 expression decreased in treated groups, and the AQP4 expression had a dose-dependent manner in the dexamethasone treatment. And it seemed that low dose dexamethasone was in favor of brain swelling elimination, but the higher dosage had not similar effect. Conclusion:Dexamethesone may play a critical role on expression of AQP4 in the physiopathology of hemorrhagic edema.

  13. Metal ion toxins and brain aquaporin-4 expression: an overview

    Directory of Open Access Journals (Sweden)

    Adriana eXimenes-Da-Silva

    2016-06-01

    Full Text Available Metal ions such as iron, zinc, and manganese are essential to metabolic functions, protein synthesis, neurotransmission, and antioxidant neuroprotective mechanisms. Conversely, non-essential metals such as mercury and lead are sources of human intoxication due to occupational activities or environmental contamination. Essential or non-essential metal accumulation in the central nervous system (CNS results in changes in blood-brain barrier (BBB permeability, as well as triggering microglia activation and astrocyte reactivity and changing water transport through the cells, which could result in brain swelling. Aquaporin-4 is the main water channel in the CNS, is expressed in astrocyte foot processes in brain capillaries and along the circumventricular epithelium in the ventricles, and has important physiological functions in maintaining brain osmotic homeostasis and supporting brain excitability through regulation of the extracellular space. Some evidence has pointed to a role of AQP4 during metal intoxication in the brain, where it may act in a dual form as a neuroprotector or a mediator of the development of oxidative stress in neurons and astrocytes, resulting in brain swelling and neuronal damage. This mini-review presents the way some metal ions affect changes in AQP4 expression in the CNS and discuss the ways in which water transport in brain cells can be involved in brain damage.

  14. Metal Ion Toxins and Brain Aquaporin-4 Expression: An Overview.

    Science.gov (United States)

    Ximenes-da-Silva, Adriana

    2016-01-01

    Metal ions such as iron, zinc, and manganese are essential to metabolic functions, protein synthesis, neurotransmission, and antioxidant neuroprotective mechanisms. Conversely, non-essential metals such as mercury and lead are sources of human intoxication due to occupational activities or environmental contamination. Essential or non-essential metal accumulation in the central nervous system (CNS) results in changes in blood-brain barrier (BBB) permeability, as well as triggering microglia activation and astrocyte reactivity and changing water transport through the cells, which could result in brain swelling. Aquaporin-4 is the main water channel in the CNS, is expressed in astrocyte foot processes in brain capillaries and along the circumventricular epithelium in the ventricles, and has important physiological functions in maintaining brain osmotic homeostasis and supporting brain excitability through regulation of the extracellular space. Some evidence has pointed to a role of AQP4 during metal intoxication in the brain, where it may act in a dual form as a neuroprotector or a mediator of the development of oxidative stress in neurons and astrocytes, resulting in brain swelling and neuronal damage. This mini-review presents the way some metal ions affect changes in AQP4 expression in the CNS and discuss the ways in which water transport in brain cells can be involved in brain damage. PMID:27313504

  15. Aquaporin-4 deficiency attenuates acute lesions but aggravates delayed lesions and microgliosis after cryoinjury to mouse brain

    Institute of Scientific and Technical Information of China (English)

    Wen-Zhen Shi; Chun-Zhen Zhao; Bing Zhao; Xiao-Liang Zheng; San-Hua Fang; Yun-Bi Lu; Wei-Ping Zhang; Zhong Chen; Er-Qing Wei

    2012-01-01

    Objective To determine whether aquaporin-4 (AQP4) regulates acute lesions,delayed lesions,and the associated microglial activation after cryoinjury to the brain.Methods Brain cryoinjury was applied to AQP4 knockout (KO)and wild-type mice.At 24 h and on days 7 and 14 after cryoinjury,lesion volume,neuronal loss,and densities of microglia and astrocytes were determined,and their changes were compared between AQP4 KO and wild-type mice.Results Lesion volume and neuronal loss in AQP4 KO mice were milder at 24 h following cryoinjury,but worsened on days 7 and 14,compared to those in wild-type mice.Besides,microglial density increased more,and astrocyte proliferation and glial scar formation were attenuated on days 7 and 14 in AQP4 KO mice.Conclusion AQP4 deficiency ameliorates acute lesions,but worsens delayed lesions,perhaps due to the microgliosis in the late phase.

  16. Comparative Analysis of Methods for Titrating Anti-aquaporin-4 Antibodies in Neuromyelitis Optica Spectrum%不同方法检测NMO-IgG/抗AQP4抗体滴度的比较

    Institute of Scientific and Technical Information of China (English)

    赖蓉; 刘俊秀; 孙巧松; 黄帆; 丰岩清

    2012-01-01

    [目的]旨在比较鼠脑法和细胞法检测中国人视神经脊髓炎(NMO)疾病谱(NMOSD)的滴度是否具有一致性.[方法]每个样本分别采用鼠脑法和细胞法检测,阳性血清采取倍比稀释以确定最终稀释倍数.应用盲法检测血清NMO-IgG/抗水通道蛋白4(AQP4)110例,其中视神经脊髓炎19例,复发性视神经炎(RON)17例,纵形扩展性脊髓炎(LETM)13例,多发性硬化(MS)31例,健康对照(HC)30例;对其检测的阳性率和滴度进行分析,并比较滴度与脊髓病变长度的相关性.[结果]大部分样本用两种方法检测的滴度之间都缺乏一致性.NMO组患者NMO-IgG/抗AQP4抗体鼠脑法(63.2%,12/19),细胞法(89.5%,17/19),RON组鼠脑法(47.1%,8/17),细胞法(70.6%,12/17),LETM组鼠脑法(46.2%,6/13),细胞法(69.2%,9/13),MS组鼠脑法(6.5%,2/31),细胞法(9.7%,3/31).鼠脑法和细胞法检测所得到的NMOSD患者NMO-IgG/AQP4抗体滴度均和脊髓病变的长度无线性相关性,两种检测方法之间也缺乏滴度线性相关性.[结论]鼠脑法和细胞法检测抗体滴度的不一致性提示有必要进行多因素相关性研究以探讨影响两种检测方法抗体滴度的因素.%[Objective] This study was aimed to investigate the titer consistency in parallel between tissue-based UFA and cell-based UFA in Chinese patients with neuromyelitis optica (NMO) spectrum disorders. [Methods] Every sample was tested by the tissue-based IIFA and cell-based UFA separately. Positive serum samples were titrated in doubling dilutions,to ascertain the maximum dilution that yielded positive results separately. We assessed the seroprevalence and the titer consistency of anti-aquaporin-4 antibodies of serum samples from patients with neuromyelitis optica (NMO, 19), recurrent optic neuritis (RON, 17), longitudinally extensive transverse myelitis (LETM, 13), multiple sclerosis (MS,31), health control (HC, 30). Moreover, we analyzed the relation of anti-aquaporin-4 antibody

  17. POST-GOLGI SUPRAMOLECULAR ASSEMBLY OF AQUAPORIN-4 IN ORTHOGONAL ARRAYS

    Science.gov (United States)

    Rossi, Andrea; Baumgart, Florian; van Hoek, Alfred N.; Verkman, Alan S.

    2012-01-01

    The supramolecular assembly of aquaporin-4 (AQP4) in orthogonal arrays of particles (OAPs) involves N-terminus interactions of the M23-AQP4 isoform. We found AQP4 OAPs in cell plasma membranes but not in endoplasmic reticulum (ER) or Golgi, as shown by: (i) native gel electrophoresis of brain and AQP4-transfected cells; (ii) photobleaching recovery of GFP-AQP4 chimeras in live cells; and (iii) freeze-fracture electron microscopy (FFEM). We found that AQP4 OAP formation in plasma membranes but not Golgi was not related to AQP4 density, pH, membrane lipid composition, C-terminal PDZ-domain interactions or α-syntrophin expression. Remarkably, however, fusion of AQP4-containing Golgi vesicles with (AQP4-free) plasma membrane vesicles produced OAPs, suggesting the involvement of plasma membrane factor(s) in AQP4 OAP formation. In investigating additional possible determinants of OAP assembly we discovered membrane curvature-dependent OAP assembly, in which OAPs were disrupted by extrusion of plasma membrane vesicles to ~110 nm diameter, but not to ~220 nm diameter. We conclude that AQP4 supramolecular assembly in OAPs is a post-Golgi phenomenon involving plasma membrane-specific factor(s). Post-Golgi and membrane curvature-dependent OAP assembly may be important for vesicle transport of AQP4 in the secretory pathway and AQP4-facilitated astrocyte migration, and suggests a novel therapeutic approach for neuromyelitis optica (NMO). PMID:21981006

  18. H95 Is a pH-Dependent Gate in Aquaporin 4

    DEFF Research Database (Denmark)

    Kaptan, Shreyas; Assentoft, Mette; Schneider, Hans Peter;

    2015-01-01

    Aquaporin 4 (AQP4) is a transmembrane protein from the aquaporin family and is the predominant water channel in the mammalian brain. The regulation of permeability of this protein could be of potential therapeutic use to treat various forms of damage to the nervous tissue. In this work, based...... on data obtained from in silico and in vitro studies, a pH sensitivity that regulates the osmotic water permeability of AQP4 is demonstrated. The results indicate that AQP4 has increased water permeability at conditions of low pH in atomistic computer simulations and experiments carried out on Xenopus...... oocytes expressing AQP4. With molecular dynamics simulations, this effect was traced to a histidine residue (H95) located in the cytoplasmic lumen of AQP4. A mutant form of AQP4, in which H95 was replaced with an alanine (H95A), loses sensitivity to cytoplasmic pH changes in in vitro osmotic water...

  19. Aquaporin-4: orthogonal array assembly, CNS functions, and role in neuromyelitis optica

    Institute of Scientific and Technical Information of China (English)

    Alan S VERKMAN; Julien RATELADE; Andrea ROSSI; Hua ZHANG; Lukmanee TRADTRANTIP

    2011-01-01

    Aquaporin-4 (AQP4) is a water-selective transporter expressed in astrocytes throughout the central nervous system, as well as in kidney, lung, stomach and skeletal muscle. The two AQP4 isoforms produced by alternative spicing, M1 and M23 AQP4, form heterotetramers that assemble in cell plasma membranes in supramolecular structures called orthogonal arrays of particles (OAPs).Phenotype analysis of AQP4-null mice indicates the involvement of AQP4 in brain and spinal cord water balance, astrocyte migration, neural signal transduction and neuroinflammation. AQP4-null mice manifest reduced brain swelling in cytotoxic cerebral edema, but increased brain swelling in vasogenic edema and hydrocephalus. AQP4 deficiency also increases seizure duration,impairs glial scarring, and reduces the severity of autoimmune neuroinflammation. Each of these phenotypes is likely explicable on the basis of reduced astrocyte water permeability in AQP4 deficiency. AQP4 is also involved in the neuroinflammatory demyelinating disease neuromyelitis optica (NMO), where autoantibodies (NMO-lgG) targeting AQP4 produce astrocyte damage and inflammation.Mice administered NMO-lgG and human complement by intracerebral injection develop characteristic NMO lesions with neuroinflammation, demyelination, perivascular complement deposition and loss of glial fibrillary acidic protein and AQP4 immunoreactivity.Our findings suggest the potential utility of AQP4-based therapeutics, including small-molecule modulators of AQP4 water transport function for therapy of brain swelling, injury and epilepsy, as well as small-molecule or monoclonal antibody blockers of NMO-lgG binding to AQP4 for therapy of NMO.

  20. Cerebrospinal fluid antibodies to aquaporin-4 in neuromyelitis optica and related disorders: frequency, origin, and diagnostic relevance

    Directory of Open Access Journals (Sweden)

    Jarius Sven

    2010-09-01

    Full Text Available Abstract Background In 70-80% of cases, neuromyelitis optica (NMO is associated with highly specific serum auto-antibodies to aquaporin-4 (termed AQP4-Ab or NMO-IgG. Recent evidence strongly suggests that AQP4-Ab are directly involved in the immunopathogenesis of NMO. Objective To assess the frequency, syndrome specificity, diagnostic relevance, and origin of cerebrospinal fluid (CSF AQP4-Ab in patients with NMO spectrum disorders (NMOSD. Methods 87 CSF samples from 37 patients with NMOSD and 42 controls with other neurological diseases were tested for AQP4-Ab in a cell based assay using recombinant human AQP4. Twenty-three paired CSF and serum samples from AQP4-Ab seropositive NMOSD patients were further analysed for intrathecal IgG synthesis to AQP4. Results AQP4-Ab were detectable in 68% of CSF samples from AQP4-Ab seropositive patients with NMOSD, but in none of the CSF samples from AQP4-Ab seronegative patients with NMOSD and in none of the control samples. Acute disease relapse within 30 days prior to lumbar puncture, AQP4-Ab serum titres >1:250, and blood-CSF barrier dysfunction, but not treatment status, predicted CSF AQP4-Ab positivity. A positive AQP4-specific antibody index was present in 1/23 samples analysed. Conclusions AQP4-Ab are detectable in the CSF of most patients with NMOSD, mainly during relapse, and are highly specific for this condition. In the cohort analysed in this study, testing for CSF AQP4-Ab did not improve the sensitivity and specificity of the current diagnostic criteria for NMO. The substantial lack of intrathecal AQP4-Ab synthesis in patients with NMOSD may reflect the unique localisation of the target antigen at the blood brain barrier, and is important for our understanding of the immunopathogenesis of the disease.

  1. 牛磺酸对重度颅脑创伤大鼠脑组织AQP4/牛磺酸转运体基因的影响%Effect of Taurine on AQP4/Taurine transporter gene in rats with traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    李晓茜; 黄慧玲; 范维嘉; 蔡英; 武俏丽

    2011-01-01

    目的 研究牛磺酸(Tau)对重度颅脑创伤(TBI)大鼠脑组织的脑组织含水量、水通道蛋白-4(AQP-4)/Tau转运体(TAUT)基因表达的影响.方法 按随机数字表法将84只雄性SD大鼠分为7组:假手术组(Sham组)、脑外伤组(TBI组)、Tau治疗组(Tau组),Tau预防组(Pre-Tau组)、β-丙氨酸组(β-Ala组)、维生素C组(Vc组)、叶酸组(Fa组),每组12只.后6组均采用液压打击制作重度TBI模型.造模成功后即刻尾静脉给药200 mg/kg.Sham组和TBI组给予相同量等渗盐水,24 h后取脑.采用HE染色法观察TBI后各组脑组织形态学变化、测定脑组织含水量,用荧光定量RT-PCR方法检测AQP-4/TAUT基因表达.结果 形态学检查:TBI 24 h后,神经细胞肿胀,细胞丢失,细胞核固缩,突起短小消失,坏死灶边缘可见炎性细胞浸润,β-Ala组同TBI组.但与TBI组比较,Tau组、Vc组、Fa组、Pre-Tau组形态上无显著改善;脑组织含水量:与Sham组相比,TBI组、β-Ala组伤后24 h显著升高(P<0.05).而Tau组、Vc组、Fa组明显降低,与Sham组无统计学差异;Pre-Tau组显著低于Sham组(P<0.05).基因表达:与Sham组相比,TBI组脑组织AQP-4 mRNA表达量显著升高(P<0.05),Fa组TAUT mRNA表达量显著升高(P<0.05).结论 Tau、Vc、Fa及Tau预防性治疗均可以显著降低脑水肿和AQP-4基因表达,对TBI后脑水肿有较好的治疗作用,但Tau、Vc对TBI早期的TAUT无调节作用,其对脑组织含水量的有效性并不是通过调节TAUT实现的.%Objective To investigate the changes of the brain water content and AQP4/taurine transporter gene expression in brain tissue after taurine treatment in rats with traumatic brain injury (TBI). Methods A total of 84 male SD rats were randomly divided into 7 groups: Sham group, traumatic brain injury TBI group, Tau group, Pre-Tau group, β-Ala group, Vc group, Fa group. TBI models of the latter six groups were performed by lateral fluid percussion. The rats were administered drugs ( drug dose

  2. AQP4-dependent water transport plays a functional role in exercise-induced skeletal muscle adaptations.

    Science.gov (United States)

    Basco, Davide; Blaauw, Bert; Pisani, Francesco; Sparaneo, Angelo; Nicchia, Grazia Paola; Mola, Maria Grazia; Reggiani, Carlo; Svelto, Maria; Frigeri, Antonio

    2013-01-01

    In this study we assess the functional role of Aquaporin-4 (AQP4) in the skeletal muscle by analyzing whether physical activity modulates AQP4 expression and whether the absence of AQP4 has an effect on osmotic behavior, muscle contractile properties, and physical activity. To this purpose, rats and mice were trained on the treadmill for 10 (D10) and 30 (D30) days and tested with exercise to exhaustion, and muscles were used for immunoblotting, RT-PCR, and fiber-type distribution analysis. Taking advantage of the AQP4 KO murine model, functional analysis of AQP4 was performed on dissected muscle fibers and sarcolemma vesicles. Moreover, WT and AQP4 KO mice were subjected to both voluntary and forced activity. Rat fast-twitch muscles showed a twofold increase in AQP4 protein in D10 and D30 rats compared to sedentary rats. Such increase positively correlated with the animal performance, since highest level of AQP4 protein was found in high runner rats. Interestingly, no shift in muscle fiber composition nor an increase in AQP4-positive fibers was found. Furthermore, no changes in AQP4 mRNA after exercise were detected, suggesting that post-translational events are likely to be responsible for AQP4 modulation. Experiments performed on AQP4 KO mice revealed a strong impairment in osmotic responses as well as in forced and voluntary activities compared to WT mice, even though force development amplitude and contractile properties were unvaried. Our findings definitively demonstrate the physiological role of AQP4 in supporting muscle contractile activity and metabolic changes that occur in fast-twitch skeletal muscle during prolonged exercise. PMID:23520529

  3. AQP4-dependent water transport plays a functional role in exercise-induced skeletal muscle adaptations.

    Directory of Open Access Journals (Sweden)

    Davide Basco

    Full Text Available In this study we assess the functional role of Aquaporin-4 (AQP4 in the skeletal muscle by analyzing whether physical activity modulates AQP4 expression and whether the absence of AQP4 has an effect on osmotic behavior, muscle contractile properties, and physical activity. To this purpose, rats and mice were trained on the treadmill for 10 (D10 and 30 (D30 days and tested with exercise to exhaustion, and muscles were used for immunoblotting, RT-PCR, and fiber-type distribution analysis. Taking advantage of the AQP4 KO murine model, functional analysis of AQP4 was performed on dissected muscle fibers and sarcolemma vesicles. Moreover, WT and AQP4 KO mice were subjected to both voluntary and forced activity. Rat fast-twitch muscles showed a twofold increase in AQP4 protein in D10 and D30 rats compared to sedentary rats. Such increase positively correlated with the animal performance, since highest level of AQP4 protein was found in high runner rats. Interestingly, no shift in muscle fiber composition nor an increase in AQP4-positive fibers was found. Furthermore, no changes in AQP4 mRNA after exercise were detected, suggesting that post-translational events are likely to be responsible for AQP4 modulation. Experiments performed on AQP4 KO mice revealed a strong impairment in osmotic responses as well as in forced and voluntary activities compared to WT mice, even though force development amplitude and contractile properties were unvaried. Our findings definitively demonstrate the physiological role of AQP4 in supporting muscle contractile activity and metabolic changes that occur in fast-twitch skeletal muscle during prolonged exercise.

  4. Study on the effects of thrombin on AQP4 mRNA and AQP4 protein expression in rat primary astrocytes

    Institute of Scientific and Technical Information of China (English)

    Jinghua Zhou; Xuebing Cao; Shenggang Sun

    2006-01-01

    Objective: To study the biologic effects of various concentrations of thrombin on aquaporin 4 (AQP4) expression in rat primary cultured astrocytes, and to explore the regulation mechanism of transmembrane water transportation in astrocytes after intracerebral hemorrhage (ICH). Methods: Primary cultured astrocytes were incubated in culture mediums containing various concentrations of thrombin for 24 h and harvested. AQP4 mRNA and AQP4 protein expression were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical technique. Cell apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) technique. Cell morphology was observed by phase contrast microscope, and cell viability was assayed by MTT. Results: AQP4 mRNA and AQP4 protein showed a low expression in normal astrocytes. The expression of AQP4 mRNA and AQP4 protein significantly increased in the astrocytes treated with 100 U/ml or 200 U/ml thrombin (P < 0.01),and these astrocytes swelled. The number of TUNEL positive cells significantly increased. On the other hand, AQP4 mRNA and AQP4 protein expression were down-regulated in the astrocytes treated with 0.5 U/ml or l U/ml thrombin (P < 0.05),and the cell morphology did not change. Few TUNEL positive cells were observed. Conclusion: AQP4 over-expression induced by high concentrations of thrombin causes an increased permeability of water in astrocytic membrane. On the contrary, the decreased AQP4 expression prevents the astrocytes from swelling and apoptosis.

  5. Reperfusion of the rat brain tissues following acute ischemia: the correlation among diffusion-weighted imaging, histopathology,and aquaporin-4 expression

    Institute of Scientific and Technical Information of China (English)

    LU Hong; HU Hui; HE Zhan-ping

    2011-01-01

    Background Although some studies have reported that aquaporin-4 (AQP4) plays a role in the post-ischemic edema formation and diffusion-weighted imaging (DWI), little is known about the AQP4 expression in stage of the reperfusion following acute cerebral ischemia, as well as the correlation between histopathology and DWl. The aim of the study was to investigate the correlation among DWl, histopathology and the AQP4 expression in the reperfused rat brain tissues following acute ischemia.Methods Seventy Wistar rats were randomly divided into a control group (group A), and several occluded and reperfusion groups. They had their middle cerebral artery unilaterally occluded (MCAO) for 30 minutes (group B) followed by 30 minutes (group D) or 60 minutes (group E) of reperfusion, or 60 minutes of MCAO (group C) followed by 30 minutes (group F), or 60 minutes (group G) of reperfusion (n=10 for each group). All rats underwent DWl scanning.The relative apparent diffusion coefficient (rADC) value of each rat was calculated. All the rats were sacrificed and the cerebral ischemic tissues were examined for histopathology. Real-time fluro-quantitative polymerase chain reaction (RT-PCR) and Western-blotting were performed. The amount of AQP4 mRNA (Ex △△Ct) and AQP4 protein (Q) was statistically analyzed. The correlation between rADC values and AQP4 mRNA expression was analyzed with the Pearson correlation test.Results In all the reperfusion groups, the areas of hyper-intensity signal in DWl were decreased, and the rADC value increased and the AQP4 expression decreased significantly compared with the occluded group (t=26.89, t=18.26, P<0.01). There was a negative correlation between AQP4 mRNA expression and rADC values (r=-0.72, P<0.01). A mixed edema, composed of cerebral intracelluar edema and vasogenic brain edema, was observed in all the reperfusion groups.It was more prevalent in groups D and F than in the groups E and G. With the reperfusion time postponed, the cerebral

  6. AQP4-Dependent Water Transport Plays a Functional Role in Exercise-Induced Skeletal Muscle Adaptations

    OpenAIRE

    Davide Basco; Bert Blaauw; Francesco Pisani; Angelo Sparaneo; Grazia Paola Nicchia; Maria Grazia Mola; Carlo Reggiani; Maria Svelto; Antonio Frigeri

    2013-01-01

    In this study we assess the functional role of Aquaporin-4 (AQP4) in the skeletal muscle by analyzing whether physical activity modulates AQP4 expression and whether the absence of AQP4 has an effect on osmotic behavior, muscle contractile properties, and physical activity. To this purpose, rats and mice were trained on the treadmill for 10 (D10) and 30 (D30) days and tested with exercise to exhaustion, and muscles were used for immunoblotting, RT-PCR, and fiber-type distribution analysis. Ta...

  7. Neuromyelitis optica pathogenesis and aquaporin 4

    Directory of Open Access Journals (Sweden)

    Kerr Douglas

    2008-05-01

    Full Text Available Abstract Neuromyelitis optica (NMO is a severe, debilitating human disease that predominantly features immunopathology in the optic nerves and the spinal cord. An IgG1 autoantibody (NMO-IgG that binds aquaporin 4 (AQP4 has been identified in the sera of a significant number of NMO patients, as well as in patients with two related neurologic conditions, bilateral optic neuritis (ON, and longitudinal extensive transverse myelitis (LETM, that are generally considered to lie within the NMO spectrum of diseases. NMO-IgG is not the only autoantibody found in NMO patient sera, but the correlation of pathology in central nervous system (CNS with tissues that normally express high levels of AQP4 suggests NMO-IgG might be pathogenic. If this is the case, it is important to identify and understand the mechanism(s whereby an immune response is induced against AQP4. This review focuses on open questions about the "events" that need to be understood to determine if AQP4 and NMO-IgG are involved in the pathogenesis of NMO. These questions include: 1 How might AQP4-specific T and B cells be primed by either CNS AQP4 or peripheral pools of AQP4? 2 Do the different AQP4-expressing tissues and perhaps the membrane structural organization of AQP4 influence NMO-IgG binding efficacy and thus pathogenesis? 3 Does prior infection, genetic predisposition, or underlying immune dysregulation contribute to a confluence of events which lead to NMO in select individuals? A small animal model of NMO is essential to demonstrate whether AQP4 is indeed the incipient autoantigen capable of inducing NMO-IgG formation and NMO. If the NMO model is consistent with the human disease, it can be used to examine how changes in AQP4 expression and blood-brain barrier (BBB integrity, both of which can be regulated by CNS inflammation, contribute to inductive events for anti-AQP4-specific immune response. In this review, we identify reagents and experimental questions that need to be

  8. Water Permeability Through Aquaporin-4 is regulated by Protein Kinase C and becomes Rate-Limiting for Glioma Invasion

    OpenAIRE

    McCoy, Eric S; Haas, Brian R.; Sontheimer, Harald

    2009-01-01

    Glial derived tumors, gliomas, are highly invasive cancers that invade normal brain through the extracellular space. To navigate the tortuous extracellular spaces cells undergo dynamic changes in cell volume, which entails water flux across the membrane through aquaporins (AQPs). Two members of this family, AQP1 and AQP4 are highly expressed in primary brain tumor biopsies and both have a consensus phosphorylation site for PKC, which is a known regulator of glioma cell invasion. AQP4 colocali...

  9. Fluoxetine Requires the Endfeet Protein Aquaporin-4 to Enhance Plasticity of Astrocyte Processes

    OpenAIRE

    Di Benedetto, Barbara; Malik, Victoria A.; Begum, Salina; Jablonowski, Lena; Gómez-González, Gabriela B.; Inga D. Neumann; Rupprecht, Rainer

    2016-01-01

    Morphological alterations in astrocytes are characteristic for post mortem brains of patients affected by major depressive disorder (MDD). Recently, a significant reduction in the coverage of blood vessels (BVs) by aquaporin-4 (AQP-4)-positive astrocyte endfeet has been shown in the prefrontal cortex (PFC) of MDD patients, suggesting that either alterations in the morphology of endfeet or in AQP-4 distribution might be responsible for the disease phenotype or constitute a consequence of its p...

  10. Fluoxetine requires the endfeet protein aquaporin-4 to enhance plasticity of astrocyte processes

    OpenAIRE

    Inga D. Neumann; Di Benedetto, Barbara; Malik, Victoria A.; Begum, Salina; Jablonowski, Lena; Gómez-González, Gabriela B.; Rupprecht, Rainer

    2016-01-01

    Morphological alterations in astrocytes are characteristic for post mortem brains of patients affected by major depressive disorder (MDD). Recently, a significant reduction in the coverage of blood vessels (BVs) by aquaporin-4 (AQP-4)-positive astrocyte endfeet has been shown in the prefrontal cortex (PFC) of MDD patients, suggesting that either alterations in the morphology of endfeet or in AQP-4 distribution might be responsible for the disease phenotype or constitute a consequence of its p...

  11. Expression of AQP4 and susceptivity to high-altitude cerebral edema in bovine brain%黄牛脑水通道蛋白4的表达及其对高原脑水肿的易感性

    Institute of Scientific and Technical Information of China (English)

    宋国强; 王建林; 徐元青; 伍国芬; 邵宝平

    2011-01-01

    为了探讨黄牛对高原脑水肿的易感性,并为青藏高原养牛业提供参考,运用免疫组织化学SABC染色法并采用Image-Pro Plus 6.0软件,对成年黄牛大脑不同功能区水通道蛋白4(AQP4)的表达及分布特征进行了研究.结果显示,黄牛不同功能区脑组织中AQP4表达面积(S)和积分光密度(IOD)值的大小顺序为S扣带回>S中央前回>S丘脑>S尾状核,IOD扣带回>IOD中央前回>IOD丘脑>IOD尾状核,且扣带回和中央前回的S和IOD值均显著高于丘脑和尾状核(P<0.01).结果证实,成年黄牛脑不同功能区、同功能区不同层及同功能区同层不同类型细胞对水的通透性及代谢功能存在较大差异,对脑水肿的易感性是不同的.%To investigate the susceptivity of cattle to the high altitude cerebral edema as well as provide reference and theory evidence to the cattle-raising industry in Qinghai-Tibet Plateau, the expression and distributional characteristics of adult cattle cerebral aquaporin 4 (AQP4) in different functional area were studied by using immunohistochemical SABC and Image-Pro Plus 6.0 software. Statistical analysis showed that both the immunostaining area(S) and the integral optical density(IOD) value of the cingulated gyrus and precentral gyrus were significantly larger than thalamus and caudate nucleus(P<0. 01, Scingulated gyrus>Sprecentral gyrus > Sthalamus > Scaudate uncleus and IODcingulated gyrus > IODprecentral gyrus > IODthalamus > IODcaudate nucleus ). The results showed that there was comparatively large discrepancy of cell water permeability and metabolism function among different functional area in cattle brain, distinct peers of a functional area and distinguished type cells in the same functional area and peer which might have different susceptivity to cerebral edema.

  12. Effect of ketamine on aquaporin-4 expression and neuronal apoptosis in brain tissues following brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Zangong Zhou; Xiangyu Ji; Li Song; Jianfang Song; Shiduan Wang; Yanwei Yin

    2006-01-01

    BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats.OBJECTIVE: To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury.DESIGN: Randomized grouping design, controlled animal trial.SETTING: Department of Anesthesiology, the Medical School Hospital of Qingdao University.MATERIALS: Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents:homemade beat machine, ketamine hydrochloride (Hengrui Pharmaceutical Factory, Jiangsu), rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit (Boster Co.,Ltd.,Wuhan).METHODS: This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine (120 mg/kg) one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal

  13. Aquaporin 4 as a NH3 Channel.

    Science.gov (United States)

    Assentoft, Mette; Kaptan, Shreyas; Schneider, Hans-Peter; Deitmer, Joachim W; de Groot, Bert L; MacAulay, Nanna

    2016-09-01

    Ammonia is a biologically potent molecule, and the regulation of ammonia levels in the mammalian body is, therefore, strictly controlled. The molecular paths of ammonia permeation across plasma membranes remain ill-defined, but the structural similarity of water and NH3 has pointed to the aquaporins as putative NH3-permeable pores. Accordingly, a range of aquaporins from mammals, plants, fungi, and protozoans demonstrates ammonia permeability. Aquaporin 4 (AQP4) is highly expressed at perivascular glia end-feet in the mammalian brain and may, with this prominent localization at the blood-brain-interface, participate in the exchange of ammonia, which is required to sustain the glutamate-glutamine cycle. Here we observe that AQP4-expressing Xenopus oocytes display a reflection coefficient permeable water channels. PMID:27435677

  14. Clinical utility of testing AQP4-IgG in CSF

    Science.gov (United States)

    Majed, Masoud; Fryer, James P.; McKeon, Andrew; Lennon, Vanda A.

    2016-01-01

    Objective: To define, using assays of optimized sensitivity and specificity, the most informative specimen type for aquaporin-4 immunoglobulin G (AQP4-IgG) detection. Methods: Results were reviewed from longitudinal service testing for AQP4-IgG among specimens submitted to the Mayo Clinic Neuroimmunology Laboratory from 101,065 individual patients. Paired samples of serum/CSF were tested from 616 patients, using M1-AQP4-transfected cell-based assays (both fixed AQP4-CBA Euroimmun kit [commercial CBA] and live in-house flow cytometry [FACS]). Sensitivities were compared for 58 time-matched paired specimens (drawn ≤30 days apart) from patients with neuromyelitis optica (NMO) or high-risk patients. Results: The frequency of CSF submission as sole initial specimen was 1 in 50 in 2007 and 1 in 5 in 2015. In no case among 616 paired specimens was CSF positive and serum negative. In 58 time-matched paired specimens, AQP4-IgG was detected by FACS or by commercial CBA more sensitively in serum than in CSF (respectively, p = 0.06 and p 1:100 predicted CSF positivity (p < 0.001). The probability of CSF positivity was greater around attack time (p = 0.03). No control specimen from 128 neurologic patients was positive by either assay. Conclusions: FACS and commercial CBA detection of AQP4-IgG is less sensitive in CSF than in serum. The data suggest that most AQP4-IgG is produced in peripheral lymphoid tissues and that a critical serum/CSF gradient is required for IgG to penetrate the CNS in pathogenic quantity. Serum is the optimal and most cost-effective specimen for AQP4-IgG testing. Classification of evidence: This study provides Class IV evidence that for patients with NMO or NMOSD, CSF is less sensitive than serum for detection of AQP4-IgG. PMID:27144221

  15. Is Upregulation of Aquaporin 4-M1 Isoform Responsible for the Loss of Typical Orthogonal Arrays of Particles in Astrocytomas?

    Science.gov (United States)

    Fallier-Becker, Petra; Nieser, Maike; Wenzel, Ulrike; Ritz, Rainer; Noell, Susan

    2016-01-01

    The astrocytic endfoot membranes of the healthy blood-brain barrier-contacting the capillary-are covered with a large number of the water channel aquaporin 4 (AQP4). They form orthogonal arrays of particles (OAPs), which consist of AQP4 isoform M1 and M23. Under pathologic conditions, AQP4 is distributed over the whole cell and no or only small OAPs are found. From cell culture experiments, it is known that cells transfected only with AQP4-M1 do not form OAPs or only small ones. We hypothesized that in astrocytomas the situation may be comparable to the in vitro experiments expecting an upregulation of AQP4-M1. Quantitative Real-time PCR (qRT-PCR) of different graded astrocytomas revealed an upregulation of both isoforms AQP4 M1 and M23 in all astrocytomas investigated. In freeze fracture replicas of low-grade malignancy astrocytomas, more OAPs than in high-grade malignancy astrocytomas were found. In vitro, cultured glioma cells did not express AQP4, whereas healthy astrocytes revealed a slight upregulation of both isoforms and only a few OAPs in freeze fracture analysis. Taken together, we found a correlation between the decrease of OAPs and increasing grade of malignancy of astrocytomas but this was not consistent with an upregulation of AQP4-M1 in relation to AQP4 M23. PMID:27483250

  16. Phosphorylation in the C-terminal domain of Aquaporin-4 is required for Golgi transition in primary cultured astrocytes

    International Nuclear Information System (INIS)

    Aquaporin-4 (AQP4) is expressed in the perivascular and subpial astrocytes end-feet in mammalian brain, and plays a critical component of an integrated water and potassium homeostasis. Here we examine whether AQP4 is phosphorylated in primary cultured mouse astrocytes. Astrocytes were metabolically labeled with [32P]phosphoric acid, then AQP4 was immunoprecipitated with anti-AQP4 antibody. We observed that AQP4 was constitutively phosphorylated, which is reduced by treatment with protein kinase CK2 inhibitors. To elucidate the phosphorylation of AQP4 by CK2, myc-tagged wild-type or mutant AQP4 was transiently transfected in primary cultured astrocytes. Substitution of Ala residues for four putative CK2 phosphorylation sites in the C terminus abolished the phosphorylation of AQP4. Immunofluorescent microscopy revealed that the quadruple mutant was localized in the Golgi apparatus. These observations indicate that the C-terminal domain of AQP4 is constitutively phosphorylated at least in part by protein kinase CK2 and it is required for Golgi transition.

  17. Greatly attenuated experimental autoimmune encephalomyelitis in aquaporin-4 knockout mice

    Directory of Open Access Journals (Sweden)

    Verkman AS

    2009-08-01

    Full Text Available Abstract Background The involvement of astrocyte water channel aquaporin-4 (AQP4 in autoimmune diseases of the central nervous system has been suggested following the identification of AQP4 autoantibodies in neuromyelitis optica, an inflammatory demyelinating disease. Results We investigated the involvement of AQP4 in disease severity in an established mouse model of experimental autoimmune encephalomyelitis (EAE produced by immunization with myelin oligodendrocyte glycoprotein (MOG35–55 peptide. EAE was remarkably attenuated in AQP4 null mice compared to identically treated wildtype mice. Whereas most wildtype mice developed progressive tail and hindlimb paralysis, clinical signs were virtually absent in AQP4 null mice. Brain and spinal cords from AQP1 null mice showed greatly reduced mononuclear cell infiltration compared to wildtype mice, with relatively little myelin loss and axonal degeneration. Conclusion The reduced severity of autoimmune encephalomyelitis in AQP4 deficiency suggests AQP4 as a novel determinant in autoimmune inflammatory diseases of the central nervous system and hence a potential drug target.

  18. Curcumin alleviates brain edema by lowering AQP4 expression levels in a rat model of hypoxia-hypercapnia-induced brain damage

    OpenAIRE

    YU, LIN-SHENG; FAN, YAN-YAN; YE, GUANGHUA; Li, Junli; FENG, XIANG-PING; Lin, Kezhi; DONG, MIUWU; Wang, Zhenyuan

    2016-01-01

    The present study aimed to investigate the therapeutic effects of curcumin (CU) against brain edema in a rat model of hypoxia-hypercapnia (HH)-induced brain damage (HHBD). Male Sprague-Dawley rats were divided into five groups, including a control group and four treatment groups. The rats in the control group were raised under normal laboratory conditions and were injected with water, whereas the rats in the treatment groups were exposed to a low O2/high CO2 environment simulating HH conditio...

  19. A research update on the potential roles of aquaporin 4 in neuroinflammation.

    Science.gov (United States)

    Lan, Yu-Long; Fang, Deng-Yang; Zhao, Jie; Ma, Tong-Hui; Li, Shao

    2016-06-01

    The presence of aquaporins (AQPs) in the brain has led to intense research on the underlying roles of this family of proteins under both normal and pathological conditions. Aquaporin 4 (AQP4) is the major water-channel membrane protein expressed in the central nervous system (CNS), primarily in astrocytes. Emerging evidence suggests that AQP4 could play an important role in water and ion homeostasis in the brain, and it has been studied in various brain pathological conditions. However, far less is known about the potential for AQP4 to influence neuroinflammation and, furthermore, its potential role in neurodegenerative disorders such as Alzheimer's disease (AD). It has been suggested that the pathogenesis of many clinical diseases, such as neuromyelitis optica (NMO), multiple sclerosis (MS) and brain injuries, is related to the regulation of AQP4 expression. Investigating the effects of AQP4 on microglia and astrocytes could be important to understand its role in the pathogenesis of neuroinflammation. Although the exact roles of non-steroidal anti-inflammatory drugs (NSAIDs) in protection against the detrimental effects of neuroinflammation remain unclear, research into the possible neuroprotective effects of AQP4 against neuroinflammation regulation seems to be important for future investigations. PMID:26259614

  20. Aquaporin 9 in rat brain after severe traumatic brain injury

    OpenAIRE

    Hui Liu; Mei Yang; Guo-ping Qiu; Fei Zhuo; Wei-hua Yu; Shan-quan Sun; Yun Xiu

    2012-01-01

    OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9) in rat brain, after severe traumatic brain injury (TBI). METHODS: Brain water content (BWC), tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC), immunofluorescence (IF), western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest) peaks at 6 and 72 hours, and the blood brain barrier (BBB) was severely destroyed at six hours after ...

  1. 水通道蛋白4小RNA干扰技术优化亚低温治疗脑水肿%Optimized application of siRNA targeting aquaporin 4 with hypothermia treatment on cerebral edema following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    张赛; 刘晓智; 刘振林; 张文彬; 曲阳; 何敬; 孙世中

    2009-01-01

    目的 应用针对靶向水通道蛋白4(aquapofin 4,AQP-4)的小RNA(siRNA)干扰技术优化亚低温减轻颅脑创伤(traumatic brain injury,TBI)后脑水肿程度的治疗效果.方法 构建沉默AQP-4 mRNA表达的siRNA质粒;液压打击法建立大鼠TBI模型,分TBI对照组、AQP-4 siRNA治疗组、亚低温治疗组、AQP-4 siRNA及亚低温联合治疗组;提取第1、3、5、7天脑组织总RNA和总蛋白,RT-PCR和Western blot方法 检测AQP-4的mRNA和蛋白表达水平;干/湿比重法和Evans蓝测定法观察大鼠TBI后不同时相脑组织含水量和血脑屏障通透性改变;实验动物予以神经功能缺陷综合评分.结果 亚低温在减轻TBI后脑水肿程度方面优于AQP-4 siRNA,但siRNA技术在沉默AQP-4表达方面强于亚低温,联合应用AQP-4 siRNA和亚低温在TBI后降低脑水肿程度方面获得最佳治疗效果.结论 靶向AQP-4的Si RNA干扰技术可优化亚低温在TBI后降低脑水肿方面的治疗效果.%Objective To optimize the treatment effect of siRNA targeting aquaporin 4 with hypothermia on cerebral edema following traumatic brain injury. Methods To construct siRNA targeting aquaporin 4, and establish the TBI models in rats. The animals were divided into four groups: TBI group, AQP-4 siRNA group, hypothermia group, and combined group. To extract the total mRNA and proteins on the 1st, 3rd, 5th, and 7th day for RT-PCR and western blot analysis. The changes of brain water content and permeability of blood-brain barrier were measured by the methods of wet and dry weight and Evans blue fluorometry. All the rats were given a mark for their nerve function on the 7th day. Results Hypothermia treatment can obtain better effect than AQP-4 siRNA in lessening brain edema level. Meanwhile, siRNA treatment can obtain better effect than hypothermia group in silencing AQP-4 mRNA and protein expression. When combining hypothermia treatment with AQP-4 siRNA, we can obtain an optimized result than the single

  2. The central role of aquaporins in the pathophysiology of ischemic stroke

    Directory of Open Access Journals (Sweden)

    Jasmine eVella

    2015-04-01

    Full Text Available Stroke is a complex and devastating neurological condition with limited treatment options. Brain edema is a serious complication of ischemic stroke and early edema formation can significantly contribute to infarct formation and thus represents a promising target. Aquaporin (AQP water channels are contributors to water homeostasis by facilitating or impeding water transport and are consequently implicated in several disease pathways. At least 7 subtypes have been identified in the rodent brain and the use of transgenic mice has greatly aided our current understanding of the roles of these channels. AQP4, the most abundant channel in the brain is upregulated around the peri-infarct border in transient cerebral ischemia and AQP4 knockout mice demonstrate significantly reduced cerebral edema and improved neurological outcome. In models of vasogenic edema, brain swelling is more pronounced in AQP4 null mice than wildtype, providing strong evidence of the dual role of AQP4 in the formation and resolution of both vasogenic and cytotoxic edema. AQP4 is co-localized with inwardly rectifying K+ channels (Kir4.1 and glial K+ uptake is attenuated in AQP4 knockout mice compared to wildtype, indicating some form of functional interaction. AQP4-null mice also exhibit reduction in calcium signaling, suggesting that this channel may also be involved in triggering pathological downstream signaling events. Associations with gap junction protein Cx43 possibly reiterate its role in edema dissipation within the astroglial syncytium. Other roles ascribed to AQP4 include facilitation of astrocytic migration, glial scar formation, modulation of inflammation and signaling functions. Treatment of ischemic cerebral edema is based on the various mechanisms in which fluid content in different brain compartments can be modified. The identification of modulators and inhibitors of AQP4 offer new therapeutic avenues in the hope of reducing the extent of morbidity and mortality

  3. Immunohistochemical Localization of the Water Channels AQP4 and AQP5 in the Rat Pituitary Gland

    International Nuclear Information System (INIS)

    The pituitary gland is composed of the adenohypophysis and neurohypophysis. The adenohypophysis contains endocrine cells, folliculo-stellate (FS) cells, and marginal layer cells, whereas the neurohypophysis mainly comprises axons and pituicytes. To understand the molecular nature of water transfer in the pituitary gland, we examined the immunohistochemical localization of the membrane water channels aquaporin-4 (AQP4) and AQP5 in rat tissue. Double immunofluorescence analysis of AQP4 and S100 protein, a known marker for FS cells, marginal layer cells, and pituicytes, clearly revealed that FS cells and marginal layer cells in the adenohypophysis and the pituicytes in pars nervosa are positive for AQP4. AQP5 was found to be localized at the apical membrane in some marginal layer cells surrounding the Rathke’s residual pouch, in which AQP4 was observed to be localized on the basolateral membranes. These results suggest the following possibilities: 1) FS cells especially require water for their functions and 2) transepithelial water transfer could occur between the lumen of Rathke’s residual pouch and the interstitial fluid in the adenohypophysis through the AQP4 and AQP5 channels in the marginal layer cells

  4. Effects of propofol on neuronal apoptosis and aquaporin-4 expression in a rat model of traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Jianfang Song; Xiangyu Ji; Zangong Zhou

    2008-01-01

    BACKGROUND: Several studies have demonstrated that propofol exhibits protective effects in the central nervous system. OBJECTIVE: To observe the effects of propofol on neuronal apoptosis and aquaporin-4 (AQP-4) expression in a rat model of traumatic brain injury and to further investigate the mechanisms of action. DESIGN, TIME AND SETTING: The present neuronal, pathomorphological experiment was performed at the Institute of Cerebrovascular Disease, Qingdao University Medical College between April 2007 and March 2008. MATERIALS: Traumatic brain injury was induced by free falling objects in 150 healthy, male, Wistar rats. Propotol was produced by AstraZeaeca, China. Rabbit anti-rat AQP-4 polyclonal antibody, SABC inununohistochemistry kit, and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling (TUNEL) kit were purchased from Wuhan Boster Bioengineering Co., Ltd., China. METHODS: All 150 rats were randomly and evenly divided into lesion-only and propofol-treated groups. One hour after traumatic brain injury, propofol-treated animals received 1% propofol (10 mg/kg) through the caudal vein, followed by a sustained perfusion of 30 mg/kg propofol per hour for 2 hours, while the lesion-only group received equal volumes of physiological saline in parallel. MAIN OUTCOME MEASURES: At 6, 12, 24, 48, and 72 hours after traumatic brain injury, morphological changes in the peritraumatic and adjacent brain areas were analyzed in all rats by hematoxylin-eosin (HE) staining. In addition, cellular apoptosis was detected by TUNEL assay and the number of AQP-4-positive cells was determined by immunohistochemistry techniques. Brain water content was calculated as the ratio of dry to wet tissue weight. RESULTS: HE staining results demonstrated that, in the lesion-only group, the peritraumatic area exhibited neuronal and glial cell necrosis and disintegration. The adjacent area displayed swollen neuronal perikarya and vascular endothelial cells, cellular edema

  5. H95 Is a pH-Dependent Gate in Aquaporin 4.

    Science.gov (United States)

    Kaptan, Shreyas; Assentoft, Mette; Schneider, Hans Peter; Fenton, Robert A; Deitmer, Joachim W; MacAulay, Nanna; de Groot, Bert L

    2015-12-01

    Aquaporin 4 (AQP4) is a transmembrane protein from the aquaporin family and is the predominant water channel in the mammalian brain. The regulation of permeability of this protein could be of potential therapeutic use to treat various forms of damage to the nervous tissue. In this work, based on data obtained from in silico and in vitro studies, a pH sensitivity that regulates the osmotic water permeability of AQP4 is demonstrated. The results indicate that AQP4 has increased water permeability at conditions of low pH in atomistic computer simulations and experiments carried out on Xenopus oocytes expressing AQP4. With molecular dynamics simulations, this effect was traced to a histidine residue (H95) located in the cytoplasmic lumen of AQP4. A mutant form of AQP4, in which H95 was replaced with an alanine (H95A), loses sensitivity to cytoplasmic pH changes in in vitro osmotic water permeability, thereby substantiating the in silico work. PMID:26585511

  6. Longitudinally extensive transverse myelitis with AQP4 antibodies revealing ovarian teratoma.

    OpenAIRE

    Frasquet, M.; Bataller, L.; Torres-Vega, E.; Durán Moreno, María; García Verdugo, José Manuel; Sevilla, T; Rivas, Salvador; Pérez-Miralles, F.; Simó-Castelló, M.; Casanova, B.

    2013-01-01

    Paraneoplastic myelitis is a rare inflammatory disorder most frequently associated with solid tumors or lymphoproliferative disorders. Patients often harbor onconeuronal antibodies and their prognosis is usually poor. Here we report a 42-year old woman with longitudinally extensive transverse myelitis and aquaporin-4 (AQP4) antibodies that led to the diagnosis of ovarian teratoma. After tumor removal and immune therapy (including corticosteroids, plasma exchange, intravenous immunoglobulins a...

  7. Differential water permeability and regulation of three aquaporin 4 isoforms

    DEFF Research Database (Denmark)

    Fenton, Robert A.; Moeller, Hanne B; Zelenina, Marina;

    2010-01-01

    Aquaporin 4 (AQP4) is expressed in the perivascular glial endfeet and is an important pathway for water during formation and resolution of brain edema. In this study, we examined the functional properties and relative unit water permeability of three functional isoforms of AQP4 expressed...... in the brain (M1, M23, Mz). The M23 isoform gave rise to square arrays when expressed in Xenopus laevis oocytes. The relative unit water permeability differed significantly between the isoforms in the order of M1 > Mz > M23. None of the three isoforms were permeable to small osmolytes nor were they affected...... by changes in external K(+) concentration. Upon protein kinase C (PKC) activation, oocytes expressing the three isoforms demonstrated rapid reduction of water permeability, which correlated with AQP4 internalization. The M23 isoform was more sensitive to PKC regulation than the longer isoforms...

  8. Cerebrospinal fluid aquaporin-4-immunoglobulin G disrupts blood brain barrier.

    Science.gov (United States)

    Asgari, Nasrin; Berg, Carsten Tue; Mørch, Marlene Thorsen; Khorooshi, Reza; Owens, Trevor

    2015-08-01

    To clarify the significance of immunoglobulin G autoantibody specific for the astrocyte water channel aquaporin-4 in cerebrospinal fluid, aquaporin-4-immunoglobulin G from a neuromyelitis optica patient was administered intrathecally to naïve mice, and the distribution and pathogenic impact was evaluated. A distinct distribution pattern of aquaporin-4-immunoglobulin G deposition was observed in the subarachnoid and subpial spaces where vessels penetrate the brain parenchyma, via a paravascular route with intraparenchymal perivascular deposition. Perivascular astrocyte-destructive lesions were associated with blood-borne horseradish peroxidase leakage indicating blood-brain barrier breakdown. The cerebrospinal fluid aquaporin-4-immunoglobulin G therefore distributes widely in brain to initiate astrocytopathy and blood-brain barrier breakdown. PMID:26339679

  9. Fluid-percussion brain injury induces changes in aquaporin channel expression.

    Science.gov (United States)

    Oliva, A A; Kang, Y; Truettner, J S; Sanchez-Molano, J; Furones, C; Yool, A J; Atkins, C M

    2011-04-28

    Edema, the accumulation of excess fluid, is a major pathological change in the brain that contributes significantly to pathology and mortality after moderate to severe brain injury. Edema is regulated by aquaporin (AQP) channels which transport water across cellular membranes. Six AQPs are found in the brain (1, 3, 4, 5, 8, and 9), and previous studies have found that AQP4 is regulated after traumatic brain injury (TBI). To further understand how AQPs contribute to brain edema, we investigated whether expression of AQP1, 3, and 9 are also regulated after TBI. Adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury (FPI) or sham surgery. After induction of FPI, the injured, ipsilateral parietal cortex and hippocampus were dissected and analyzed by Western blotting. We observed a small decrease in AQP3 and 4 levels at 7 days after FPI in the ipsilateral, parietal cortex. Both AQP1 and 9 significantly increased within 30 min post-injury and remained elevated for up to 6 h in the ipsilateral, parietal cortex. Aqp1 and 9 mRNA levels were also significantly increased at 30 min post-FPI. Administration of an AQP1 and 4 antagonist, AqB013, non-significantly increased brain water content in sham, non-injured animals, and did not prevent edema formation 24 h after trauma in either the parietal cortex or hippocampus. These results indicate that Aqp1 and 9 mRNA and protein levels increase after moderate parasagittal FPI and that an inhibitor of AQP1 and 4 does not decrease edema after moderate parasagittal FPI. PMID:21329742

  10. Aquaporin-11 (AQP11) Expression in the Mouse Brain

    OpenAIRE

    Shin Koike; Yasuko Tanaka; Toshiyuki Matsuzaki; Yoshiyuki Morishita; Kenichi Ishibashi

    2016-01-01

    Aquaporin-11 (AQP11) is an intracellular aquaporin expressed in various tissues, including brain tissues in mammals. While AQP11-deficient mice have developed fatal polycystic kidneys at one month old, the role of AQP11 in the brain was not well appreciated. In this study, we examined the AQP11 expression in the mouse brain and the brain phenotype of AQP11-deficient mice. AQP11 messenger ribonucleic acid (mRNA) and protein were expressed in the brain, but much less than in the thymus and kidn...

  11. Water transport between CNS compartments: contributions of aquaporins and cotransporters

    DEFF Research Database (Denmark)

    MacAulay, N; Zeuthen, T

    2010-01-01

    hydrocephalus. The molecular pathways by which water molecules cross the cell membranes of the brain are not well-understood, although the discovery of aquaporin 4 (AQP4) in the brain improved our understanding of some of these transport processes, particularly under pathological conditions. In the present...... review we introduce another family of transport proteins as water transporters, namely the cotransporters and the glucose uniport GLUT1. In direct contrast to the aquaporins, these proteins have an inherent ability to transport water against an osmotic gradient. Some of them may also function as water...

  12. β-Dystroglycan cleavage by matrix metalloproteinase-2/-9 disturbs aquaporin-4 polarization and influences brain edema in acute cerebral ischemia.

    Science.gov (United States)

    Yan, W; Zhao, X; Chen, H; Zhong, D; Jin, J; Qin, Q; Zhang, H; Ma, S; Li, G

    2016-06-21

    Dystroglycan (DG) is widely expressed in various tissues, and throughout the cerebral microvasculature. It consists of two subunits, α-DG and β-DG, and the cleavage of the latter by matrix metalloproteinase (MMP)-2 and -9 underlies a number of physiological and pathological processes. However, the involvement of MMP-2/-9-mediated β-DG cleavage in cerebral ischemia remains uncertain. In astrocytes, DG is crucial for maintaining the polarization of aquaporin-4 (AQP4), which plays a role in the regulation of cytotoxic and vasogenic edema. The present study aimed to explore the effects of MMP-2/-9-mediated β-DG cleavage on AQP4 polarization and brain edema in acute cerebral ischemia. A model of cerebral ischemia was established via permanent middle cerebral artery occlusion (pMCAO) in male C57BL/6 mice. Western blotting, real-time polymerase chain reaction (PCR), immunohistochemical staining, immunofluorescent staining, electron microscopy, and light microscopy were used. Captopril was applied as a selective MMP-2/-9 inhibitor. Recombinant mouse MMP (rmMMP)-2 and -9 were used in an in vitro cleavage experiment. The present study demonstrated evidence of β-DG cleavage by MMP-2/-9 in pMCAO mouse brains; this cleavage was implicated in AQP4 redistribution and brain edema in cerebral ischemia. In addition, captopril exacerbated cytotoxic edema and ameliorated vasogenic edema at 24h after pMCAO, and alleviated brain edema and neurological deficit at 48h and 72h. In conclusion, this study provides novel insight into the effects of MMP-2/-9-mediated β-DG cleavage in acute cerebral ischemia. Such findings might facilitate the development of a therapeutic strategy for the optimization of MMP-2/-9 targeted treatment in cerebral ischemia. PMID:27038751

  13. Normal volumes and microstructural integrity of deep gray matter structures in AQP4+ NMOSD

    Science.gov (United States)

    Heine, Josephine; Pache, Florence; Lacheta, Anna; Borisow, Nadja; Kuchling, Joseph; Bellmann-Strobl, Judith; Ruprecht, Klemens; Brandt, Alexander U.; Paul, Friedemann

    2016-01-01

    Objective: To assess volumes and microstructural integrity of deep gray matter structures in a homogeneous cohort of patients with neuromyelitis optica spectrum disorder (NMOSD). Methods: This was a cross-sectional study including 36 aquaporin-4 antibody-positive (AQP4 Ab-positive) Caucasian patients with NMOSD and healthy controls matched for age, sex, and education. Volumetry of deep gray matter structures (DGM; thalamus, caudate, putamen, globus pallidus, hippocampus, amygdala, nucleus accumbens) was performed using 2 independent automated methods. Microstructural integrity was assessed based on diffusion tensor imaging. Results: Both volumetric analysis methods consistently revealed similar volumes of DGM structures in patients and controls without significant group differences. Moreover, no differences in DGM microstructural integrity were observed between groups. Conclusions: Deep gray matter structures are not affected in AQP4 Ab-positive Caucasian patients with NMOSD. NMOSD imaging studies should be interpreted with respect to Ab status, educational background, and ethnicity of included patients. PMID:27144219

  14. 脑出血患者血肿周围组织水通道蛋白-4表达与脑水肿及病理超微结构变化的关系%The relationship between the aquaporin-4 and brain edema, pathologic change, ultrastructure in perihematoma tissue in patients with intracerebral hemorrhage

    Institute of Scientific and Technical Information of China (English)

    郭富强; 吴文斌; 曾宪容; 唐建; 赵冬冬; YANG Zheng-lin; 杨果; 徐玉川; 陈隆益; 杨友松; 董凌琳; 代红源; 黄雨兰; 韦永胜; 李晓佳

    2008-01-01

    Objective To observe the expression of aquaporin-4 (AQP-4) mRNA and study the relationship between AQP-4,brain edema,pathological changes and uhrastructure of perihematoma tissue in intracerebral hemorrhage (ICH) patients.Methods Intracranial operation was performed via nonfunctional area with a funnel-like approach on 30 ICH patients.The brain tissue which must be removed 1 cm away the hematoma was removed within 12 hours for observation as normal brain tissue and taken as the control group (7 patients),and which of the brain tissue within 1 cm around hematoma was taken as the study specimens.The experimental group was subdivided into five groups according to the time interval after ICH;<6 hours (6 cases),6-12 hours (7 cases),12-24 hours (5 cases),24-72 hours (6 cases),and>72 hours (6 cases).Expression of the AQP-4 mRNA,brain edema,pathological and ultrastructural changes were observed with reverse transcription-polymerase chain reaction (RT-PCR),light microscope and electron microscope. Results The expression of the AQP-4 mRNA was not remarkable,the morphology and construction were basically normal in control group.The expression of AQP-4 mRNA was mild (1.17±0.41 ) and there was edema of neuroglia in the <6 hours group.After 6 hours,besides neuroglial edema,the expression of the AQP-4 mRNA was gradually obvious,capillary endothelial cells began to swell too,and tight junctions gradually began to loosen.In the 12 - 72 hours group the expression of the AQP-4 mRNA reached its peak (3.50 ± 0.55,3.60±0.55,both P< 0.01 ),and brain edema was most prominent,and electron microscopy showed that neurons,neuroglia,and capillary endothelial cells were markedly deformed.After 72 hours,the expression of AQP-4 mRNA gradually recovered,and brain cells showed less damage.On the 5th day the damage began to repair,and on the 8th day,the damage was basically repaired.The correlation analysis showed that there was a remarkable positive correlation between the expression of

  15. AQP4抗体阴性的NMO谱系疾病%Seronegative neuromyelitis optica spectrum disorder

    Institute of Scientific and Technical Information of China (English)

    曹珊珊; 魏世辉

    2015-01-01

    视神经脊髓炎(neuromyelitis optica,NMO)是一种严重的中枢神经系统脱髓鞘疾病,约90%的NMO和一半以上的NMO谱系疾病(neuromyelitis optica spectrum disorders,NMOSD)患者水通道蛋白4(aquaporin-4,AQP4)抗体阳性.AQP4抗体阴性相对于阳性患者更易好发于男性,在白种人中更常见,单时程,首发症状为双眼同时发作的视神经炎或脊髓炎,眼部损害较AQP4抗体阳性者轻.该抗体的检测方法主要有基于细胞的测定、酶联免疫吸附试验、免疫组织化学、放射免疫沉淀方法.%Neuromyelitis optica (NMO) is a severe demyelinating disease of the central nervous system.Approximately 90% of the patients with NMO and more than half of the patients with NMO spectrum disorders (NMODS) are positive for autoantibodies against aquaporin-4 (AQP4).The patients with AQP4 antibody-negative are characterized by more prone to male, a predominant Caucasian ethnicity, and an overrepresentation of simultaneous bilateral optic neuritis and transverse myelitis at first episode.Moreover, they experienced a better visual acuity at last follow-up compared with seropositive NMO.AQP4 were mainly tested by cell-based assay, enzyme linked immunosorbent assay, immunohistochemistry, radio-immunoprecipitation assay.

  16. 孕酮对大鼠脑挫裂伤后水通道蛋白-4与血脑屏障通透性的影响%The influence of progesteron on the changes of aquaporin-4 expression and blood-brain barrier permeability in rats after experimental contusion and laceration of brain

    Institute of Scientific and Technical Information of China (English)

    段永红; 谌南武; 汪丹; 杨咏梅; 廖勇仕; 梁日初; 舒毓高

    2009-01-01

    目的 探讨孕酮减轻创伤性脑水肿的机制.方法 建立雄性大鼠额叶脑挫裂伤模型并予孕酮干预治疗.免疫组织化学法检测脑组织星形胶质细胞AQP4表达的变化;伊文氏蓝法测定脑组织血脑屏障通透性的变化.结果 经孕酮干预治疗,脑组织含水量在各时相点均下降(P<0.05).脑挫裂伤后24、72、120 h时间段伤灶及其周边脑组织星形胶质细胞AQP4阳性细胞计数下降(P<0.05);伤后6 h和24 h EB含量明显下降(P<0.01).结论 孕酮减轻创伤性脑水肿的作用,可能与它降低外伤后脑组织AQP4表达水平和减轻伤后早期血脑屏障通透性有关.%Objective To discuss the mechanism of progesterone that soften brain water content in traumatic brain edema in rats. Methods The models of focal lobe contusion and laceration of brain were made on the male rats treated by the progesterone following injury. Immunohistochemical method was used to assess the expression of aquaporin-4 (AQP4). Evan's Blue method was used to detect the permeability of blood-brain barrier. Results Treated by the progesteron, the brain water content was significantly decreased, and the lower expression of AQP4 took place on astrocytes of the contusion and peri-contusion of the brain tissue after 24 h,72h ,and 120h . The content of EB was decreased at 6 h and 24 h post-injury. Conclusions Progesterone can soften the traumatic brain water content, which may be associated with the attenuation of AQP4 in frontal lobe contusion following traumatic brain injury ( TBI) and progesterone can protect the blood-brain barrier at early time after TBI.

  17. Aquaporin 9 in rat brain after severe traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hui Liu

    2012-03-01

    Full Text Available OBJECTIVE: To reveal the expression and possible roles of aquaporin 9 (AQP9 in rat brain, after severe traumatic brain injury (TBI. METHODS: Brain water content (BWC, tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC, immunofluorescence (IF, western blot, and real-time polymerase chain reaction were used. RESULTS: The BWC reached the first and second (highest peaks at 6 and 72 hours, and the blood brain barrier (BBB was severely destroyed at six hours after the TBI. The worst brain ischemia occurred at 72 hours after TBI. Widespread AQP9-positive astrocytes and neurons in the hypothalamus were detected by means of IHC and IF after TBI. The abundance of AQP9 and its mRNA increased after TBI and reached two peaks at 6 and 72 hours, respectively, after TBI. CONCLUSIONS: Increased AQP9 might contribute to clearance of excess water and lactate in the early stage of TBI. Widespread AQP9-positive astrocytes might help lactate move into neurons and result in cellular brain edema in the later stage of TBI. AQP9-positive neurons suggest that AQP9 plays a role in energy balance after TBI.

  18. Differences in distribution and regulation of astrocytic aquaporin-4 in human and rat hydrocephalic brain

    DEFF Research Database (Denmark)

    Skjolding, Anders Daehli; Holst, Anders Vedel; Broholm, Helle;

    2013-01-01

    human hydrocephalic cortex relative to controls was quantified by western blotting (n=28). A second biopsy (n=13) was processed for immunohistochemistry (GFAP, CD68, CD34 and aquaporin-4) and double immunofluorescence (aquaporin-4+GFAP and aquaporin-4+CD34). Brain tissue from human controls and kaolin...

  19. Phosphorylation of Ser-180 of rat aquaporin-4 shows marginal affect on regulation of water permeability: molecular dynamics study.

    Science.gov (United States)

    Sachdeva, Ruchi; Singh, Balvinder

    2014-04-01

    Water permeation through rat aquaporin-4 (rAQP4), predominantly found in mammalian brain is regulated by phosphorylation of Ser-180. The present study has been carried out to understand the structural mechanism of regulation of water permeability across the channel. Molecular dynamics (MD) simulations have been carried out to investigate the structural changes caused due to phosphorylation of Ser-180 in the tetrameric assembly of rAQP4 along with predicted C-terminal region (255-323). The interactions involving opposite charges are observed between cytoplasmic loops and the C-terminal region during MD simulations. This results in movement of C-terminal region of rAQP4 towards the cytoplasmic mouth of water channel. Despite this movement, there was a gap between C-terminal region and cytoplasmic mouth of the channel through which water molecules were able to gain entry into the channel. The interactions between C-terminus and loop D of neighboring monomers in a tetrameric assembly appear to prevent the complete closure of cytoplasmic mouth of the water channel. Further, the rates of water permeation through phosphorylated and unphosphorylated rAQP4 have also been compared. The simulation studies showed a continuous movement of water in a single file across pore of unphosphorylated as well as phosphorylated rAQP4. PMID:23651078

  20. The role of AQP4 in neuromyelitis optica: More answers, more questions.

    Science.gov (United States)

    Yang, Xin; Ransom, Bruce R; Ma, Jian-Fang

    2016-09-15

    Neuromyelitis optica (NMO) is a recurrent inflammatory disease that preferentially targets the optic nerves and spinal cord. The presence of antibodies to the water channel protein aquaporin-4 (AQP4), expressed almost exclusively in astrocytes in the central nervous system (CNS), is a reliable biomarker for NMO. These antibodies, NMO-IgG, may be responsible for the sequential cascade of immune events, including IgG/IgM deposition, infiltration of granulocytes and complement-mediated cytotoxicity (i.e. astrocyte loss) and demyelination. This review summarizes current thinking about the role of NMO-IgG in the pathogenesis of this condition. New insights were also generated along with important additional questions. PMID:27609277

  1. Investigating the effects of the cromakalim pretreatment on the expression of aquaporin -4 and the blood -brain barrier permeability in acute cerebral ischemia/reperfusion injury mice%克罗卡林预处理对脑缺血/再灌注大鼠水通道蛋白4表达及血脑屏障通透性的影响

    Institute of Scientific and Technical Information of China (English)

    王艳婷; 王士雷; 常庆显; 李瑜; 江岩; 王世端

    2010-01-01

    Objective To investigate the effects of ATP-sensitive potassium channel openers (Cromakalim) on the expression of aquaporin-4 and permeability of blood-brain barrer (BBB) after cerebral ischemic/repeffusion. Methods Thirty healthy male Wistar rats were randomized into three groups for different conditioning, the sham-operated group(A,n=10), the cerebral I/R group(B,n=10),and the cerebral I/R+Cromakalim group (C,n=10). Intraluminal suture methods were applied to establish the middle cerebral artery occlusion(MCAO) model with occlusion 2 h and reperfusion 24 h. The neurobehavioral function was evaluated with Bederson's test, and the pathological changes were observed with hematoxylin-eosin(HE) staining. The water content of brain was evaluated by wet-dry weight method, and the expressions of IgG and AQP-4 in brain were observed by immunohistochemistry staining. Results In comparison with group A's water content(78.2±1.3 )% and expressions of IgG and AQP-4 (0.0±0.0,13.6±1.5) ,the expressions of IgG and AQP-4(2.4±0.4,19.8±1.9) and the water content (81.3±1.2)% in group B both were significantly higher (P0.05),但IgG与AQP-4的表达(1.1±0.2,15.7±1.2)也明显升高(P<0.05);与B组相比,C组神经行为缺损评分明显减低(P<0.05),IgG、AQP-4(1.1±0.2,15.7±1.2)蛋白表达及脑组织含水量(79.5±0.6)%亦明显降低(P<0.05).结论 脑I/R损伤过程中,克罗卡林可能通过降低AQP-4的表达和BBB的通透性,减轻脑水肿,发挥脑保护作用.

  2. Effect of decompressive craniectomy on aquaporin-4 expression after lateral fluid percussion injury in rats.

    Science.gov (United States)

    Tomura, Satoshi; Nawashiro, Hiroshi; Otani, Naoki; Uozumi, Yoichi; Toyooka, Terushige; Ohsumi, Atsushi; Shima, Katsuji

    2011-02-01

    Decompressive craniectomy is one therapeutic option for severe traumatic brain injury (TBI), and it has long been used for the treatment of patients with malignant post-traumatic brain edema. A lack of definitive evidence, however, prevents physicians from drawing any conclusions about the effects of decompressive craniectomy for the treatment of TBI. Therefore, the aim of the present study was to investigate the influence of decompressive craniectomy on post-traumatic brain edema formation. The aquaporin-4 (AQP4) water channel is predominantly expressed in astrocytes, and it plays an important role in the regulation of brain water homeostasis. In the present study, we investigated the time course of AQP4 expression and the water content of traumatized cortex following decompressive craniectomy after TBI. Adult male Sprague-Dawley rats (300-400 g) were subjected to lateral fluid percussion injury using the Dragonfly device. The effect of decompressive craniectomy was studied in traumatized rats without craniectomy (closed skull, DC-), and in rats craniectomized immediately after trauma (DC+). AQP4 expression was investigated with a Western blot analysis and immunohistochemistry. Brain edema was measured using the wet weight/dry weight method. At 48 h after TBI, AQP4 expression of the DC- group was significantly increased compared with the DC+ group (p water content of the DC- group was significantly increased compared to the DC+ group at the same time point (p < 0.05). The present results suggest that decompressive craniectomy may affect AQP4 expression and reduce brain edema formation after TBI. PMID:21083433

  3. Studies on astrocyte function : potential roles in brain water homeostasis and neuroprotection

    OpenAIRE

    Song, Yutong

    2012-01-01

    Astrocytes are essential in brain homeostasis and function, including maintenance of water and ion balance. Astrocytes express the water channel aquaporin 4 (AQP4), implicated in both physiological functions and injury processes associated with brain edema, a common consequence of brain diseases. As part of the tripartite synapse astrocytes are tightly coupled to normal brain function via neuron-astrocyte interactions and by providing metabolic support to neurons as well as con...

  4. Correlation of AQP4 gene polymorphism with NMO clinical phenotypes and its underlying mechanism%AQP4基因多态性与NMO临床表型的相关性分析及功能研究

    Institute of Scientific and Technical Information of China (English)

    邱伟; 常艳宇; 李蕊; 龙友明; 黄建华; 麦卫华; 孙晓渤; 陆正齐; 胡学强

    2015-01-01

    目的 探讨水通道蛋白4(AQP4)基因多态性与国人视神经脊髓炎(NMO)发病的遗传相关性及分子机制.方法 收集2010年1月至2014年1月在中山大学附属第三医院神经科就诊的血清AQP4抗体(NMO-IgG)阳性的NMO患者111例及NMO谱系疾病(NMOSD)患者97例和健康对照204名作为研究对象.首先,选择AQP4基因调控区的8个单核苷酸多态性位点(SNP)进行基因分型;之后,通过关联分析SNP基因基因型与NMO临床表型的相关性;最后,利用双荧光素酶检测技术验证3'-非翻译区(3'-UTR)SNP位点的碱基改变对小分子RNA (miRNA)调控作用的影响.结果 AQP4基因3 '-UTR区rs1058424的A/T基因型(50.61%比70.45%,OR=0.430,95% CI 0.210~0.880)和rs3763043的C/T基因型(50.00%比68.18%,OR=0.467,95% CI 0.231 ~0.994)与长节段脊髓炎,3'-UTR区rs1058424的A/T基因型(46.72%比66.28%,OR=0.525,95% CI0.276~0.999)、rs335929的A/C基因型(45.08%比58.14%,OR=0.527,95% CI0.281 ~0.987)和启动子0区rs151244的C/T基因型(50.82%比69.77%,OR=0.450,95% CI 0.230 ~0.881)与视神经炎,3'-UTR区rs6508459及内含子区rs3763040基因型与合并系统性自身免疫性疾病存在相关性(P分别为0.012和0.023);miRNA 323-3p对AQP4基因表达有调控作用,但3'-UTR区rs1058424碱基改变并不影响miRNA 323-3p对AQP4基因的调控.结论 AQP4基因3'-UTR区的SNP与国人NMO临床表型具有相关性.miRNA 323-3p可能通过与AQP4基因3'-UTR区某一特定SNP位点结合起调节作用,从而参与NMO发病.%Objective To explore the correlation between aquaporin-4 (AQP4) gene single nucleotide polymorphism (SNP) and clinical phenotypes of neuromyelitis optica (NMO) and its underlying mechanism.Methods Eight SNPs in AQP4 gene regulatory region were selected and genotyped for 208 antiAQP4 autoantibodies (NMO-IgG) seropositive cases during January 2010 to January 2014 and 200 healthy subjects.Then the correlation was further analysed between

  5. Aquaporin-11: A channel protein lacking apparent transport function expressed in brain

    Directory of Open Access Journals (Sweden)

    Tsunenari Takashi

    2006-05-01

    Full Text Available Abstract Background The aquaporins are a family of integral membrane proteins composed of two subfamilies: the orthodox aquaporins, which transport only water, and the aquaglyceroporins, which transport glycerol, urea, or other small solutes. Two recently described aquaporins, numbers 11 and 12, appear to be more distantly related to the other mammalian aquaporins and aquaglyceroporins. Results We report on the characterization of Aquaporin-11 (AQP11. AQP11 RNA and protein is found in multiple rat tissues, including kidney, liver, testes and brain. AQP11 has a unique distribution in brain, appearing in Purkinje cell dendrites, hippocampal neurons of CA1 and CA2, and cerebral cortical neurons. Immunofluorescent staining of Purkinje cells indicates that AQP11 is intracellular. Unlike other aquaporins, Xenopus oocytes expressing AQP11 in the plasma membrane failed to transport water, glycerol, urea, or ions. Conclusion AQP11 is functionally distinct from other proteins of the aquaporin superfamily and could represent a new aquaporin subfamily. Further studies are necessary to elucidate the role of AQP11 in the brain.

  6. Aquaporins.

    Science.gov (United States)

    Echevarría, M; Ilundáin, A A

    1998-06-01

    Aquaporins (AQP) are members of the major intrinsic protein superfamily of integral membrane proteins, which function as specialized water channels to facilitate the passage of water through the cell membrane in animals, plants and bacterias. Ten AQP homologues named from 0 to 9 have been clones so far in mammals. They are widely distributed and more than one AQP could be present in the same cell. Most of the AQPs are only permeable to water and impermeable to small organic and inorganic molecules, except for AQP 3, 7 and 9 which are also permeable to urea and glycerol. From the hydrophobicity profile all AQPs seem to have six transmembrane domains with five connecting loops and with the amino and carboxyl termini in the cytoplasm. They are synthesized as monomers, but there is evidence suggesting that AQPs are formed in the membrane as tetrameric units, each of which has four water pores. The primary amino acid sequence contains putative phosphorylation sites for protein kinasses A and/or C or casein kinase II, and the expression and membrane protein abundance of some AQPs are known to be under hormonal regulation. The human genes for several AQPs have been cloned and an increasing number of disturbances associated to abnormal functioning of these proteins had been identified. PMID:9858131

  7. Aquaporin 4 expression and ultrastructure of the blood-brain barrier following cerebral contusion injury

    Institute of Scientific and Technical Information of China (English)

    Xinjun Li; Yangyun Han; Hong Xu; Zhongshu Sun; Zengjun Zhou; Xiaodong Long; Yumin Yang; Linbo Zou

    2013-01-01

    This study aimed to investigate aquaporin 4 expression and the ultrastructure of the blood-brain barrier at 2–72 hours following cerebral contusion injury, and correlate these changes to the formation of brain edema. Results revealed that at 2 hours after cerebral contusion and laceration injury, aquaporin 4 expression significantly increased, brain water content and blood-brain barrier permeability increased, and the number of pinocytotic vesicles in cerebral microvascular endothelial cells increased. In addition, the mitochondrial accumulation was observed. As contusion and laceration injury became aggravated, aquaporin 4 expression continued to increase, brain water content and blood-brain barrier permeability gradually increased, brain capillary endothelial cells and astrocytes swelled, and capillary basement membrane injury gradually increased. The above changes were most apparent at 12 hours after injury, after which they gradually attenuated. Aquaporin 4 expression positively correlated with brain water content and the blood-brain barrier index. Our experimental findings indicate that increasing aquaporin 4 expression and blood-brain barrier permeability after cerebral contusion and laceration injury in humans is involved in the formation of brain edema.

  8. Development of an Aquaporin-4 Orthogonal Array of Particle-Based ELISA for Neuromyelitis Optica Autoantibodies Detection.

    Directory of Open Access Journals (Sweden)

    Francesco Pisani

    Full Text Available Serological markers of Nuromyelitis Optica (NMO, an autoimmune disorder of the central nervous system, are autoantibodies targeting the astrocytic water channel aquaporin-4 (AQP4. We have previously demonstrated that the main epitopes for these autoantibodies (AQP4-IgG are generated by the supramolecular arrangement of AQP4 tetramers into an Orthogonal Array of Particles (OAPs. Many tests have been developed to detect AQP4-IgG in patient sera but several procedural issues affect OAP assembly and consequently test sensitivity. To date, the protein based ELISA test shows the lowest sensitivity while representing a valid alternative to the more sensitive cell based assay (CBA, which, however, shows economic, technical and interpretation problems. Here we have developed a high perfomance ELISA in which native OAPs are used as the molecular target. To this aim a native size exclusion chromatography method has been developed to isolate integral, highly pure and AQP4-IgG-recognized OAPs from rat brain. These OAPs were immobilized and oriented on a plastic plate by a sandwich approach and 139 human sera were tested, including 67 sera from NMO patients. The OAP-ELISA showed a 99% specificity and a higher sensitivity (91% compared to the CBA test. A comparative analysis revealed an end-point titer three orders of magnitude higher than the commercial ELISA and six times higher than our in-house CBA test. We show that CNS-extracted OAPs are crucial elements in order to perform an efficient AQP4-IgG test and the OAP-ELISA developed represents a valid alternative to the CBA currently used.

  9. Aquaporin-3 and aquaporin-4 are sorted differently and separately in the trans-Golgi network

    DEFF Research Database (Denmark)

    Christensen, Eva Arnspang; Sundbye, Sabrina Maria Gade; Nelson, W. James; Nejsum, Lene Niemann

    2013-01-01

    Aquaporin-3 (AQP3) and aquaporin-4 (AQP4) are homologous proteins expressed in the basolateral plasma membrane of kidney collecting duct principal cells, where they mediate the exit pathway for apically reabsorbed water. Although both proteins are localized to the same plasma membrane domain, it is...... unknown if they are sorted together in the Golgi, or arrive in the same or different vesicles at the plasma membrane. We addressed these questions using high resolution deconvolution imaging, spinning disk and laser scanning confocal microscopy of cells expressing AQP3 and AQP4. AQP3 and AQP4 were...... observed mostly in separate post-Golgi carriers, and spinning disk microscopy showed that most of AQP3 and AQP4 were delivered to the plasma membrane in separate vesicles. In contrast, VSV-G and LDL-R, two well-charcterized basolateral proteins, co-localized to a high degree in the same post-Golgi carriers...

  10. The Water Permeability and Pore Entrance Structure of Aquaporin-4 Depend on Lipid Bilayer Thickness.

    Science.gov (United States)

    Tong, Jihong; Wu, Zhe; Briggs, Margaret M; Schulten, Klaus; McIntosh, Thomas J

    2016-07-12

    Aquaporin-4 (AQP4), the primary water channel in glial cells of the mammalian brain, plays a critical role in water transport in the central nervous system. Previous experiments have shown that the water permeability of AQP4 depends on the cholesterol content in the lipid bilayer, but it was not clear whether changes in permeability were due to direct cholesterol-AQP4 interactions or to indirect effects caused by cholesterol-induced changes in bilayer elasticity or bilayer thickness. To determine the effects resulting only from bilayer thickness, here we use a combination of experiments and simulations to analyze AQP4 in cholesterol-free phospholipid bilayers with similar elastic properties but different hydrocarbon core thicknesses previously determined by x-ray diffraction. The channel (unit) water permeabilities of AQP4 measured by osmotic-gradient experiments were 3.5 ± 0.2 × 10(-13) cm(3)/s (mean ± SE), 3.0 ± 0.3 × 10(-13) cm(3)/s, 2.5 ± 0.2 × 10(-13) cm(3)/s, and 0.9 ± 0.1 × 10(-13) cm(3)/s in bilayers containing (C22:1)(C22:1)PC, (C20:1)(C20:1)PC, (C16:0)(C18:1)PC, and (C13:0)(C13:0)PC, respectively. Channel permeabilities obtained by molecular dynamics (MD) simulations were 3.3 ± 0.1 × 10(-13) cm(3)/s and 2.5 ± 0.1 × 10(-13) cm(3)/s in (C22:1)(C22:1)PC and (C14:0)(C14:0)PC bilayers, respectively. Both the osmotic-gradient and MD-simulation results indicated that AQP4 channel permeability decreased with decreasing bilayer hydrocarbon thickness. The MD simulations also suggested structural modifications in AQP4 in response to changes in bilayer thickness. Although the simulations showed no appreciable changes to the radius of the pore located in the hydrocarbon region of the bilayers, the simulations indicated that there were changes in both pore length and α-helix organization near the cytoplasmic vestibule of the channel. These structural changes, caused by mismatch between the hydrophobic length of AQP4 and the bilayer hydrocarbon

  11. Effect of lidocaine on retinal aquaporin-4 expression after ischemia/reperfusion injury in the rat

    Institute of Scientific and Technical Information of China (English)

    Liying He; Li Li

    2008-01-01

    BACKGROUND: Several studies have demonstrated that high doses of lidocaine can reduce edema in rats with brain injury by down-regulating aquaporin-4 (AQP4) expression. The hypothesis for the present study is that lidocaine could retinal edema that is associated with AQP4 expression.OBJECTIVE: This study was designed to investigate the interventional effects of lidocaine on retinal AQP4 expression and retinal edema following ischemia/reperfusion injury in the rat.DESIGN, TIME AND SETTING: This study, a randomized, controlled, animal experiment, was performed at the Basic Research Institute, Chongqing Medical University from September 2006 to May 2007.MATERIALS: Seventy-five, healthy, adult, female, Sprague-Dawley rats were included. A total of 50 rats were used to establish a retinal ischemia/reperfusion injury model using an anterior chamber enhancing perfusion unit. Rabbit anti-rat AQP4 antibody was purchased from Santa Cruz Biotechnology, USA.METHODS: All 75 rats were randomly divided into three groups, with 25 rats in each: control, model, and lidocaine. At each time point (1, 6, 12, 24, and 48 hours after modeling, five rats for each time point), each rat in the lidocaine group was intraperitoneally administered lidocaine with an initial dose of 30 mg/kg, followed by subsequent doses of 15 mg/kg every six hours. The entire treatment process lasted three days for each rat. At each above-mentioned time point, rats in the model group were modeled, but not administered any substances. Rats in the control group received the same treatments as in the lidocaine group except that lidocaine was replaceld by physiological saline.MAIN OUTCOME MEASURES: Following hematoxylin-eosin staining, rat retinal tissue was observed to investigate retinal edema degree through the use of an optical microscope and transmission electron microscope. Retinal AQP4 expression was determined by immunohistochemistry.RESULTS: At each above-mentioned time point, AQP4 expression was

  12. 姜黄素预处理对大鼠脑缺血/再灌注损伤后AQP-4及脑水肿的影响%Effects of chemical synthesized curcumin preconditioning on the expression of AQP-4 and cerebral edema after focal cerebral ischemia/reperfusion damage in rats

    Institute of Scientific and Technical Information of China (English)

    纪风涛; 曹铭辉; 梁建军; 刘玲; 李峰; 卜宪章

    2011-01-01

    Aim To explore the effect of chemical synthesized curcumin ( Cur) preconditioning on the expression of aquaporin 4 ( AQP-4 ) and cerebral edema after focal cerebral ischemia-reperfusion damage in rats. Methods Local ischemia/reperfusion model of middle cerebral artery occlusion ( MCAO) was made by inserting a nylon thread into internal caroticl artery in rats. 72 healthy SD rats weighing 290 ~310 g were randomly divided into 3 groups: sham operated group ( S) ( n = 18) , ischemia/reperfusion group (Ⅰ) ( n =18) , Cur group ( C1 and C2) (n = 18) which were preconditioned with cur 50 or 100 mg· kg-1 intraperitoneally 30 min before focal cerebral ischemia -reperfusion. In Ⅰ group , NS was given instead of Cur and in S group, the carotid arteries were exposed without performing MCAO. The rats in Ⅰ group ancl C1, C2 group were killed 24 hours after cerebral ischemia/reperfusion. Neurological scores were studied , method of dry/wet weight was used to observe water content , and Evans Blue( EB) was collected to observe the changes of blood-brain barrier ( BBB) permeability. Expression of AQP-4 ancl activation of c-Jun N-terminal kinase ( JNK) in rat brain were determined by Western blot.Results Sham operated group presented no neurological changes. The water content and EB in C1 and C2 group were significantly lower than those of Ⅰ group ( P < 0. 05 ) . Curcumin could also alleviate the expression of AQP-4 and the phosphorylation of JNK (P < 0. 05 ) . The neurological deficiency scores in C1 and C2 groups were obviously higher than those of I group ( P < 0. 05 ) . Conclusions Chemical synthesized curcurmn can alleviate the expression of AQP-4 and the phosphorylation of JNK , therefore protect the structure of BBB and alleviate the cerebral eclema which can exert the neuroprotective effect after focal cerebral ischemia ancl reperfusion.%目的 研究化学合成的姜黄素预处理对大鼠脑缺血/再灌注损伤后AQP-4及脑水肿的影响.方法 采

  13. Cerebrospinal fluid aquaporin-4-immunoglobulin G disrupts blood brain barrier

    DEFF Research Database (Denmark)

    Asgari, Nasrin; Berg, Carsten Tue; Mørch, Marlene Thorsen;

    2015-01-01

    To clarify the significance of immunoglobulin G autoantibody specific for the astrocyte water channel aquaporin-4 in cerebrospinal fluid, aquaporin-4-immunoglobulin G from a neuromyelitis optica patient was administered intrathecally to naïve mice, and the distribution and pathogenic impact was...

  14. Challenging AQP4 druggability for NMO-IgG antibody binding using molecular dynamics and molecular interaction fields.

    Science.gov (United States)

    Mangiatordi, Giuseppe Felice; Alberga, Domenico; Siragusa, Lydia; Goracci, Laura; Lattanzi, Gianluca; Nicolotti, Orazio

    2015-07-01

    Neuromyelitis optica (NMO) is a multiple sclerosis-like immunopathology disease affecting optic nerves and the spinal cord. Its pathological hallmark is the deposition of a typical immunoglobulin, called NMO-IgG, against the water channel Aquaporin-4 (AQP4). Preventing NMO-IgG binding would represent a valuable molecular strategy for a focused NMO therapy. The recent observation that aspartate in position 69 (D69) is determinant for the formation of NMO-IgG epitopes prompted us to carry out intensive Molecular Dynamics (MD) studies on a number of single-point AQP4 mutants. Here, we report a domino effect originating from the point mutation at position 69: we find that the side chain of T62 is reoriented far from its expected position leaning on the lumen of the pore. More importantly, the strength of the H-bond interaction between L53 and T56, at the basis of the loop A, is substantially weakened. These events represent important pieces of a clear-cut mechanistic rationale behind the failure of the NMO-IgG binding, while the water channel function as well as the propensity to aggregate into OAPs remains unaltered. The molecular interaction fields (MIF)-based analysis of cavities complemented MD findings indicating a putative binding site comprising the same residues determining epitope reorganization. In this respect, docking studies unveiled an intriguing perspective to address the future design of small drug-like compounds against NMO. In agreement with recent experimental observations, the present study is the first computational attempt to elucidate NMO-IgG binding at the molecular level, as well as a first effort toward a less elusive AQP4 druggability. PMID:25839357

  15. Status of diagnostic approaches to AQP4-IgG seronegative NMO and NMO/MS overlap syndromes.

    Science.gov (United States)

    Juryńczyk, Maciej; Weinshenker, Brian; Akman-Demir, Gulsen; Asgari, Nasrin; Barnes, David; Boggild, Mike; Chaudhuri, Abhijit; D'hooghe, Marie; Evangelou, Nikos; Geraldes, Ruth; Illes, Zsolt; Jacob, Anu; Kim, Ho Jin; Kleiter, Ingo; Levy, Michael; Marignier, Romain; McGuigan, Christopher; Murray, Katy; Nakashima, Ichiro; Pandit, Lekha; Paul, Friedemann; Pittock, Sean; Selmaj, Krzysztof; de Sèze, Jérôme; Siva, Aksel; Tanasescu, Radu; Vukusic, Sandra; Wingerchuk, Dean; Wren, Damian; Leite, Isabel; Palace, Jacqueline

    2016-01-01

    Distinguishing aquaporin-4 IgG(AQP4-IgG)-negative neuromyelitis optica spectrum disorders (NMOSD) from opticospinal predominant multiple sclerosis (MS) is a clinical challenge with important treatment implications. The objective of the study was to examine whether expert clinicians diagnose and treat NMO/MS overlapping patients in a similar way. 12 AQP4-IgG-negative patients were selected to cover the range of clinical scenarios encountered in an NMO clinic. 27 NMO and MS experts reviewed their clinical vignettes, including relevant imaging and laboratory tests. Diagnoses were categorized into four groups (NMO, MS, indeterminate, other) and management into three groups (MS drugs, immunosuppression, no treatment). The mean proportion of agreement for the diagnosis was low (p o = 0.51) and ranged from 0.25 to 0.73 for individual patients. The majority opinion was divided between NMOSD versus: MS (nine cases), monophasic longitudinally extensive transverse myelitis (LETM) (1), acute disseminated encephalomyelitis (ADEM) (1) and recurrent isolated optic neuritis (RION) (1). Typical NMO features (e.g., LETM) influenced the diagnosis more than features more consistent with MS (e.g., short TM). Agreement on the treatment of patients was higher (p o = 0.64) than that on the diagnosis with immunosuppression being the most common choice not only in patients with the diagnosis of NMO (98 %) but also in those indeterminate between NMO and MS (74 %). The diagnosis in AQP4-IgG-negative NMO/MS overlap syndromes is challenging and diverse. The classification of such patients currently requires new diagnostic categories, which incorporate lesser degrees of diagnostic confidence. Long-term follow-up may identify early features or biomarkers, which can more accurately distinguish the underlying disorder. PMID:26530512

  16. Effect of colostrum and milk on small intestine expression of AQP4 and AQP5 in newborn buffalo calves.

    Science.gov (United States)

    Squillacioti, C; De Luca, A; Pero, M E; Vassalotti, G; Lombardi, P; Avallone, L; Mirabella, N; Pelagalli, A

    2015-12-01

    Functional studies indicate differences in newborn gastrointestinal morphology and physiology after a meal. Both water and solutes transfer across the intestinal epithelial membrane appear to occur via aquaporins (AQPs). Given that the physiological roles of AQP4 and AQP5 in the developing intestine have not been fully established, the objective of this investigation was to determine their distribution, expression and respective mRNA in the small intestine of colostrums-suckling buffalo calves by using immunohistochemistry, Western blot, and reverse transcriptase-PCR analysis. Results showed different tissue distribution between AQP4 and AQP5 with the presence of the former along the enteric neurons and the latter in the endocrine cells. Moreover, their expression levels were high in the ileum of colostrum-suckling buffalo calves. The data present a link between feeding, intestinal development and water homeostasis, suggesting the involvement of these channel proteins in intestinal permeability and fluid secretion/absorption during this stage of development after birth. PMID:26679810

  17. Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis

    DEFF Research Database (Denmark)

    Jarius, Sven; Frederiksen, Jette Lautrup Battistini; Waters, Patrick; Paul, Friedemann; Akman-Demir, Gulsen; Marignier, Romain; Franciotta, Diego; Ruprecht, Klemens; Kuenz, Bettina; Rommer, Paulus; Kristoferitsch, Wolfgang; Wildemann, Brigitte; Vincent, Angela

    Antibodies to aquaporin-4 (AQP4-Ab) are found in 60-80% of patients with neuromyelitis optica (NMO), a severely disabling inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the optic nerves and spinal cord.......Antibodies to aquaporin-4 (AQP4-Ab) are found in 60-80% of patients with neuromyelitis optica (NMO), a severely disabling inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the optic nerves and spinal cord....

  18. Frequency and prognostic impact of antibodies to aquaporin-4 in patients with optic neuritis

    DEFF Research Database (Denmark)

    Jarius, Sven; Frederiksen, Jette Lautrup Battistini; Waters, Patrick;

    2010-01-01

    Antibodies to aquaporin-4 (AQP4-Ab) are found in 60-80% of patients with neuromyelitis optica (NMO), a severely disabling inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the optic nerves and spinal cord.......Antibodies to aquaporin-4 (AQP4-Ab) are found in 60-80% of patients with neuromyelitis optica (NMO), a severely disabling inflammatory CNS disorder of putative autoimmune aetiology, which predominantly affects the optic nerves and spinal cord....

  19. Aquaporin-4-Immunoglobulin G-autoimmune syndrome in a Paraneoplastic Context

    DEFF Research Database (Denmark)

    Soelberg, Kerstin; Grauslund, Jakob; Lillevang, Søren Thue;

    Background: Serum autoantibody against the astrocytic water channel aquaporin 4 (AQP4-IgG) is a biomarker for neuromyelitis optica spectrum disorder (NMOSD). In some patients the presence of AQP4-IgG reflects a tumor-driven immune response. Methods: AQP4-IgG was measured with a recombinant...... case suggests that AQP4 autoimmunity may in some cases have a paraneoplastic basis. 1. Asgari N, Nielsen C, Stenager E, Kyvik KO, Lillevang ST. HLA, PTPN22 and PD-1 associations as markers of autoimmunity in neuromyelitis optica. Multiple Sclerosis. 2012;18(1):23-30....

  20. 氯胺酮预处理对大鼠局灶性脑缺血/再灌注损伤后脑水肿和水通道蛋白4表达的影响%The effects of ketamine pretreated on cerebral edema and AQP4 expression after transient focal cerebral ischemia/reperfusion in rats

    Institute of Scientific and Technical Information of China (English)

    蔡淑女; 祝胜美

    2010-01-01

    目的 观察氯胺酮缺血前预给药对大鼠短暂性脑缺血/再灌注损伤后神经缺失症状、脑水肿及Aquaporin 4(AQP4)表达的影响.方法 62只健康雄性Sprague-Dawley大鼠,体重220~250 g,随机分为假手术组(Sham组,n=18只)、生理盐水组(Vehicle组,n=22只)和氯胺酮预处理组(Ketamine组,n=22只).Vehicle组、Ketamine组大鼠采用线栓法阻塞大鼠右侧大脑中动脉,90 min后拔出栓线实现再灌注,建立局灶性脑缺血/再灌注模型.Ketamine组、Vehicle组分别于缺血前30min静脉持续输注(1mg·kg-1·min-1)5%氯胺酮及0.9%生理盐水,30 min后实施缺血再灌注损伤.Sham组手术操作同前,但线栓未阻塞大脑中动脉.再灌注24 h大鼠进行神经缺失症状评分,后断头取脑,采用干湿重法测定缺血侧脑半球的水肿度,Western-blot检测缺血周边区脑组织AQP4表达.结果 Vehicle组、Ketamine组大鼠脑缺血/再灌注损伤后神经功能缺失症状明显,缺血侧脑半球干湿重比值较Sham组明显增加(P0.05).与Sham组相比,Vehicle组、Ketamine组大鼠脑缺血/再灌注损伤后缺血周边区AQP4表达明显上调(P0.05).结论 大鼠脑缺血/再灌注损伤后神经功能缺失症状及脑水肿明显,缺血周边区脑组织AQP4表达上调;氯胺酮缺血前预处理未能明显改善神经缺失症状及脑水肿,对缺血周边区脑组织AQP4的表达无影响.%Objective To investigate the effects of ketamine pretreatment on cerebral edema following brain ischemia reperfusion injury in rats and assess the involvement of Aquaporin 4(AQP4) expression.Methods Sixty-two healthy male Sprague-Dawley rats weighing 220-250 g were randomly divided into 3 groups:sham operation group(group Sham,n=18);saline group(group Vehicle,n=22);ketamine pretreatment group(group Ketamine,n=22).The transient focal ischemia/reperfusion was induced by introducing a silicone-coated monofilament nylon suture from the right external carotid artery into the origin

  1. A correlative study between the expression of aquaporin-4 and molecular mechanism of MR diffusion weighted imaging after the hepatic failure in rats

    International Nuclear Information System (INIS)

    Objective; To investigate the rule of the cerebral tissues aquaporin-4 (AQP4) expression in acute and chronic hepatic failure mice. To study the molecular biologic mechanism of the diffusion weighted imaging (DWI). Methods: Sixty five male Spragne-Dawley rats were divided into 3 groups randomly, including acutte (n=25), chronic hepatic failure (n=25) and control group (n=15). Thioacetamide (TAA) intraperitoneal injection produces the acute and chronic hepatic failure models. All rats in groups were examined with MR DWI. We Observed the distribution of abnormal signal on DWI. The DWI single values of top and lateral cortex of parietal lobe, peripheral region of lateral ventricle in the highest hyperintensity section of brain were measured. Blood ammonia values were examined. The pathologic and immuno- histochemistry and RT-PCR examination for brain specimen were performed. All date were analyzed with statistical methods. Results: The mean values of blood ammonia were significantly different (P0.05). Conclusions: Increase of the blood ammonia was the main cause for the brain energy metabolic abnormality and AQP-4 mRNA and protein expression. The hyperammonemia was the key factor in the occurrence and development of the hepatic brain edema. The abnormal findings in DWI signal could reflect the range and degree of the brain edema and AQP-4 protein expression. (authors)

  2. Negative impact of AQP-4 channel inhibition on survival of retinal ganglion cells and glutamate metabolism after crushing optic nerve.

    Science.gov (United States)

    Nishikawa, Yuko; Oku, Hidehiro; Morishita, Seita; Horie, Taeko; Kida, Teruyo; Mimura, Masashi; Fukumoto, Masanori; Kojima, Shota; Ikeda, Tsunehiko

    2016-05-01

    The purpose of this study was to determine whether inhibition of aquaporin 4 (AQP4) is neuroprotective or neurodestructive after crushing the optic nerve of rats. The left optic nerves of rats were crushed, and TGN-020 (5.0 mg/kg, crush TGN-020) or its vehicle (DMSO, crush placebo) was injected intraperitoneally just after the crushing. As controls, the left optic nerves were exposed but not touched in other rats (sham controls). The retinal damages were determined by the density of retinal ganglion cells (RGCs) and the ratio of BAX/Bcl-2 on day 7. The glutamate level in the optic nerve on day 1 after the crushing was determined. The expressions of glutamine synthetase, glutamate-aspartate transporter (GLAST), and AQP4 were determined on day 3 by immunoblotting. The effects of AQP4 inhibition on the glutamate-induced changes of AQP4 expression and on the glutamate uptake were determined for optic nerve astrocytes in culture. The results showed that the density of RGCs was 2040 ± 91.3 cells/mm(2) (n = 6) in the sham control, and it was significantly decreased to 1072 ± 134.3 cells/mm(2) after crushing the optic nerve (P crush placebo, n = 7; Fisher). An intraperitoneal injection of TGN-020 led to a further significant (P = 0.02, Fisher) decrease of the density of RGCs to 743 ± 371 cells/mm(2) (crush TGN-020, n = 7). The mRNA level of BAX/Bcl-2 ratio was 0.37 ± 0.05 in the sham control (n = 6) which was significantly increased to 0.88 ± 0.10 after crushing the optic nerve (placebo crush, n = 7; P = 0.0001, Scheffe). TGN-020 also significantly increased the BAX/Bcl-2 ratio to 1.29 ± 0.4 (n = 6) from the crush placebo group (P = 0.04, Scheffe). Immunoblotting showed similar changes in the protein levels. The glutamate level in the optic nerve was significantly increased to 53.7 ± 6.0 μM/mg/protein on day 1 (n = 4) from the sham control level of 45.9 ± 3.1 μM/mg/protein (n = 4; P = 0.04, t test). TGN-020

  3. Detection of aquaporin-4 antibody using aquaporin-4 extracellular loop-based carbon nanotube biosensor for the diagnosis of neuromyelitis optica.

    Science.gov (United States)

    Son, Manki; Kim, Daesan; Park, Kyung Seok; Hong, Seunghun; Park, Tai Hyun

    2016-04-15

    Here we propose a carbon nanotube (CNT) field-effect transistor (FET) functionalized with aquaporin-4 (AQP4) extracellular loop peptides for the rapid detection of AQP4 antibody without pretreatment. Neuromyelitis optica (NMO) is a rare disease of the central nerve system that affects the optic nerves and the spinal cord. NMO-IgG, a serum antibody in patients, is highly specific for NMO and targets AQP4. We synthesized AQP4 extracellular loop peptides, known as primary autoimmune target in NMO, and immobilized them onto CNT-FET. The sensor showed p-type FET characteristics after the functionalization of peptides. The sensor was able to detect antibody with a detection limit of 1 ng l(-1). Moreover, AQP4 antibody in human serum was detected without any pretreatment. These results indicate that the biosensor can be used for rapid and simple detection of NMO antibody. PMID:26594890

  4. Brain MRI abnormalities in neuromyelitis optica

    International Nuclear Information System (INIS)

    Objective: The purpose of this study was to explore brain MRI findings in neuromyelitis optica (NMO) and to investigate specific brain lesions with respect to the localization of aquaporin-4 (AQP-4). Materials and methods: Forty admitted patients (36 women) who satisfied the 2006 criteria of Wingerchuk et al. for NMO were included in this study. All patients received a neurological examination and MRI scanning including brain and spinal cord. MRIs were classified as normal, nonspecific, multiple sclerosis-like, typical abnormalities. MS-like lesions were too few to satisfy the Barkhof et al. criteria for MS. Confluent lesions involving high AQP-4 regions were considered typical. Non-enhancing deep white matter lesions other than MS-like lesions or typical lesions were classified as nonspecific. Results: Brain MRI lesions were delineated in 12 patients (25%). Four patients (10%) had hypothalamus, brainstem or periventricle lesions. Six (15%) patients were nonspecific, and 2 (5%) patients had multiple sclerosis-like lesions. Conclusion: Brain MRIs are negative in most NMO, and brain lesions do not exclude the diagnosis of NMO. Hypothalamus, brainstem or periventricle lesions, corresponding to high sites of AQP-4 in the brain, are indicative of lesions of NMO.

  5. Brain MRI abnormalities in neuromyelitis optica

    Energy Technology Data Exchange (ETDEWEB)

    Wang Fei, E-mail: feiwang1973@gmail.com [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Liu Yaou, E-mail: asiaeurope80@gmail.com [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Duan Yunyun, E-mail: duanyun2003@sohu.com [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Li Kuncheng, E-mail: kunchengli@yahoo.com.cn [Department of Radiology, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China); Education Ministry Key Laboratory for Neurodegenerative Disease, Xuanwu Hospital, Capital University of Medical Sciences, 45 Chang-Chun St, Xuanwu District, Beijing 100053 (China)

    2011-11-15

    Objective: The purpose of this study was to explore brain MRI findings in neuromyelitis optica (NMO) and to investigate specific brain lesions with respect to the localization of aquaporin-4 (AQP-4). Materials and methods: Forty admitted patients (36 women) who satisfied the 2006 criteria of Wingerchuk et al. for NMO were included in this study. All patients received a neurological examination and MRI scanning including brain and spinal cord. MRIs were classified as normal, nonspecific, multiple sclerosis-like, typical abnormalities. MS-like lesions were too few to satisfy the Barkhof et al. criteria for MS. Confluent lesions involving high AQP-4 regions were considered typical. Non-enhancing deep white matter lesions other than MS-like lesions or typical lesions were classified as nonspecific. Results: Brain MRI lesions were delineated in 12 patients (25%). Four patients (10%) had hypothalamus, brainstem or periventricle lesions. Six (15%) patients were nonspecific, and 2 (5%) patients had multiple sclerosis-like lesions. Conclusion: Brain MRIs are negative in most NMO, and brain lesions do not exclude the diagnosis of NMO. Hypothalamus, brainstem or periventricle lesions, corresponding to high sites of AQP-4 in the brain, are indicative of lesions of NMO.

  6. 1,3-propanediol binds deep inside the channel to inhibit water permeation through aquaporins.

    Science.gov (United States)

    Yu, Lili; Rodriguez, Roberto A; Chen, L Laurie; Chen, Liao Y; Perry, George; McHardy, Stanton F; Yeh, Chih-Ko

    2016-02-01

    Aquaporins and aquaglyceroporins (AQPs) are membrane channel proteins responsible for transport of water and for transport of glycerol in addition to water across the cell membrane, respectively. They are expressed throughout the human body and also in other forms of life. Inhibitors of human AQPs have been sought for therapeutic treatment for various medical conditions including hypertension, refractory edema, neurotoxic brain edema, and so forth. Conducting all-atom molecular dynamics simulations, we computed the binding affinity of acetazolamide to human AQP4 that agrees closely with in vitro experiments. Using this validated computational method, we found that 1,3-propanediol (PDO) binds deep inside the AQP4 channel to inhibit that particular aquaporin efficaciously. Furthermore, we used the same method to compute the affinities of PDO binding to four other AQPs and one aquaglyceroporin whose atomic coordinates are available from the protein data bank (PDB). For bovine AQP1, human AQP2, AQP4, AQP5, and Plasmodium falciparum PfAQP whose structures were resolved with high resolution, we obtained definitive predictions on the PDO dissociation constant. For human AQP1 whose PDB coordinates are less accurate, we estimated the dissociation constant with a rather large error bar. Taking into account the fact that PDO is generally recognized as safe by the US FDA, we predict that PDO can be an effective diuretic which directly modulates water flow through the protein channels. It should be free from the serious side effects associated with other diuretics that change the hydro-homeostasis indirectly by altering the osmotic gradients. PMID:26481430

  7. Structural Determinants of Oligomerization of the Aquaporin-4 Channel.

    Science.gov (United States)

    Kitchen, Philip; Conner, Matthew T; Bill, Roslyn M; Conner, Alex C

    2016-03-25

    The aquaporin (AQP) family of integral membrane protein channels mediate cellular water and solute flow. Although qualitative and quantitative differences in channel permeability, selectivity, subcellular localization, and trafficking responses have been observed for different members of the AQP family, the signature homotetrameric quaternary structure is conserved. Using a variety of biophysical techniques, we show that mutations to an intracellular loop (loop D) of human AQP4 reduce oligomerization. Non-tetrameric AQP4 mutants are unable to relocalize to the plasma membrane in response to changes in extracellular tonicity, despite equivalent constitutive surface expression levels and water permeability to wild-type AQP4. A network of AQP4 loop D hydrogen bonding interactions, identified using molecular dynamics simulations and based on a comparative mutagenic analysis of AQPs 1, 3, and 4, suggest that loop D interactions may provide a general structural framework for tetrameric assembly within the AQP family. PMID:26786101

  8. Pathophysiology of Juvenile Traumatic Brain Injury: Role of Edema and a Potential Treatment

    OpenAIRE

    Adami, Arash

    2013-01-01

    Traumatic brain injury (TBI) is caused by an external force to the head, resulting in damage to the brain. TBI is especially common in children and young adults and is associated with long-term mortality and morbidity. Juveniles seem to be at increased risk of developing cerebral edema after TBI partly due to higher water content and developmental differences in the brain's response to injury. Aquaporin-4 (AQP4) is the most abundant water channel in the brain and plays a critical role in edem...

  9. Cortical astrogliosis and increased perivascular aquaporin-4 in idiopathic intracranial hypertension.

    Science.gov (United States)

    Eide, Per Kristian; Eidsvaag, Vigdis Andersen; Nagelhus, Erlend A; Hansson, Hans-Arne

    2016-08-01

    The syndrome idiopathic intracranial hypertension (IIH) includes symptoms and signs of raised intracranial pressure (ICP) and impaired vision, usually in overweight persons. The pathogenesis is unknown. In the present prospective observational study, we characterized the histopathological changes in biopsies from the frontal brain cortical parenchyma obtained from 18 IIH patients. Reference specimens were sampled from 13 patients who underwent brain surgery for epilepsy, tumors or acute vascular diseases. Overnight ICP monitoring revealed abnormal intracranial pressure wave amplitudes in 14/18 IIH patients, who underwent shunt surgery and all responded favorably. A remarkable histopathological observation in IIH patients was patchy astrogliosis defined as clusters of hypertrophic astrocytes enclosing a nest of nerve cells. Distinct astrocyte domains (i.e. no overlap between astrocyte processes) were lacking in most IIH biopsy specimens, in contrast to their prevalence in reference specimens. Evidence of astrogliosis in IIH was accompanied with significantly increased aquaporin-4 (AQP4) immunoreactivity over perivascular astrocytic endfeet, compared to the reference specimens, measured with densitometry. Scattered CD68 immunoreactive cells (activated microglia and macrophages) were recognized, indicative of some inflammation. No apoptotic cells were demonstrable. We conclude that the patchy astrogliosis is a major finding in patients with IIH. We propose that the astrogliosis impairs intracranial pressure-volume reserve capacity, i.e. intracranial compliance, and contributes to the IIH by restricting the outflow of fluid from the cranium. The increased perivascular AQP4 in IIH may represent a compensatory mechanism to enhance brain fluid drainage. PMID:27188961

  10. Anti-Aquaporin-4 Antibody-Positive Neuromyelitis Optica Presenting with Syndrome of Inappropriate Antidiuretic Hormone Secretion as an Initial Manifestation

    Directory of Open Access Journals (Sweden)

    H. Nakajima

    2011-10-01

    Full Text Available The distribution of neuromyelitis optica (NMO-characteristic brain lesions corresponds to sites of high aquaporin-4 (AQP4 expression, and the brainstem and hypothalamus lesions that express high levels of AQP4 protein are relatively characteristic of NMO. The syndrome of inappropriate antidiuretic hormone secretion (SIADH is one of the important causes of hyponatremia and results from an abnormal production or sustained secretion of antidiuretic hormone (ADH. SIADH has been associated with many clinical states or syndromes, and the hypothalamic-neurohypophyseal system regulates the feedback control system for ADH secretion. We report the case of a 63-year-old man with NMO, whose initial manifestation was hyponatremia caused by SIADH. Retrospective analysis revealed that the serum anti-AQP4 antibody was positive, and an MRI scan showed a unilateral lesion in the hypothalamus. SIADH recovered completely with regression of the hypothalamic lesion. As such, NMO should even be considered in patients who develop SIADH and have no optic nerve or spinal cord lesions but have MRI-documented hypothalamic lesions.

  11. Glio-vascular modifications caused by Aquaporin-4 deletion in the mouse retina.

    Science.gov (United States)

    Nicchia, Grazia Paola; Pisani, Francesco; Simone, Laura; Cibelli, Antonio; Mola, Maria Grazia; Dal Monte, Massimo; Frigeri, Antonio; Bagnoli, Paola; Svelto, Maria

    2016-05-01

    Aquaporin-4 (AQP4) is the Central Nervous System water channel highly expressed at the perivascular glial domain. In the retina, two types of AQP4 expressing glial cells take part in the blood-retinal barrier (BRB), astrocytes and Müller cells. The aim of the present study is to investigate the effect of AQP4 deletion on the retinal vasculature by looking at typical pathological hallmark such as BRB dysfunction and gliotic condition. AQP4 dependent BRB properties were evaluated by measuring the number of extravasations in WT and AQP4 KO retinas by Evans blue injection assay. AQP4 deletion did not affect the retinal vasculature, as assessed by Isolectin B4 staining, but caused BRB impairment to the deep plexus capillaries while the superficial and intermediate capillaries were not compromised. To investigate for gliotic responses caused by AQP4 deletion, Müller cells and astrocytes were analysed by immunofluorescence and western blot, using the Müller cell marker Glutamine Synthetase (GS) and the astrocyte marker GFAP. While GS expression was not altered in AQP4 KO retinas, a strong GFAP upregulation was found at the level of AQP4 KO astrocytes at the superficial plexus and not at Müller cells at the intermediate and deep plexi. These data, together with the upregulation of inflammatory markers (TNF-α, IL-6, IL-1β and ICAM-1) in AQP4 KO retinas indicated AQP4 deletion as responsible for a gliotic phenotype. Interestingly, no GFAP altered expression was found in AQP4 siRNA treated astrocyte primary cultures. All together these results indicate that AQP4 deletion is directly responsible for BRB dysfunction and gliotic condition in the mouse retina. The selective activation of glial cells at the primary plexus suggests that different regulatory elements control the reaction of astrocytes and Müller cells. Finally, GFAP upregulation is strictly linked to gliovascular crosstalk, as it is absent in astrocytes in culture. This study is useful to understand the role

  12. Metal ion toxins and brain aquaporin-4 expression: an overview

    OpenAIRE

    Adriana eXimenes-Da-Silva

    2016-01-01

    Metal ions such as iron, zinc, and manganese are essential to metabolic functions, protein synthesis, neurotransmission, and antioxidant neuroprotective mechanisms. Conversely, non-essential metals such as mercury and lead are sources of human intoxication due to occupational activities or environmental contamination. Essential or non-essential metal accumulation in the central nervous system (CNS) results in changes in blood-brain barrier (BBB) permeability, as well as triggering microglia a...

  13. Metal Ion Toxins and Brain Aquaporin-4 Expression: An Overview

    OpenAIRE

    Ximenes-da-Silva, Adriana

    2016-01-01

    Metal ions such as iron, zinc, and manganese are essential to metabolic functions, protein synthesis, neurotransmission, and antioxidant neuroprotective mechanisms. Conversely, non-essential metals such as mercury and lead are sources of human intoxication due to occupational activities or environmental contamination. Essential or non-essential metal accumulation in the central nervous system (CNS) results in changes in blood-brain barrier (BBB) permeability, as well as triggering microglia a...

  14. Correlation of aquaporin-4 expression to blood-brain barrier permeability in rats with focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Pengcheng Xu; Haorong Feng; Jinbu Xu; Yongping Wu

    2008-01-01

    BACKGROUND: Ischemic cerebrovascular disease causes injury to the blood-brain barrier. The occurrence of brain edema is associated with aquaporin expression following cerebral ischemia/reperfusion. OBJECTIVE: To analyze the correlation of aquaporin-4 expression to brain edema and blood-brain barrier permeability in brain tissues of rat models of ischemia/reperfusion. DESIGN, TIME AND SETTING: The randomized control experiment was performed at the Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, China from December 2006 to October 2007. MATERIALS: A total of 112 adult, male, Sprague-Dawley rats, weighing 220-250 g, were used to establish rat models of middle cerebral artery occlusion and reperfusion by the suture method. Rabbit anti-aquaporin-4 (Santa Cruz, USA) and Evans blue (Sigma, USA) were used to analyze the tissue. METHODS: The rats were randomized into sham-operated (n = 16) and ischemia/reperfusion (n = 96) groups. There were 6 time points in the ischemia/reperfusion group, comprising 4, 6, 12, 24, 48, and 72 hours after reperfusion, with 16 rats for each time point. Rat models in the sham-operated group at 4 hours after surgery and rat models in the ischemia/reperfusion group at different time points were equally and randomly assigned into 4 different subgroups. MAIN OUTCOME MEASURES: Brain water content on the ischemic side and the control side was measured using the dry-wet weight method. Blood-brain barrier function was determined by Evans Blue. Aquaporin-4 expression surrounding the ischemic focus, as well as the correlation of aquaporin-4 expression with brain water content and Evans blue staining, were measured using immunohistochemistry and Western blot analysis. RESULTS: Brain water content on the ischemic side significantly increased at 12 hours after reperfusion, reached a peak at 48 hours, and was still high at 72 hours. Brain water content was greater on the ischemic hemispheres, compared with the control hemispheres

  15. Binding Affinity and Specificity of Neuromyelitis Optica Autoantibodies to Aquaporin-4 M1/M23 Isoforms and Orthogonal Arrays*

    OpenAIRE

    Crane, Jonathan M.; Lam, Chiwah; Rossi, Andrea; Gupta, Tripta; Bennett, Jeffrey L.; Verkman, A S

    2011-01-01

    Autoantibodies against astrocyte water channel aquaporin-4 (AQP4) are highly specific for the neuroinflammatory disease neuromyelitis optica (NMO). We measured the binding of NMO autoantibodies to AQP4 in human astrocyte-derived U87MG cells expressing M1 and/or M23 AQP4, or M23 mutants that do not form orthogonal array of particles (OAPs). Binding affinity was quantified by two-color fluorescence ratio imaging of cells stained with NMO serum or a recombinant monoclonal NMO autoantibody (NMO-r...

  16. Preventive administration of cromakalim reduces aquaporin-4 expression and blood-brain barrier permeability in a rat model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Shilei Wang; Yanting Wang; Yan Jiang; Qingxian Chang; Peng Wang; Shiduan Wang

    2011-01-01

    Cromakalim, an adenosine triphosphate-sensitive potassium channel opener, exhibits protective effects on cerebral ischemia/reperfusion injury. However, there is controversy as to whether this effect is associated with aquaporin-4 and blood-brain barrier permeability. Immunohistochemistry results show that preventive administration of cromakalim decreased aquaporin-4 and IgG protein expression in rats with ischemia/reperfusion injury; it also reduced blood-brain barrier permeability, and alleviated brain edema, ultimately providing neuroprotection.

  17. 补阳还五汤对脑出血大鼠脑组织水通道蛋白4表达及血-脑脊液屏障通透性的影响研究%Effects of Buyanghuanwu Decoction on Aquaporin 4 Expression and the Permeability of the Blood Brain Barrier in Cerebral Hemorrhage Rats

    Institute of Scientific and Technical Information of China (English)

    刘绍晨; 吴晓光; 杨岚; 李义学; 仇志富

    2016-01-01

    Objective To explore the effects of Buyanghuanwu decoction on aquaporin 4(AQP4)expression and the permeability of the blood brain barrier in cerebral hemorrhage rats. Methods From March 2014 to November 2015,SPF level adult male SD rats were randomly divided into sham operation group,model group,Buyanghuanwu decoction low,medium and high dose groups, 24 in each group. Model group and Buyanghuanwu decoction groups prepared models of cerebral hemorrhage. Since two days after modeling, Buyanghuanwu decoction low, medium, and high dose groups were given Buyanghuanwu decoction by gastric perfusion,the dose was 13. 2 g·kg - 1 ·d - 1 ,26. 5 g·kg - 1 ·d - 1 and 53. 0 g·kg - 1 ·d - 1 respectively,continuously for 14 days,and sham operation group and model group were given the equal volume of the corresponding 0. 9% sodium chloride solution. The expression of phosphatidylinositol 3 kinase( PI3K) and protein kinase B (AKT ) was detected by immunohistochemistry. The expression of AQP4 was detected by immunofluorescence labeling method. Content of water in brain was detected by wet and dry weight method,and formamide method was used to detect the blood- brain barrier permeability. Results Sham operation group,model group,Buyanghuanwu decoction low,medium and high dose groups were significantly different in the expression of PI3K and AKT(P ﹤ 0. 05);Buyanghuanwu decoction low,medium and high dose groups were higher than model group in the expression of PI3K;Buyanghuanwu decoction medium and high dose groups were higher than model group in the expression of AKT( P ﹤ 0. 05). The 5 groups were significantly different in the expression of AQP4(F = 95. 79,P ﹤ 0. 001);Buyanghuanwu decoction low,medium and high dose groups were higher than model group in the expression of AQP4 ( P ﹤ 0. 05) . The 5 groups were significantly different in brain water content( F= 16. 21,P ﹤ 0. 001);Buyanghuanwu decoction high dose group was lower than model group in brain water content( P

  18. Detection of aquaporins-4:methods comparison and clinical significance for the diagnosis of neuromyelitis optica%水通道蛋白4抗体检测的方法学比较及其临床意义

    Institute of Scientific and Technical Information of China (English)

    龙友明; 胡学强; 王俊峰; 陆正齐; 王玉鸽; 杨渝; 李盈

    2010-01-01

    目的 比较经典分析法和水通道蛋白4(AQP4)抗体分析法对AQP4抗体检测率的异同,并探讨该抗体对区分中国视神经脊髓炎(NMO)和多发性硬化(MS)患者的诊断准确度.方法 选择44例NMO和46例MS患者的血清,采用经典分析法检测血清中的NMO-IgG(AQP4),AQP4抗体分析法检测血清中AQP4抗体.结果 90份血清中,两种方法检测结果均为阳性的36份,两种方法检测结果均为阴性的45份,经典分析法阳性但AQP4抗体分析法阴性血清4份,AQP4抗体分析法阳性但经典分析法阴性血清5份,2种方法的阳性率、阴性率差异无统计学意义(P=1.000).2种方法一致性检验Kappa=0.798,P=0.000.经典分析法检测NMO患者NMO-IgG的灵敏度为77.3%,阳性预测值85.0%,特异度87.0%,阴性预测值87.0%,诊断正确率为82.2%,Youden指数74.3%.AQP4抗体分析法检测NMO患者AQP4抗体的灵敏度为88.6%,阳性预测值95.1%,特异度95.7%,阴性预测值89.8%,诊断正确率为92.2%,Youden指数84.3%.结论 两种AQP4抗体检测方法对区分MS与NMO都具有高灵敏度与特异度,但是抗AQP4抗体分析法对NMO诊断具有更高的诊断准确性,值得推广.%Objective To compare the efficiency of original neuromyelitis optica(NMO)-IgG assay of detecting NMO-IgG with a new anti-aquaporin-4(AQP4)assay of detecting AQP4,and to explore the accuracy of the method in the diagnosis of NMO and multiple sclerosis(MS).Methods The sera were obtained from 44 patients with NMO and 46 patients with MS and were tested by both NMO-IgG and antiAOP4 assays.NMO-IgG was identified by original NMO-IgG assay with a substrate from mouse brain.AntiAQIP4 was detected by anti-AQP4 antibody assay.The results from the two assays were statistically analyzed to compare accuracy and specificity of the methods.Results The results of the two assays were concordant in 45 testing negative cases and 36 positive cases(Kappa=0.798.P=0.000).The McNemar test showed that the positive rate of the

  19. TRPV4 and AQP4 Channels Synergistically Regulate Cell Volume and Calcium Homeostasis in Retinal Müller Glia

    DEFF Research Database (Denmark)

    Jo, Andrew O; Ryskamp, Daniel A; Phuong, Tam T T;

    2015-01-01

    facilitates the time course and amplitude of hypotonicity-induced swelling and regulatory volume decrease. We confirm the crucial facets of the signaling mechanism in heterologously expressing oocytes. These results identify the molecular mechanism that contributes to dynamic regulation of glial volume but...... Ca(2+) entry through TRPV4 channels reciprocally modulates volume regulation, swelling, and Aqp4 gene expression. Therefore, TRPV4-AQP4 interactions constitute a molecular system that fine-tunes astroglial volume regulation by integrating osmosensing, calcium signaling, and water transport and, when...... complex set of mechanisms involving reciprocal interactions at the level of glial gene expression, calcium homeostasis, swelling, and volume regulation. Specifically, water influx through AQP4 drives calcium influx via TRPV4 in the glial end foot, which regulates expression of Aqp4 and Kir4.1 genes and...

  20. Change of apuaporin4 in rats during brain edema induced by lipid polysaccharide%水通道蛋白4在脂多糖致大鼠感染性脑水肿模型中的表达变化

    Institute of Scientific and Technical Information of China (English)

    胡佳; 高进; 陈萍

    2011-01-01

    Objective:To observe the expression of aquaporin - 4 (AQP4) in rats with brain edema induced by lipid polysaccharide (LPS) as well as to expl6re the role of AQP4 in the formation and development of brain edema. Methods Eighty four SD male rats were randomly divided into 3 groups: control group( group C,n = 12), saline group (group S, n = 12), LPS group (group L, n = 60). Group L was devided into 5 subgroups according to different time points after injecting LPS: 6h, 12h, 24h,48h,72h ( each subgroup, n = 12). Cerebral edema was induced by carotid injection with LPS ( 150μg/150μL). Dry - wet weight, evan blue,RT- PCR and immunohistochemistry methods were used respectively to measure the brain tissue water content, the integrity of BBB , the expression of AQP4 mRNA and AQP4 protein. Results: Compared with group C and group S, the brain tissue water content, EB content, AQP4 mRNA andprotein were significantly increased (P<0.05) in group L,except subgroup 72h. They were increased at 6h after LPS injection, with a peak at 24h. No significant difference was found between group C and group S(P> 0.05). Conclusion: The results suggest that the expression of AQP4 is up regulated in brain edema induced by LPS, and it has positive relationship with the integrity of BBB and the brain tissue water content. It shows AQP4 may participat in the formation and development of infections cerebral edema.%目的:观察脂多糖(LPS)致大鼠感染性脑水肿后水通道蛋白4的表达情况.探讨其在脑水肿形成发展中的作用.方法:84只雄性SD大鼠,随机分为3组:空白对照组(C组,n=12):生理盐水对照组(S组,n=12):水肿组(L组,n=60).水肿组又按注射脂多精后6h、12h、24h、48h、72h分为5个亚组(n=12).向颈内动脉注射脂多糖LPSl50μg(0.15mL)建立大鼠感染性脑水肿模型.采用干湿重法、甲酰胺法、PT-PCR和免疫组化法分别测定脑组织含水量、血脑屏障通透性、AQP4mRNA和AQP4蛋白表达.结果:

  1. Binding affinity and specificity of neuromyelitis optica autoantibodies to aquaporin-4 M1/M23 isoforms and orthogonal arrays.

    Science.gov (United States)

    Crane, Jonathan M; Lam, Chiwah; Rossi, Andrea; Gupta, Tripta; Bennett, Jeffrey L; Verkman, A S

    2011-05-01

    Autoantibodies against astrocyte water channel aquaporin-4 (AQP4) are highly specific for the neuroinflammatory disease neuromyelitis optica (NMO). We measured the binding of NMO autoantibodies to AQP4 in human astrocyte-derived U87MG cells expressing M1 and/or M23 AQP4, or M23 mutants that do not form orthogonal array of particles (OAPs). Binding affinity was quantified by two-color fluorescence ratio imaging of cells stained with NMO serum or a recombinant monoclonal NMO autoantibody (NMO-rAb), together with a C terminus anti-AQP4 antibody. NMO-rAb titrations showed binding with dissociation constants down to 44 ± 7 nm. Different NMO-rAbs and NMO patient sera showed a wide variation in NMO-IgG binding to M1 versus M23 AQP4. Differences in binding affinity rather than stoichiometry accounted for M1 versus M23 binding specificity, with consistently greater affinity of NMO-IgG binding to M23 than M1 AQP4. Binding and OAP measurements in cells expressing different M1:M23 ratios or AQP4 mutants indicated that the differential binding of NMO-IgG to M1 versus M23 was due to OAP assembly rather than to differences in the M1 versus M23 N termini. Purified Fab fragments of NMO-IgG showed similar patterns of AQP4 isoform binding, indicating that structural changes in the AQP4 epitope upon array assembly, and not bivalent cross-linking of whole IgG, result in the greater binding affinity to OAPs. Our study establishes a quantitative assay of NMO-IgG binding to AQP4 and indicates remarkable, OAP-dependent heterogeneity in NMO autoantibody binding specificity. PMID:21454592

  2. Altered aquaporin expression in glaucoma eyes

    DEFF Research Database (Denmark)

    Tran, Thuy Linh; Bek, Toke; la Cour, Morten;

    2014-01-01

    , AQP7 and AQP9 in human glaucoma eyes compared with normal eyes. Nine glaucoma eyes were examined. Of these, three eyes were diagnosed with primary open angle glaucoma; three eyes had neovascular glaucoma; and three eyes had chronic angle-closure glaucoma. Six eyes with normal intraocular pressure and...... intensity (p = 0.037). No difference in AQP1, AQP4 and AQP9 expression was found in the optic nerve fibres. This study is the first investigating AQPs in human glaucoma eyes. We found a reduced expression of AQP9 in the retinal ganglion cells of glaucoma eyes. Glaucoma also induced increased AQP7 expression......Aquaporins (AQP) are channels in the cell membrane that mainly facilitate a passive transport of water. In the eye, AQPs are expressed in the ciliary body and retina and may contribute to the pathogenesis of glaucoma and optic neuropathy. We investigated the expression of AQP1, AQP3, AQP4, AQP5...

  3. 水通道蛋白4示踪系统的构建及评价%Construction and evaluation of green fluorescent protein labeled aquaporin 4 tracing system

    Institute of Scientific and Technical Information of China (English)

    袁志华; 姜久昆; 潘建; 祝建勇; 陆远强

    2011-01-01

    目的 构建绿色荧光蛋白(GFP)标识的水通道蛋白4(AQP4)示踪系统,建立表达AQP4的大鼠星形胶质细胞水通透性的评价系统. 方法 利用基因重组技术,构建pEGFP-C1 -AQP4-M23表达质粒,并转染CTX-TNA2星形胶质细胞,利用激光扫描共聚焦显微镜(LSCM)成像技术分析GFP标记的AQP4-M23在细胞上的分布,动态观察钙黄绿素荧光强度随时间的变化,评价AQP4-M23对细胞膜水通透性的影响.结果 正确获取AQP4-M23全长序列,利用基因重组技术连接pEGFP-C1质粒和AQP4-M23序列,酶切证实成功构建pEGFP-C1-AQP4-M23质粒.LSCM扫描显示GFP标记的AQP4-M23融合蛋白在细胞膜上均匀分布表达,胞浆内仅痕量表达;表达AQP4-M23的CTX-TNA2细胞对水的通透性明显增加(P<0.01). 结论 成功构建了GFP标识的AQP4示踪系统,建立了表达AQP4的大鼠星形胶质细胞水通透性的评价系统,AQP4可使星形胶质细胞对水的通透性明显增加.%Objective To construct the green fluorescent protein (GFP) labeled aquaporin 4 (AQP4) tracing system,and establish the water permeability evaluation system for rat astrocytes expressing AQP4.Methods Using the gene recombination technique,the AQP4-M23 sequences were acquired by reverse transcription polymerase chain reaction and authenticated by gel electrophoresis to construct the pEGFP-C1-AQP4-M23.Then the plasmids were transfected transiently into CTX-TNA2 astrocytes which were cultured 24 h to express protein.The laser scanning confocal microscope imaging technology was employed to record fluorescence images of GFP and variation of calcein fluorescence intensity.Results The target gene (AQP4-M23) was acquired,and the restriction enzyme cutting sites of Hind Ⅲ and Xba Ⅰ were also correctly introduced.The plasmids pEGFP-C1 and the sequence AQP4-M23 were ligated GFP which located at the amino terminal of AQP4-M23 did not affect the location of AQP4-M23 on cell membrane.Compared with the non-AQP4-M23

  4. Treadmill exercise ameliorates ischemia-induced brain edema while suppressing Na⁺/H⁺ exchanger 1 expression.

    Science.gov (United States)

    Nishioka, Ryutaro; Sugimoto, Kana; Aono, Hitomi; Mise, Ayano; Choudhury, Mohammed E; Miyanishi, Kazuya; Islam, Afsana; Fujita, Takahiro; Takeda, Haruna; Takahashi, Hisaaki; Yano, Hajime; Tanaka, Junya

    2016-03-01

    Exercise may be one of the most effective and sound therapies for stroke; however, the mechanisms underlying the curative effects remain unclear. In this study, the effects of forced treadmill exercise with electric shock on ischemic brain edema were investigated. Wistar rats were subjected to transient (90 min) middle cerebral artery occlusion (tMCAO). Eighty nine rats with substantially large ischemic lesions were evaluated using magnetic resonance imaging (MRI) and were randomly assigned to exercise and non-exercise groups. The rats were forced to run at 4-6m/s for 10 min/day on days 2, 3 and 4. Brain edema was measured on day 5 by MRI, histochemical staining of brain sections and tissue water content determination (n=7, each experiment). Motor function in some rats was examined on day 30 (n=6). Exercise reduced brain edema (Pexercise. Exercise prevented the ischemia-induced expression of mRNA encoding aquaporin 4 (AQP4) and Na(+)/H(+) exchangers (NHEs) (n=5 or 7, Prat brains and also in mixed glial cultures. Corticosterone at ~10nM reduced NHE1 and AQP4 expression in mixed glial and pure microglial cultures. Dexamethasone and aldosterone at 10nM did not significantly alter NHE1 and AQP4 expression. Exposure to a NHE inhibitor caused shrinkage of microglial cells. These results suggest that the stressful short-period and slow-paced treadmill exercise suppressed NHE1 and AQP4 expression resulting in the amelioration of brain edema at least partly via the moderate increase in plasma corticosterone levels. PMID:26724742

  5. Expression and function of aquaporins in peripheral nervous system

    OpenAIRE

    Ma, Tong-hui; Gao, Hong-Wen; Fang, Xue-Dong; Yang, Hong

    2011-01-01

    The expression and role of the aquaporin (AQP) family water channels in the peripheral nervous system was less investigated. Since 2004, however, significant progress has been made in the immunolocalization, regulation and function of AQPs in the peripheral nervous system. These studies showed selective localization of three AQPs (AQP1, AQP2, and AQP4) in dorsal root ganglion neurons, enteric neurons and glial cells, periodontal Ruffini endings, trigeminal ganglion neurons and vomeronasal sen...

  6. Inhibition of chemokine-like factor 1 improves blood-brain barrier dysfunction in rats following focal cerebral ischemia.

    Science.gov (United States)

    Kong, Ling-Lei; Wang, Zhi-Yuan; Hu, Jin-Feng; Yuan, Yu-He; Li, Hua; Chen, Nai-Hong

    2016-08-01

    Disruption of blood-brain barrier (BBB) and subsequent edema are major contributors to the pathogenesis of ischemic stroke, and the current clinical therapy remains unsatisfied. Chemokine-like factor 1 (CKLF1), as a novel C-C chemokine, plays important roles in immune response. The expression of CKLF1 increased after focal cerebral ischemia and inhibition of CKLF1 activity showed neuroprotective effect by alleviating infiltration of neutrophil and neuron apoptosis in cerebral ischemia. However, few studies have focused on the role of CKLF1 on BBB integrity. The objective of present study was to investigate the role of CKLF1 on BBB integrity by applying anti-CKLF1 antibodies in rat focal cerebral ischemia and reperfusion model. Brain water content, Evans blue leakage and the expression of aquaporin-4 (AQP-4), matrix metalloproteinase-9 (MMP-9), Zonula Occludens-1 (ZO-1) and Occludin were measured. After treatment with anti-CKLF1 antibody, brain water content and Evans blue leakage in ipsilateral hemisphere were decreased in a dose-dependent manner at 24h after reperfusion, but not changed in contralateral hemisphere. Anti-CKLF1 antibody reduced the expression of AQP-4 and MMP-9, and upregulated the expression of ZO-1 and Occludin. These results suggest that CKLF1 is involved in BBB disruption after reperfusion. Inhibition of CKLF1 protects against cerebral ischemia by maintaining BBB integrity, possibly via inhibiting the expression of AQP-4 and MMP-9, and increasing the expression of tight junction protein. PMID:27283776

  7. Evaluation of Clinical Interest of Anti-Aquaporin-4 Autoantibody Followup in Neuromyelitis Optica

    Directory of Open Access Journals (Sweden)

    Jean-Baptiste Chanson

    2013-01-01

    Full Text Available Neuromyelitis optica (NMO is an autoimmune disease in which a specific biomarker named NMO-IgG and directed against aquaporin-4 (AQP4 has been found. A correlation between disease activity and anti-AQP4 antibody (Ab serum concentration or complement-mediated cytotoxicity has been reported, but the usefulness of longitudinal evaluation of these parameters remains to be evaluated in actual clinical practice. Thirty serum samples from 10 NMO patients positive for NMO-IgG were collected from 2006 to 2011. Anti-AQP4 Ab serum concentration and complement-mediated cytotoxicity were measured by flow cytometry using two quantitative cell-based assays (CBA and compared with clinical parameters. We found a strong correlation between serum anti-AQP4 Ab concentration and complement-mediated cytotoxicity (P<0.0001. Nevertheless, neither relapse nor worsening of impairment level was closely associated with a significant increase in serum Ab concentration or cytotoxicity. These results suggest that complement-mediated serum cytotoxicity assessment does not provide extra insight compared to anti-AQP4 Ab serum concentration. Furthermore, none of these parameters appears closely related to disease activity and/or severity. Therefore, in clinical practice, serum anti-AQP4 reactivity seems not helpful as a predictive biomarker in the followup of NMO patients as a means of predicting the onset of a relapse and adapting the treatment accordingly.

  8. Astrocyte Aquaporin Dynamics in Health and Disease.

    Science.gov (United States)

    Potokar, Maja; Jorgačevski, Jernej; Zorec, Robert

    2016-01-01

    The family of aquaporins (AQPs), membrane water channels, consists of diverse types of proteins that are mainly permeable to water; some are also permeable to small solutes, such as glycerol and urea. They have been identified in a wide range of organisms, from microbes to vertebrates and plants, and are expressed in various tissues. Here, we focus on AQP types and their isoforms in astrocytes, a major glial cell type in the central nervous system (CNS). Astrocytes have anatomical contact with the microvasculature, pia, and neurons. Of the many roles that astrocytes have in the CNS, they are key in maintaining water homeostasis. The processes involved in this regulation have been investigated intensively, in particular regulation of the permeability and expression patterns of different AQP types in astrocytes. Three aquaporin types have been described in astrocytes: aquaporins AQP1 and AQP4 and aquaglyceroporin AQP9. The aim here is to review their isoforms, subcellular localization, permeability regulation, and expression patterns in the CNS. In the human CNS, AQP4 is expressed in normal physiological and pathological conditions, but astrocytic expression of AQP1 and AQP9 is mainly associated with a pathological state. PMID:27420057

  9. 骨髓间充质干细胞联合超短波对大鼠脊髓损伤后早期AQP-4和GAP-43的影响%Effects of bone marrow stromal cells transplantation combined with ultrashort wave therapy on the expression of AQP-4 and GAP-43 after spinal cord injury in rats

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    目的:探讨骨髓间充质干细胞(bone marrow stromal cells,BMSCs)联合超短波(ultrashort wave,USW)治疗对大鼠脊髓损伤(spinal cord injury,SCI)后功能恢复、水通道蛋白4(aquaporin-4,AQP-4)和生长相关蛋白43(growth associated protein 43,GAP-43)表达的影响.方法:30只雌性SD大鼠,随机分为5组:sham组、control组、USW组、BMSCs组、USW+BMSCs联合治疗组,采用改良Allen's法制作大鼠SCI模型,术后1d、1周、2周、3周、4周用BBB评分法评价后肢运动功能的恢复情况.术后4周取材行AQP-4和GAP-43的免疫组化染色,并行阳性细胞计数,进行比较分析.结果:术后4周BBB评分各组比较有显著性意义,USW组、BMSCs组、USW+BMSCs组与control组比较P<0.001、P>0.05、P<0.001.USW组、BMSCs组、USW+BMSCs组AQP-4表达水平明显低于control组,有显著性意义(P<0.001、P<0.05、P<0.001).GAP-43的表达上,BMSCs组、USW+BMSCs组明显多于control组及USW组,分别比较均有显著性意义(P<0.001).结论:单纯USW治疗即可明显改善SCI后神经功能;单纯USW治疗及BMSCs移植治疗均可减轻水肿,以USW作用最为显著;而在促进轴突再生方面,BMSCs组意义更为明显.二者联合治疗在促进功能恢复上并未显现出协同作用,但是在减轻水肿和促进轴突生长方面有协同作用.

  10. Absence of aquaporin-4 in skeletal muscle alters proteins involved in bioenergetic pathways and calcium handling.

    Directory of Open Access Journals (Sweden)

    Davide Basco

    Full Text Available Aquaporin-4 (AQP4 is a water channel expressed at the sarcolemma of fast-twitch skeletal muscle fibers, whose expression is altered in several forms of muscular dystrophies. However, little is known concerning the physiological role of AQP4 in skeletal muscle and its functional and structural interaction with skeletal muscle proteome. Using AQP4-null mice, we analyzed the effect of the absence of AQP4 on the morphology and protein composition of sarcolemma as well as on the whole skeletal muscle proteome. Immunofluorescence analysis showed that the absence of AQP4 did not perturb the expression and cellular localization of the dystrophin-glycoprotein complex proteins, aside from those belonging to the extracellular matrix, and no alteration was found in sarcolemma integrity by dye extravasation assay. With the use of a 2DE-approach (BN/SDS-PAGE, protein maps revealed that in quadriceps, out of 300 Coomassie-blue detected and matched spots, 19 proteins exhibited changed expression in AQP4(-/- compared to WT mice. In particular, comparison of the protein profiles revealed 12 up- and 7 down-regulated protein spots in AQP4-/- muscle. Protein identification by MS revealed that the perturbed expression pattern belongs to proteins involved in energy metabolism (i.e. GAPDH, creatine kinase, as well as in Ca(2+ handling (i.e. parvalbumin, SERCA1. Western blot analysis, performed on some significantly changed proteins, validated the 2D results. Together these findings suggest AQP4 as a novel determinant in the regulation of skeletal muscle metabolism and better define the role of this water channel in skeletal muscle physiology.

  11. Identification and expression analysis of aquaporins in the potato psyllid, Bactericera cockerelli.

    Directory of Open Access Journals (Sweden)

    Freddy Ibanez

    Full Text Available Aquaporin (AQPs proteins transport water and uncharged low molecular-weight solutes across biological membranes. Six to 8 AQP genes have been identified in many insect species, but presently only three aquaporins have been characterized in phloem feeding insects. The objective of this study was to identify candidate AQPs in the potato psyllid, Bactericera cockerelli. Herein, we identified four candidate aquaporin cDNAs in B. cockerelli transcriptome. Phylogenetic analysis showed that candidate BcAQP2-like had high similarity to PRIP aquaporins; while candidates BcAQP4-like, BcAQP5-like and BcAQP9-like clustered within clade B. In particular, candidates BcAQP4-like and BcAQP5-like clustered with functionally validated insect aquaglyceroporin proteins. Expression analyses using RT-qPCR showed that all candidates were expressed in all life stages and tissues. Candidates BcAQP4-like and BcAQP5-like were highly expressed in bacteriocytes, while BcAQP9-like appeared to be expressed at high levels in whole body but not in the assayed tissues. This study is the first global attempt to identify putative aquaporins in a phloem feeding insect.

  12. Vasopressin-dependent short-term regulation of aquaporin 4 expressed in Xenopus oocytes

    DEFF Research Database (Denmark)

    Moeller, H B; Fenton, R A; Zeuthen, T;

    2009-01-01

    following pathologies such as brain injuries, brain tumours, and cerebral ischemia. As vasopressin and its G-protein-coupled receptor (V1(a)R) have been shown to affect the outcome of brain edema, we have investigated the regulatory interaction between AQP4 and V1(a)R by heterologous expression in Xenopus...... laevis oocytes. The water permeability of AQP4/V1(a)R-expressing oocytes was reduced in a vasopressin-dependent manner, as a result of V1(a)R-dependent internalization of AQP4. Vasopressin-dependent internalization was not observed in AQP9/V1(a)R-expressing oocytes. The regulatory interaction between AQP......4 and V1(a)R involves protein kinase C (PKC) activation and is reduced upon mutation of Ser(180) on AQP4 to an alanine. Thus, the present study demonstrates at the molecular level a functional link between the vasopressin receptor V1(a)R and AQP4. This functional interaction between AQP4 and V1(a...

  13. 抗水通道蛋白-4抗体应用于中枢神经系统脱髓鞘疾病的鉴别诊断价值%Clinical value of application of AQP-4 antibody in differentiation diagnosis of central nervous system demyelination dis-eases

    Institute of Scientific and Technical Information of China (English)

    连淑芬

    2015-01-01

    Objective To explore the clinical significance of the application of serum aquaporin-4(AQP-4)an-tibody in the diagnosis of multiple sclerosis and neuromyelitis opica(NMO).Methods 74 cases of multiple sclerosis and NMO in this hospital from March 2013 to October 2014 were selected and their clinical data were retrospectively analyzed.The serum AQP-4 antibody was detected.Results The AQP-4 antibody positive rates of various types of NMO were 5 1.89% for optic neuritis(ON),68.42% for long segment transverse myelitis (LETM),57.14% for op-ticospinal multiple sclerosis (OSMS)and 81.25% for NMO;but the AQP-4 antibody detection in the conventional multiple sclerosis(CMS)was negative.(2 )In the patients of NMO disease spectrum,the spinal cord was involved more than 3 vertebral segments;while in multiple sclerosis,the involved spinal cord was less than 3 segments.(3 ) NMO was mostly acute or subacute onset,more common in middle-aged women,the mean age at the onset was (42.1±13.9)years,the difference between NMO and CMS had no statistical difference(P > 0.05 ).Conclusion AQP-4 antibody can be used as an important index of the differentiation diagnosis between NMO and multiple sclero-sis.%目的:探讨血清抗水通道蛋白-4(AQP-4)抗体应用于多发性硬化和视神经脊髓炎患者疾病诊断的临床意义。方法选择2013年3月至2014年10月该院收治的74例多发性硬化以及视神经脊髓炎患者,回顾性分析其临床资料,对血清中 AQP-4抗体水平进行检查。结果视神经脊髓炎疾病患者各类型的阳性率分别为视神经炎(ON)51.89%、长节段横贯性脊髓炎(LETM)68.42%、视神经脊髓型多发性硬化(OSMS)57.14%、视神经脊髓炎(NMO)81.25%;而传统型多发性硬化(CMS)患者的 AQP-4抗体检测为阴性。视神经脊髓炎疾病谱的患者脊髓受累均大于3个椎体节段;多发性硬化脊髓受累均小于3个节段。视神经脊髓炎多为急性或亚急性起病,多见于中

  14. Pain in patients with transverse myelitis and its relationship to aquaporin 4 antibody status.

    Science.gov (United States)

    Kong, Yazhuo; Okoruwa, Helen; Revis, Jon; Tackley, George; Leite, Maria Isabel; Lee, Michael; Tracey, Irene; Palace, Jacqueline

    2016-09-15

    Pain in transverse myelitis has been poorly studied. The aim of the study was to investigate the relationship between transverse myelitis related pain and disability, quality of life, anxiety and depression, cognitive-affective states in neuromyelitis optica (NMO) patients and aquaporin4 antibody status (AQP4-Ab +ve as positive and AQP4-Ab -ve as negative). Transverse myelitis patients (44 in total; 29 AQP4-Ab +ve and 15 AQP4-Ab -ve) completed questionnaires including Pain Severity Index (PSI), Pain Catastrophising Scale (PCS), Hospital Anxiety and Depression Scale (HADS), Short Form-36 quality of life (SF-36 QOL). Clinical details such as disability, gender, age and spinal cord lesion type (short or long lesion) were noted. Correlation and multiple linear regression tests were performed using these clinical scores. Pain was found to be correlated strongly with quality of life in both groups but only correlated with disability in the AQP4-Ab +ve group. PCS, HADS and EDMUS were found to be highly correlated with pain severity using partial correlation, however, a stronger relationship between pain severity and PCS was found in the AQP4-Ab -ve group. Multiple regression analysis showed that pain severity was the most important factor for quality of life but not disability or anxiety and depression symptoms in the whole patient group. We confirm that pain is an important symptom of transverse myelitis and has more influence on quality of life than disability despite health services being predominantly focused on the latter. There may be different factors associated with pain between AQP4-Ab +ve and -ve patients. PMID:27538606

  15. Protective effects of different dose of ulinastatin pretreatment on traumatic brain edema in mice%不同剂量乌司他丁预处理对小鼠创伤性脑水肿的影响

    Institute of Scientific and Technical Information of China (English)

    饶维; 张磊; 曹宝萍; 马选鹏; 苏宁; 王凯; 张强; 费舟; 李兵

    2012-01-01

    Objective To investigate the potential therapeutic effect and the related mechanism of ulinaslatin (UTI) on traumatic brain edema in mice. Methods Thirty-eight BALB/c mice were randomly divided into two groups: isotonic Na chloride control group (control group) and UTI pretreatment group (UTI group). The wet-dry weighing method was performed to measure the brain water content of mice. The expression of aquaporin4 (AQP4) was detected by Western blot. Results Compared with control group, UTI significantly inhibited (he neurological dysfunction of mice in a concentration-dependent manner and reduced brain water content. It is suggested that UTI could down-regulate the expression of AQP4 (P<0. 05). Conclusion Pretreatment of UTI can effectively protect traumatic brain edema, which may be associated with the regulation of AQP4 expression.%目的 探讨乌司他丁(UTI)预处理对小鼠创伤性脑水肿潜在的治疗作用及其机制.方法 BALB/c小鼠38只,随机分为生理盐水对照组(control组)和乌司他丁预处理组(UTI组).采用测干湿重法检测不同剂量UTI预处理对小鼠脑组织含水量的影响和Western -blot检测脑组织中水通道蛋白4(AQP4)蛋白表达情况.结果 与生理盐水对照组比较,UTI能明显减轻神经功能障碍,干湿重法检测结果显示,随着UTI剂量的增大小鼠脑组织含水量明显降低,Western-blot结果提示UTI下调AQP4蛋白的表达,不同组间差异有统计学意义(P<0.05).结论 乌司他丁预处理能减轻创伤性脑水肿,具有显著的神经保护作用,可能是通过调控AQP4而减轻脑组织水肿.

  16. Highly encephalitogenic aquaporin 4-specific T cells and NMO-IgG jointly orchestrate lesion location and tissue damage in the CNS

    DEFF Research Database (Denmark)

    Zeka, Bleranda; Hastermann, Maria; Hochmeister, Sonja;

    2015-01-01

    In neuromyelitis optica (NMO), astrocytes become targets for pathogenic aquaporin 4 (AQP4)-specific antibodies which gain access to the central nervous system (CNS) in the course of inflammatory processes. Since these antibodies belong to a T cell-dependent subgroup of immunoglobulins, and since...

  17. Structural Alterations of Segmented Macular Inner Layers in Aquaporin4-Antibody-Positive Optic Neuritis Patients in a Chinese Population.

    Directory of Open Access Journals (Sweden)

    Chunxia Peng

    Full Text Available This study aimed to analyse the structural injury of the peripapillary retinal nerve fibre layer (pRNFL and segmented macular layers in optic neuritis (ON in aquaporin4-antibody (AQP4-Ab seropositivity(AQP4-Ab-positiveON patients and in AQP4-Ab seronegativity (AQP4-Ab-negative ON patients in order to evaluate their correlations with the best-corrected visual acuity (BCVA and the value of the early diagnosis of neuromyelitis optica (NMO.This is a retrospective, cross-sectional and control observational study.In total, 213 ON patients (291 eyes and 50 healthy controls (HC (100 eyes were recruited in this study. According to a serum AQP4-Ab assay, 98 ON patients (132 eyes were grouped as AQP4-Ab-positive ON and 115 ON patients (159 eyes were grouped as AQP4-Ab-negative ON cohorts. All subjects underwent scanning with spectralis optical coherence tomography (OCT and BCVA tests. pRNFL and segmented macular layer measurements were analysed.The pRNFL thickness in AQP4-Ab-positive ON eyes showed a more serious loss during 0-2 months (-27.61μm versus -14.47 μm and ≥6 months (-57.91μm versus -47.19μm when compared with AQP4-Ab-negative ON eyes. AQP4-Ab-positive ON preferentially damaged the nasal lateral pRNFL. The alterations in the macular ganglion cell layer plus the inner plexiform layer (GCIP in AQP4-Ab-positive ON eyes were similar to those in AQP4-Ab-negative ON eyes. AQP4-Ab-positive ON eyes had entirely different injury patterns in the inner nuclear layer (INL compared with AQP4-Ab-negative ON eyes during the first 6 months after the initial ON attack. These differences were as follows: the INL volume of AQP4-Ab-positive ON eyes had a gradual growing trend compared with AQP4-Ab-negative ON eyes, and it increased rapidly during 0-2 months, reached its peak during 2-4 months, and then decreased gradually. The pRNFL and GCIP in AQP4-Ab-positive ON eyes had positive correlations with BCVA. When the pRNFL thickness decreased to 95%CI (50.77

  18. Propofol Attenuates Early Brain Injury After Subarachnoid Hemorrhage in Rats.

    Science.gov (United States)

    Shi, Song-sheng; Zhang, Hua-bin; Wang, Chun-hua; Yang, Wei-zhong; Liang, Ri-sheng; Chen, Ye; Tu, Xian-kun

    2015-12-01

    Our previous studies demonstrated that propofol protects rat brain against focal cerebral ischemia. However, whether propofol attenuates early brain injury after subarachnoid hemorrhage in rats remains unknown until now. The present study was performed to evaluate the effect of propofol on early brain injury after subarachnoid hemorrhage in rats and further explore the potential mechanisms. Sprague-Dawley rats underwent subarachnoid hemorrhage (SAH) by endovascular perforation then received treatment with propofol (10 or 50 mg/kg) or vehicle after 2 and 12 h of SAH. SAH grading, neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and malondialdehyde (MDA) content were measured 24 h after SAH. Expression of nuclear factor erythroid-related factor 2 (Nrf2), nuclear factor-kappa B (NF-κB) p65, and aquaporin 4 (AQP4) expression in rat brain were detected by Western blot. Expression of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) were determined by reverse transcription-polymerase chain reaction (RT-PCR). Expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were assessed by ELISA. Neurological scores, brain water content, Evans blue extravasation, the myeloperoxidase activity, and MDA content were significantly reduced by propofol. Furthermore, expression of Nrf2 in rat brain was upregulated by propofol, and expression of NF-κB p65, AQP4, COX-2, MMP-9, TNF-α, and IL-1β in rat brain were attenuated by propofol. Our results demonstrated that propofol improves neurological scores, reduces brain edema, blood-brain barrier (BBB) permeability, inflammatory reaction, and lipid peroxidation in rats of SAH. Propofol exerts neuroprotection against SAH-induced early brain injury, which might be associated with the inhibition of inflammation and lipid peroxidation. PMID:26342279

  19. Efficacy of Polyvalent Human Immunoglobulins in an Animal Model of Neuromyelitis Optica Evoked by Intrathecal Anti-Aquaporin 4 Antibodies

    Directory of Open Access Journals (Sweden)

    Benedikt Grünewald

    2016-08-01

    Full Text Available Neuromyelitis Optica Spectrum Disorders (NMOSD are associated with autoantibodies (ABs targeting the astrocytic aquaporin-4 water channels (AQP4-ABs. These ABs have a direct pathogenic role by initiating a variety of immunological and inflammatory processes in the course of disease. In a recently-established animal model, chronic intrathecal passive-transfer of immunoglobulin G from NMOSD patients (NMO-IgG, or of recombinant human AQP4-ABs (rAB-AQP4, provided evidence for complementary and immune-cell independent effects of AQP4-ABs. Utilizing this animal model, we here tested the effects of systemically and intrathecally applied pooled human immunoglobulins (IVIg using a preventive and a therapeutic paradigm. In NMO-IgG animals, prophylactic application of systemic IVIg led to a reduced median disease score of 2.4 on a 0–10 scale, in comparison to 4.1 with sham treatment. Therapeutic IVIg, applied systemically after the 10th intrathecal NMO-IgG injection, significantly reduced the disease score by 0.8. Intrathecal IVIg application induced a beneficial effect in animals with NMO-IgG (median score IVIg 1.6 vs. sham 3.7 or with rAB-AQP4 (median score IVIg 2.0 vs. sham 3.7. We here provide evidence that treatment with IVIg ameliorates disease symptoms in this passive-transfer model, in analogy to former studies investigating passive-transfer animal models of other antibody-mediated disorders.

  20. SIRT2 inhibition exacerbates neuroinflammation and blood-brain barrier disruption in experimental traumatic brain injury by enhancing NF-κB p65 acetylation and activation.

    Science.gov (United States)

    Yuan, Fang; Xu, Zhi-Ming; Lu, Li-Yan; Nie, Hui; Ding, Jun; Ying, Wei-Hai; Tian, Heng-Li

    2016-02-01

    Sirtuin 2 (SIRT2) is a member of the sirtuin family of NAD(+) -dependent protein deacetylases. In recent years, SIRT2 inhibition has emerged as a promising treatment for neurodegenerative diseases. However, to date, there is no evidence of a specific role for SIRT2 in traumatic brain injury (TBI). We investigated the effects of SIRT2 inhibition on experimental TBI using the controlled cortical impact (CCI) injury model. Adult male mice underwent CCI or sham surgery. A selective brain-permeable SIRT2 inhibitor, AK-7, was administrated 30 min before injury. The volume of the brain edema lesion and the water content of the brain were significantly increased in mice treated with AK-7 (20 mg/kg), compared with the vehicle group, following TBI (p aquaporin 4 (AQP4), MMP-9, and pro-inflammatory cytokines. Together, these data demonstrate that SIRT2 inhibition exacerbates TBI by increasing NF-κB p65 acetylation and activation. Our findings provide additional evidence of an anti-inflammatory effect of SIRT2. SIRT2 is a member of the sirtuin family of NAD+-dependent protein deacetylases. Our study suggests that the SIRT2 inhibitor AK-7 exacerbates traumatic brain injury (TBI) via a potential mechanism involving increased acetylation and nuclear translocation of NF-κB p65, resulting in up-regulation of NF-κB target genes, including aquaporin 4 (AQP4), matrix metalloproteinase 9 (MMP-9), and pro-inflammatory cytokines. Our findings provide additional evidence of an anti-inflammatory effect of SIRT2. PMID:26546505

  1. Study on the effect and mechanism of agmatine on blood brain barrier with cerebral ischemic reperfusion injury rats%胍丁胺对脑缺血再灌注损伤大鼠血脑屏障的作用机制研究

    Institute of Scientific and Technical Information of China (English)

    郑立霞; 徐鑫淼; 郎现波; 张秀丽; 杨美子

    2015-01-01

    目的:研究胍丁胺对血脑屏障( BBB )通透性的影响及其与水通道蛋白( AQP)的相关性。方法将大鼠随机分为假手术组、实验组和模型组。大脑中动脉栓塞2 h后,实验组和模型组分别腹腔注射胍丁胺(50 mg · kg-1)和等量0.9%NaCl。通过测定脑水含量、BBB通透性,考察BBB的损害程度,用2,3,5-氯化三苯基四氮唑(TTC)染色法比较梗死灶大小,苏木精-伊红(HE)染色和电镜观察神经元形态学变化,Western-blotting法检测AQP4、AQP9的表达。结果实验组BBB通透性显著下降,变性神经元数明显减少,同时, AQP4与AQP9的表达较模型组显著降低。结论胍丁胺通过降低AQP4、AQP9的表达来改善BBB通透性,从而减轻脑水肿引起的神经元损伤。%Objective To observe the effect of agmatine on brain ede-ma and examine the relation between blood brain barrier ( BBB) per-meability and aquaporin 4 ( AQP4 ) and aquaporin 9 ( AQP9 ) in rats with cerebral ischemic reperfusion.Methods Health male Sprague-Dawley rats were randomly divided into sham group , model group and test ( agmatine ) group.And 2 h after middle cerebral artery occlusion, giving agmatine ( 50 mg · kg -1 ) in test group or 0.9%NaCl in sham and model groups by intraperitoneal injection, respec-tively.Brain edema and the size of the brain infarct were assayed by brain water content and BBB permeability and 2,3,5 -triphenyltet-razoliumchloridstaining( TTC).The morphological changes of neurons were observed by hematoxylin and eosin staining and transmission electron microscopy.And the expression of AQP4 and AQP9 were assessed by Western -blotting.Results The BBB permeability de-creased significantly and the morphological changes of neurons were reduced significantly and the expression of AQP4 and AQP9 decreased significantly in rats with agmatine.Conclusion Agmatine reduce the injury of the BBB by decreasing the expression of AQP4 and

  2. Human Aquaporin-4 and Molecular Modeling: Historical Perspective and View to the Future

    Directory of Open Access Journals (Sweden)

    Giuseppe Felice Mangiatordi

    2016-07-01

    Full Text Available Among the different aquaporins (AQPs, human aquaporin-4 (hAQP4 has attracted the greatest interest in recent years as a new promising therapeutic target. Such a membrane protein is, in fact, involved in a multiple sclerosis-like immunopathology called Neuromyelitis Optica (NMO and in several disorders resulting from imbalanced water homeostasis such as deafness and cerebral edema. The gap of knowledge in its functioning and dynamics at the atomistic level of detail has hindered the development of rational strategies for designing hAQP4 modulators. The application, lately, of molecular modeling has proved able to fill this gap providing a breeding ground to rationally address compounds targeting hAQP4. In this review, we give an overview of the important advances obtained in this field through the application of Molecular Dynamics (MD and other complementary modeling techniques. The case studies presented herein are discussed with the aim of providing important clues for computational chemists and biophysicists interested in this field and looking for new challenges.

  3. Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays

    Directory of Open Access Journals (Sweden)

    Chan Koon H

    2010-09-01

    Full Text Available Abstract Background Neuromyelitis optica spectrum disorders (NMOSD are severe central nervous system inflammatory demyelinating disorders (CNS IDD characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM and/or optic neuritis (ON. A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4 autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA and cell-based IIFA. Methods Serum of Chinese CNS IDD patients were assayed for AQP4 autoantibodies by tissue-based IIFA using monkey cerebellum and cell-based IIFA using transfected HEK293 cells which express human AQP4 on their cell membranes. Results In total, 128 CNS IDD patients were studied. We found that 78% of NMO patients were seropositive for AQP4 autoantibodies by cell-based IIFA versus 61% by tissue-based IFA (p = 0.250, 75% of patients having relapsing myelitis (RM with LETM were seropositive by cell-based IIFA versus 50% by tissue-based IIFA (p = 0.250, and 33% of relapsing ON patients were seropositive by cell-based IIFA versus 22% by tissue-based IIFA (p = 1.000; however the differences were not statistically significant. All patients seropositive by tissue-based IIFA were also seropositive for AQP4 autoantibodies by cell-based IIFA. Among 29 NMOSD patients seropositive for AQP4 autoantibodies by cell-based IIFA, 20 (69% were seropositive by tissue-based IIFA. The 9 patients seropositive by cell-based IIFA while seronegative by tissue-based IIFA had NMO (3, RM with LETM (3, a single attack of LETM (1, relapsing ON (1 and a single ON attack (1. Among 23 NMO or RM patients seropositive for AQP4 autoantibodies by cell-based IIFA, comparison between those seropositive (n = 17 and seronegative (n = 6 by tissue-based IIFA revealed no differences in clinical and neuroradiological characteristics between the two groups. Conclusion Cell-based IIFA is slightly more sensitive

  4. The change of metabotropic glutamate receptor 5 expression level in rats with late-stage traumatic brain injury and the therapeutic effect of taurine

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    Ying CAI

    2016-08-01

    Full Text Available Objective To investigate the change of metabotropic glutamate receptor 5 (mGluR5 expression level in rats with late-stage (the 7th day traumatic brain injury (TBI and the role of taurine. Methods The left cerebral TBI rat models were made by using lateral fluid percussion method. A total of 30 specific pathogen free (SPF male Sprague-Dawley (SD rats were randomly divided into 3 groups: sham operation group (control group, TBI model group (TBI group and taurine treatment group (taurine group. Wet and dry weight method was used to measure the brain water content. Real-time fluorescent quantitative polymerase chain reaction (PCR and Western blotting were used to detect the change of mRNA and protein expression of aquaporin 4 (AQP4 and mGluR5 in each group.  Results Compared with control group, the brain water content (t = 4.893, P = 0.002, AQP4 mRNA (t = 6.523, P = 0.000 and protein (t = 4.366, P = 0.008 expression were upregulated, while mGluR5 mRNA (t = 5.776, P = 0.001 and protein (t = 3.945, P = 0.014 expression were downregulated in TBI group. After taurine treatment, the brain water content (t = 2.151, P = 0.140, AQP4 mRNA (t = 1.144,P = 0.432 and protein (t = 0.367, P = 0.804 decreased to normal, while mGluR5 mRNA (t = 1.824, P = 0.216 and protein (t = 1.185, P = 0.414 increased to normal. Correlation analysis showed brain water content was negatively correlated with mGluR5 mRNA (r = -0.617, P = 0.014 and mGluR5 protein (r = -0.665, P = 0.007, while it was positively correlated with AQP4 protein (r = 0.658, P = 0.008.  Conclusions Taurine can significantly increase the mGluR5 expression level of brain issue in the late-stage (the 7th day of TBI and decline brain edema and brain water content. It may be a potential protective agent as an inhibitory neurotransmitter. DOI: 10.3969/j.issn.1672-6731.2016.08.008

  5. Enhanced Expression of Aquaporin-9 in Rat Brain Edema Induced by Bacterial Lipopolysaccharides

    Institute of Scientific and Technical Information of China (English)

    Huaili WANG; Runming JIN; Peichao TIAN; Zhihong ZHUO

    2009-01-01

    To investigate the role of AQP9 in brain edema,the expression of AQP9 in an infectious rat brain edema model induced by the injection of lipopolysaccharide (LPS) was examined.Immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that the expressions of AQP9 mRNA and protein at all observed intervals were significantly increased in LPS-treated animals in comparison with the control animals.Time-course analysis showed that the first signs of blood-brain barrier disruption and the increase of brain water content in LPS-treated animals were evident 6 h after LPS injection,with maximum value appearing at 12 h,which coincided with the expression profiles of AQP9 mRNA and protein in LPS-treated animals.The further correlation analysis revealed strong positive correlations among the brain water content,the disruption of the blood-brain barrier and the enhanced expressions of AQP9 mRNA and protein in LPS-treated animals.These results suggested that the regulation of AQP9 expression may play important roles in water movement and in brain metabolic homeostasis associated with the pathophysiology of brain edema induced by LPS injection.

  6. Association Between the Single Nucleotide Polymorphism and the Level of Aquaporin-4 Protein Expression in Han and Minority Chinese with Inflammatory Demyelinating Diseases of the Central Nervous System.

    Science.gov (United States)

    Chu, Lan; Dai, Qingqing; Xu, Zhu; He, Dian; Wang, Hao; Wang, Qingsong; Zhang, Yifan; Zhu, Yingwu; Li, Yuan; Cai, Gang; Slavica, Krantic; Allan, Kermode

    2016-07-01

    The purpose of this study was to determine whether or not aquaporin-4 (AQP4) gene mutations are related to the pathogenesis of inflammatory demyelinating diseases in the central nervous system. Polymorphisms of AQP4 exons 1-5 were determined by sequencing DNA from 67 patients with central nervous system inflammatory demyelinating diseases, including neuromyelitis optica (NMO), multiple sclerosis, recurrent or simultaneous bilateral optic neuritis, and longitudinally extensive transverse myelitis. A plasmid with the identified new missense mutation was constructed, and human embryonic kidney cells (HEK293A) were transfected with either the pEGFP-N1-AQP4-M23 vector (bearing the identified mutated cDNA sequence) or with the plasmid bearing the wild-type AQP4 gene sequence. AQP4 protein expression was analyzed in both experimental groups using Western Blot analysis following protein extraction from transfected cells. A synonymous mutation (rs1839318) was detected on exon 3, and an additional synonymous mutation was detected on the exon 2-2 (rs72557968). Most importantly, a new missense mutation was detected on exon 2-1. According to Western blot analysis, the mutated cDNA sequence yielded increased AQP4 protein expression in comparison with the wild-type cDNA sequence (P < 0.05). AQP4 gene mutations are uncommon, occurring in only 3 out of 67 patients. Although it is possible that the mutations contributed to an increased risk of inflammatory central nervous system disease in these individuals, it is unlikely that mutations are a significant contributor to most patients with NMO spectrum disorders in China. PMID:25895050

  7. Effects of estradiol on ischemic factor-induced astrocyte swelling and AQP4 protein abundance

    OpenAIRE

    Rutkowsky, Jennifer M.; Wallace, Breanna K.; Wise, Phyllis M.; O'Donnell, Martha E.

    2011-01-01

    In the early hours of ischemic stroke, cerebral edema forms as Na, Cl, and water are secreted across the blood-brain barrier (BBB) and astrocytes swell. We have shown previously that ischemic factors, including hypoxia, aglycemia, and arginine vasopressin (AVP), stimulate BBB Na-K-Cl cotransporter (NKCC) and Na/H exchanger (NHE) activities and that inhibiting NKCC and/or NHE by intravenous bumetanide and/or HOE-642 reduces edema and infarct in a rat model of ischemic stroke. Estradiol also re...

  8. 水通道蛋白-4抗体阳性患者的诊断%Retrospective analysis of the diagnosis of patients with positive aquaporin-4 antibody

    Institute of Scientific and Technical Information of China (English)

    何毅华; 龙友明; 杨新光; 杨宁; 范永祥; 殷建瑞; 蒲蜀湘; 高庆春; 高聪

    2014-01-01

    目的:对水通道蛋白-4( AQP4)抗体阳性患者进行重新诊断,并回顾分析患者的以往诊断,从而有助于加强对视神经脊髓炎(NMO)及其谱系疾病(NMOSD)的再认识,指导进一步的诊治。方法 AQP4抗体通过间接免疫荧光的细胞法检测。回顾性分析AQP4抗体阳性患者的不同时期诊断。结果139例AQP4抗体阳性患者被纳入本研究。首次发作的临床诊断如下:7例(5.0%)NMO,20例(14.4%)多发性硬化(MS),39例(28.1%)视神经炎(ON),59例(42.4%)脊髓炎(TM),其他诊断14例(10.1%)。病程中的修正诊断如下:33例(23.7%) NMO,68例(48.9%) MS,8例(5.8%) ON,28例(20.1%) TM,其他诊断2例(1.4%)。最终诊断如下:88例(63.3%)NMO,51例(36.7%)NMOSD,包括了7例(13.7%,7/51)复发性ON,39例(76.5%,39/51)复发性TM和5例(9.8%,5/51)无ON、TM的NMOSD。最终的88例NMO患者中,52例(59.1%)被误诊为MS。结论AQP4抗体阳性患者常被误诊为MS。%Objective To analyze the diagnosis of patients with positive aquaporin -4 (AQP4) antibody, and to re-evaluate the previous diagnosis , thus to provide evidences for diagnosis and treatment for patients with neuromyelitis optica ( NMO) and NMO spectrum disorder ( NMOSD) .Methods AQP4 antibodies were tested by an indirect immuno-fluorescence assay employing HEK -293 cells transected with recombinant human AQP 4.Clinical diagnoses were retro-spectively analyzed.Results A total of 139 patients with positive AQP4 antibody were included.In the initial episode, NMO, multiple sclerosis ( MS) , optic neuritis ( ON) , transverse myelitis ( TM) and the other diagnosis were diagnosed in 7 (5%), 20 (14.4%), 39 (28.1%), 59 (42.4%) and 14 (10.1%) patients, respectively.In the follow-up, ac-cording to revised diagnosis, NMO, MS, ON, TM and other disorders were diagnosed in 33 (23.7%), 68 (48

  9. Renal aquaporins and water balance disorders

    DEFF Research Database (Denmark)

    Kortenoeven, Marleen; Fenton, Robert A.

    2013-01-01

    BACKGROUND: Aquaporins (AQPs) are a family of proteins that can act as water channels. Regulation of AQPs is critical to osmoregulation and the maintenance of body water homeostasis. Eight AQPs are expressed in the kidney of which five have been shown to play a role in body water balance; AQP1, A......-solute diet and diuretics. GENERAL SIGNIFICANCE: In recent years, our understanding of the underlying mechanisms of water balance disorders has increased enormously, which has opened up several possible new treatment strategies.......BACKGROUND: Aquaporins (AQPs) are a family of proteins that can act as water channels. Regulation of AQPs is critical to osmoregulation and the maintenance of body water homeostasis. Eight AQPs are expressed in the kidney of which five have been shown to play a role in body water balance; AQP1, AQP......2, AQP3, AQP4 and AQP7. AQP2 in particular is regulated by vasopressin. SCOPE OF REVIEW: This review summarizes our current knowledge of the underlying mechanisms of various water balance disorders and their treatment strategies. MAJOR CONCLUSIONS: Dysfunctions of AQPs are involved in disorders...

  10. Changes in aquaporin-4 and Kir4.1 expression in rats with inherited retinal dystrophy.

    Science.gov (United States)

    Lassiale, S; Valamanesh, F; Klein, C; Hicks, D; Abitbol, M; Versaux-Botteri, C

    2016-07-01

    Muller glial cells (MGC) are essential for normal functioning of retina. They are especially involved in potassium (K+) and water homeostasis, via inwardly rectifying K+ (Kir 4.1) and aquaporin-4 (AQP4) channels respectively. Because MGC appear morphologically and functionally altered in most retinal pathologies, we studied the expression of AQP 4 and Kir 4.1 during the time course of progressive retinal degeneration in Royal College of Surgeons (RCS) rats, an animal model for the hereditary human retinal degenerative disease Retinitis pigmentosa. Simultaneous detection of AQP4 and Kir 4.1 was performed by quantitative real-time polymerase chain reaction (QRT-PCR), Western blot and immunohistochemistry at birth and during progression of the pathology. Although small quantities of AQP4 and Kir 4.1 mRNA were detected at birth (postnatal day (PNd) 0) in both control and dystrophic rat retinas, proteins could not be detected at this age. Detectable proteins appeared in the second week of postnatal life. From PNd15 onwards, the time course in the expression of both AQP4 and Kir 4.1 mRNAs and protein was similar in dystrophic and control rats, with a progressive increase peaking at PNd60 and a subsequent decrease by one year. AQP4 protein and mRNA content were significantly lowered in dystrophic compared to control rats. Kir 4.1 protein levels were also lower in dystrophic retinas, while mRNA concentrations were unchanged and/or slightly higher in dystrophic rats. The discrepancies between Kir4.1 mRNA and protein suggest perturbation in protein translation due to the pathology. AQP4 and Kir 4.1/vimentin co-immunolabeling showed that: 1) apical radial processes of some MGC invaded the subretinal zone, and 2) MGC morphology was distorted in advanced pathology. MGC became hypertrophic both during the pathology and also with age in control rats. In conclusion, our results confirm that this inherited photoreceptor degeneration also leads to progressive alterations in

  11. Protective Effect effect of Flavonoids flavonoids from Polygala Polygala Hongkongensis on the Blood blood Brain brain Barrier barrier in Rats rats with Focal focal Cerebral cerebral Ischemia ischemia Reperfusion reperfusion%香港远志黄酮苷对局灶性脑缺血再灌注大鼠血脑屏障的保护及作用机制

    Institute of Scientific and Technical Information of China (English)

    詹海涛; 吴剑峰; 李海燕; 孟红旗; 曾煦欣

    2012-01-01

    Objective To investigate the influence of flavonoids from Polygala Hongkongensis( FPH) on the permeability of Blood blood Brain brain Barrierbarrier ( BBB) , brain water content and expression of matrix metalloproleinase-9 ( MMP-9) 、and aquaporin 4( AQP4) in rats with focal cerebral ischemia reperfusion(IR). Methods SD rats were randomly divided into sham operated group ", model group and treatment groups (the treatment groups were divided into Kaempferol-3-O-rutinoside( PHN-08 ) 、and kaempferol-3-0-glucoside( PHN-11) and combined formula group. Treatment groups received drug respectively according to grouping protocol, the sham operated and model groups received infusions of normal saline. The method of middle cerebral artery occlusion ( MCAO) by thread approach was used to establish the model of focal brain ischemia reperfusion(IR) IR. At the IR 24h and 48h,the mount of Evan' s blue( EB) exudation of the brain tissue、brain water content and expression of MMP-9 、and AQP4 were observed. Results At the IR 24h and 48h,compared with that of the sham operated group,the mount of EB exudationNbrain water content and expression of MMP-9 and、AQP4 were significantly increased in both of the model and treatment groups(P <0. 05). Compared with that of the model group,the mount of EB exudatioexudation, n, brain water content and expression of MMP-9 and 、 AQP4 were significantly decreased in the treatment groups( P <0. 05). Conclusion The FPH given prior to the rats with focal cerebral IR plays a protective role on the BBB,which may be achieved by decreasing the expression of MMP-9 and AQP4.%目的 探讨香港远志黄酮苷预处理,对局灶性脑缺血再灌注大鼠血脑屏障(BBB)通透性、脑含水量、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)及水通道蛋白4(aquaporin 4,AQP4)表达的影响.方法 线栓法制备SD大鼠大脑中动脉闭塞(MCAO)局灶性脑缺血再灌注模型,随机分假手术组、模型组、山柰酚-3-O

  12. The speed of swelling kinetics modulates cell volume regulation and calcium signaling in astrocytes: A different point of view on the role of aquaporins.

    Science.gov (United States)

    Mola, Maria Grazia; Sparaneo, Angelo; Gargano, Concetta Domenica; Spray, David C; Svelto, Maria; Frigeri, Antonio; Scemes, Eliana; Nicchia, Grazia Paola

    2016-01-01

    Regulatory volume decrease (RVD) is a process by which cells restore their original volume in response to swelling. In this study, we have focused on the role played by two different Aquaporins (AQPs), Aquaporin-4 (AQP4), and Aquaporin-1 (AQP1), in triggering RVD and in mediating calcium signaling in astrocytes under hypotonic stimulus. Using biophysical techniques to measure water flux through the plasma membrane of wild-type (WT) and AQP4 knockout (KO) astrocytes and of an astrocyte cell line (DI TNC1) transfected with AQP4 or AQP1, we here show that AQP-mediated fast swelling kinetics play a key role in triggering and accelerating RVD. Using calcium imaging, we show that AQP-mediated fast swelling kinetics also significantly increases the amplitude of calcium transients inhibited by Gadolinium and Ruthenium Red, two inhibitors of the transient receptor potential vanilloid 4 (TRPV4) channels, and prevented by removing extracellular calcium. Finally, inhibition of TRPV4 or removal of extracellular calcium does not affect RVD. All together our study provides evidence that (1) AQP influenced swelling kinetics is the main trigger for RVD and in mediating calcium signaling after hypotonic stimulus together with TRPV4, and (2) calcium influx from the extracellular space and/or TRPV4 are not essential for RVD to occur in astrocytes. PMID:26413835

  13. Aquaporin-4 Immuneglobulin G testing in 36 consecutive Jamaican patients with inflammatory central nervous system demyelinating disease

    Directory of Open Access Journals (Sweden)

    Sherri Sandy

    2014-08-01

    Full Text Available Epidemiological studies of neuromyelitis optica (NMO in Jamaica are lacking. Here we reviewed the clinical records of 700 patients undergoing neurological evaluation at the Kingston Public Hospital, the largest tertiary institution in Jamaica over a 4 month period. We investigated the diagnostic utility of Aquaporin-4 ImmuneglobulinG (AQP4-IgG testing in 36 consecutive patients with a diagnosis of an inflammatory demyelinating disorder (IDD of the central nervous system (CNS. Patients were classified into 3 categories: i NMO, n=10; ii multiple sclerosis (MS, n=14 and iii unclassified IDD (n=12. All sera were tested for AQP-IgG status by cell binding assay (Euroimmun. No MS cases were positive. Ninety per cent of NMO cases were positive. Four of 12 patients with unclassified IDD tested positive for AQP4-IgG. AQP4-IgG seropositivity was associated with a lower socioeconomic status, higher EDSS (P=0.04 and lower pulmonary function than the seronegative cases (P=0.007. Aquaporin-4 autoimmunity may account for a significant proportion of Jamaican CNS IDDs.

  14. Attenuation of Acute Phase Injury in Rat Intracranial Hemorrhage by Cerebrolysin that Inhibits Brain Edema and Inflammatory Response.

    Science.gov (United States)

    Yang, Yang; Zhang, Yan; Wang, Zhaotao; Wang, Shanshan; Gao, Mou; Xu, Ruxiang; Liang, Chunyang; Zhang, Hongtian

    2016-04-01

    The outcome of intracerebral hemorrhage (ICH) is mainly determined by the volume of the hemorrhage core and the secondary brain damage to penumbral tissues due to brain swelling, microcirculation disturbance and inflammation. The present study aims to investigate the protective effects of cerebrolysin on brain edema and inhibition of the inflammation response surrounding the hematoma core in the acute stage after ICH. The ICH model was induced by administration of type VII bacterial collagenase into the stratum of adult rats, which were then randomly divided into three groups: ICH + saline; ICH + Cerebrolysin (5 ml/kg) and sham. Cerebrolysin or saline was administered intraperitoneally 1 h post surgery. Neurological scores, extent of brain edema content and Evans blue dye extravasation were recorded. The levels of pro-inflammatory factors (IL-1β, TNF-α and IL-6) were assayed by Real-time PCR and Elisa kits. Aquaporin-4 (AQP4) and tight junction proteins (TJPs; claudin-5, occludin and zonula occluden-1) expression were measured at multiple time points. The morphological and intercellular changes were characterized by Electron microscopy. It is found that cerebrolysin (5 ml/kg) improved the neurological behavior and reduced the ipsilateral brain water content and Evans blue dye extravasation. After cerebrolysin treated, the levels of pro-inflammatory factors and AQP4 in the peri-hematomal areas were markedly reduced and were accompanied with higher expression of TJPs. Electron microscopy showed the astrocytic swelling and concentrated chromatin in the ICH group and confirmed the cell junction changes. Thus, early cerebrolysin treatment ameliorates secondary injury after ICH and promotes behavioral performance during the acute phase by reducing brain edema, inflammatory response, and blood-brain barrier permeability. PMID:26498936

  15. Dynamic regulation of aquaporin-4 water channels in neurological disorders.

    Science.gov (United States)

    Hsu, Ying; Tran, Minh; Linninger, Andreas A

    2015-10-01

    Aquaporin-4 water channels play a central role in brain water regulation in neurological disorders. Aquaporin-4 is abundantly expressed at the astroglial endfeet facing the cerebral vasculature and the pial membrane, and both its expression level and subcellular localization significantly influence brain water transport. However, measurements of aquaporin-4 levels in animal models of brain injury often report opposite trends of change at the injury core and the penumbra. Furthermore, aquaporin-4 channels play a beneficial role in brain water clearance in vasogenic edema, but a detrimental role in cytotoxic edema and exacerbate cell swelling. In light of current evidence, we still do not have a complete understanding of the role of aquaporin-4 in brain water transport. In this review, we propose that the regulatory mechanisms of aquaporin-4 at the transcriptional, translational, and post-translational levels jointly regulate water permeability in the short and long time scale after injury. Furthermore, in order to understand why aquaporin-4 channels play opposing roles in cytotoxic and vasogenic edema, we discuss experimental evidence on the dynamically changing osmotic gradients between blood, extracellular space, and the cytosol during the formation of cytotoxic and vasogenic edema. We conclude with an emerging picture of the distinct osmotic environments in cytotoxic and vasogenic edema, and propose that the directions of aquaporin-4-mediated water clearance in these two types of edema are distinct. The difference in water clearance pathways may provide an explanation for the conflicting observations of the roles of aquaporin-4 in edema resolution. PMID:26526878

  16. Evidence of Positive Selection of Aquaporins Genes from Pontoporia blainvillei during the Evolutionary Process of Cetaceans.

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    Simone Lima São Pedro

    Full Text Available Marine mammals are well adapted to their hyperosmotic environment. Several morphological and physiological adaptations for water conservation and salt excretion are known to be present in cetaceans, being responsible for regulating salt balance. However, most previous studies have focused on the unique renal physiology of marine mammals, but the molecular bases of these mechanisms remain poorly explored. Many genes have been identified to be involved in osmotic regulation, including the aquaporins. Considering that aquaporin genes were potentially subject to strong selective pressure, the aim of this study was to analyze the molecular evolution of seven aquaporin genes (AQP1, AQP2, AQP3, AQP4, AQP6, AQP7, and AQP9 comparing the lineages of cetaceans and terrestrial mammals.Our results demonstrated strong positive selection in cetacean-specific lineages acting only in the gene for AQP2 (amino acids 23, 83, 107,179, 180, 181, 182, whereas no selection was observed in terrestrial mammalian lineages. We also analyzed the changes in the 3D structure of the aquaporin 2 protein. Signs of strong positive selection in AQP2 sites 179, 180, 181, and 182 were unexpectedly identified only in the baiji lineage, which was the only river dolphin examined in this study. Positive selection in aquaporins AQP1 (45, AQP4 (74, AQP7 (342, 343, 356 was detected in cetaceans and artiodactyls, suggesting that these events are not related to maintaining water and electrolyte homeostasis in seawater.Our results suggest that the AQP2 gene might reflect different selective pressures in maintaining water balance in cetaceans, contributing to the passage from the terrestrial environment to the aquatic. Further studies are necessary, especially those including other freshwater dolphins, who exhibit osmoregulatory mechanisms different from those of marine cetaceans for the same essential task of maintaining serum electrolyte balance.

  17. Loss of aquaporin-4 expression and putative function in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Aquaporins (AQPs) have been recognized to promote tumor progression, invasion, and metastasis and are therefore recognized as promising targets for novel anti-cancer therapies. Potentially relevant AQPs in distinct cancer entities can be determined by a comprehensive expression analysis of the 13 human AQPs. We analyzed the presence of all AQP transcripts in 576 different normal lung and non-small cell lung cancer (NSCLC) samples using microarray data and validated our findings by qRT-PCR and immunohistochemistry. Variable expression of several AQPs (AQP1, -3, -4, and -5) was found in NSCLC and normal lung tissues. Furthermore, we identified remarkable differences between NSCLC subtypes in regard to AQP1, -3 and -4 expression. Higher transcript and protein levels of AQP4 in well-differentiated lung adenocarcinomas suggested an association with a more favourable prognosis. Beyond water transport, data mining of co-expressed genes indicated an involvement of AQP4 in cell-cell signalling, cellular movement and lipid metabolism, and underlined the association of AQP4 to important physiological functions in benign lung tissue. Our findings accentuate the need to identify functional differences and redundancies of active AQPs in normal and tumor cells in order to assess their value as promising drug targets

  18. Anti-aquaporin-4 IgG in patients presenting with unilateral optic neuritis: A cohort study

    Directory of Open Access Journals (Sweden)

    Masoud Etemadifar

    2012-01-01

    Full Text Available Background: Optic neuritis (ON can be the first presentation of multiple sclerosis (MS or neuromyelitis optica (NMO. Anti-aquaporin-4 IgG (AQP4 IgG is a highly specific and moderately sensitive biomarker for NMO. This study was designed to assess the rate of seropositivity for AQP4 IgG, and the short-term outcome of patients presenting with single isolated ON (SION. Methods: A cohort of 41 consecutive patients experiencing severe (< 20 / 200 SION (not fulfilling the diagnostic criteria for MS or NMO, was prospectively recruited. Blood sampling was carried out immediately after the diagnosis of ON, and AQP4 IgG was tested qualitatively, using an indirect immunofluorescence kit. After clinical and paraclinical investigations, all the patients were followed up for a short-term period of at least 18 months. Results: The seroprevalence among the initial ON patients was 9.7% (4 / 41. The short-term conversion rate to MS and NMO was estimated to be about 7.3 and 4.9%, respectively. The conversion rate to NMO in initially seropositive patients was greater than that for the whole cohort [2 / 4 (50% vs. 2 / 41 (4.9%; P = 0.035; Odds ratio: 19.5, 95% confidence interval: 1.73 to 219.50]. Conclusion: AQP4 IgG seropositive SION patients were more likely to develop NMO in comparison to the total SION population. Further studies, with a longer follow-up period and larger sample sizes are warranted to assess the clinical and prognostic value of assessing AQP4 IgG in SION.

  19. Optic neuritis: a 5-year follow-up study of Chinese patients based on aquaporin-4 antibody status and ages.

    Science.gov (United States)

    Zhou, Huanfen; Zhao, Shuo; Yin, Dongfang; Chen, Xiaofei; Xu, Quangang; Chen, Tingjun; Li, Xiaoyan; Wang, Junqing; Li, Hongyang; Peng, Chunxia; Lin, Dahe; Wei, Shihui

    2016-07-01

    Little work has been performed on the long-term outcome of optic neuritis (ON) according to the status of aquaporin-4 antibody (AQP4-Ab) and long-term prognosis in older patients in China. This study retrospectively analyzed medical records in a cohort of Chinese patients with 5-year follow-up according to AQP4-Ab status and ages from January 2009 to December 2010. The clinical features, laboratory findings and risk factors for prognosis were analyzed. A total of 128 ON patients were included, 66.4 % of whom were female. The median age at onset was 36.8 years (range 18-73). Serum AQP4-Ab was positive in 45 (35.2 %) patients, with greater frequency in the female, bilateral, and recurrent ON groups (48.2, 42.5 and 53.6 %, respectively). Seropositive AQP4-Ab ON patients had worse visual recovery compared to seronegative patients (p = 0.033). The average and four quadrants of retinal nerve fiber layer (RNFL) thickness were significantly thinner in the seropositive group than in the seronegative group (p transverse myelitis (TM) episode were ocular pain and recurrence within 1 year. The older patients had worse visual outcome after the first episode of ON than the younger patients (p = 0.007). However, the two groups did not differ significantly with regard to prevalence of AQP4-Ab, long-term visual recovery and the risk of developing to NMO/MS. PMID:27159992

  20. Anti-Hu,Yo antibodies in patients with positive serum AQP4 antibody%水通道蛋白-4抗体阳性患者血清抗Hu、Yo抗体的检测

    Institute of Scientific and Technical Information of China (English)

    龙友明; 单福兰; 解龙昌; 陈梦宇; 郑杨波; 高聪; 杨宁

    2014-01-01

    目的:观察抗 Hu 抗体和抗 Yo 抗体在水通道蛋白‐4(AQP4)抗体阳性患者中的出现情况。方法检测收集80例 AQP4抗体阳性患者,以间接免疫荧光方法检血清抗 Hu 抗体、Yo 抗体,并回顾性分析抗 Hu 抗体、抗 Yo 抗体阳性患者的临床资料及诊断。 AQP4抗体检测:先以转染 AQP4基因的人胚肾293细胞结合血清中的 AQP4抗体,之后采用免疫荧光方法检测;抗 Hu 抗体、抗 Yo 抗体检测:先以猴小脑冰冻切片结合血清中的抗体,之后采用免疫荧光法检测。结果80例患者中,均未检测到抗 Hu 抗体,仅1例 NMO 患者血清抗 Yo 抗体阳性。结论抗 Hu 抗体和抗 Yo 抗体在无肿瘤的 AQP4抗体阳性患者中少见。%Objective To evaluate the positive rates of serum anti‐Hu , and anti‐Yo antibodies in patients with positive serum aquaporin‐4 (AQP4) antibodies .Methods A consecutive cohort of 80 subjects were analyzed retrospectively . First , sera of patients were tested for AQP4 antibodies in an indirect immunofluorescence assay employing HEK‐293 cells transected with recombinant human AQP4 .Second ,anti‐Hu ,and anti‐Yo antibodies were tested with monkey cerebellum substrate by an indirect immunofluorescence assay .Results Eighty patients with positive AQP4 antibodies were confirmed in the present study .Only one of the examined sera was positive for anti‐Yo antibody (1.25% , 1/80 ) and none was positive for anti‐Hu antibodies .This patient suffered from optic neuritis and transverse myelitis , ranging over three vertebral segments on spinal MRI .Conclusions Anti‐Hu and anti‐Yo antibodies were rare in our patients with positive serum AQP4 antibodies .

  1. Electron Crystallography of Aquaporins

    OpenAIRE

    Andrews, Simeon; Reichow, Steve L; Gonen, Tamir

    2008-01-01

    Aquaporins are a family of ubiquitous membrane proteins that form a pore for the permeation of water. Both electron and X-ray crystallography played major roles in determining the atomic structures of a number of aquaporins. This review focuses on electron crystallography, and its contribution to the field of aquaporin biology. We briefly discuss electron crystallography and the two-dimensional crystallization process. We describe features of aquaporins common to both electron and X-ray cryst...

  2. Melanocortin MC4 receptor agonists alleviate brain damage in abdominal compartment syndrome in the rat.

    Science.gov (United States)

    Liu, Dong; Zhang, Hong-Guang; Zhao, Zi-Ai; Chang, Ming-Tao; Li, Yang; Yu, Jian; Zhang, Ye; Zhang, Lian-Yang

    2015-02-01

    Intra-abdominal hypertension (IAH) is accompanied by high morbidity and mortality in surgical departments and ICUs. However, its specific pathophysiology is unclear. IAH not only leads to intra-abdominal tissue damage but also causes dysfunction in distal organs, such as the brain. In this study, we explore the protective effects of melanocortin 4 receptor agonists in IAH-induced brain injury. The IAH rat models were induced by hemorrhagic shock/resuscitation (with the mean arterial pressure (MAP) maintained at 30 mm Hg for 90 min followed by the reinfusion of the withdrawn blood with lactated Ringer's solution). Then, air was injected into the peritoneal cavity of the rats to maintain an intra-abdominal pressure of 20 mm Hg for 4 h. The effects of the melanocortin 4 receptor agonist RO27-3225 in alleviating the rats' IAH brain injuries were observed, which indicated that RO27-3225 could reduce brain edema, the expressions of the IL-1β and TNF-α inflammatory cytokines, the blood-brain barrier's permeability and the aquaporin4 (AQP4) and matrix metalloproteinase 9 (MMP9) levels. Moreover, the nicotinic acetylcholine receptor antagonist chlorisondamine and the selective melanocortin 4 receptor antagonist HS024 can negate the protective effects of the RO27-3225. The MC4R agonist can effectively reduce the intracerebral proinflammatory cytokine gene expression and alleviate the brain injury caused by blood-brain barrier damage following IAH. PMID:25616531

  3. Control of the Aquaporin-4 Channel Water Permeability by Structural Dynamics of Aromatic/Arginine Selectivity Filter Residues.

    Science.gov (United States)

    Kitchen, Philip; Conner, Alex C

    2015-11-17

    The aquaporins (AQPs) make up a family of integral membrane proteins that control cellular water flow. Gating of the water channel by conformational changes induced by phosphorylation or protein-protein interactions is an established regulatory mechanism for AQPs. Recent in silico and crystallographic analyses of the structural biology of AQPs suggest that the rate of water flow can also be controlled by small movements of single-amino acid side chains lining the water pore. Here we use measurements of the membrane water permeability of mammalian cells expressing AQP4 mutants to provide the first in vitro evidence in support of this hypothesis. PMID:26512424

  4. Effects of glycerin fructose combined with dexamethasone on the expressions of aquaporins-4 and matrix metalloproteinases-9 and neurological function in mice after cerebral hemorrhage%甘油果糖联合地塞米松对小鼠脑出血灶周水通道蛋白和基质金属蛋白酶表达及神经功能的影响

    Institute of Scientific and Technical Information of China (English)

    管海博; 寿记新; 马林; 丁攀峰; 贺云; 程森; 高海东; 张帝; 王洛波

    2015-01-01

    Objective To assess the effects of glycerin fructose combined with dexamethasone on neurological function and the expressions of aquaporins (AQP)-4 and matrix metalloproteinases (MMP)-9 in mice after cerebral hemorrhage.Methods Totally 96 male mice(kunming) were randomly divided into the control group (n =24), the model group (n =24), dexamethasone treatment group (n=24), glycerin fructose combined with dexamethasone treatment group (combination group, n=24).The cerebral hemorrhage model was set up in the last three groups, which were given corresponding drug treatment.Mice in each group were subgrouped into 12 h ,1 d, 3 d and 5 d groups according to the time after treatment (n=6, each group).The neurological function was determined according to the reformed mNSS.The dry and wet weight method was used to the brain water content.RT-PCR technology was used to analysis the expressions of AQP-4 and MMP-9 mRNA in mice brain tissue.Results Each treatment group as compared with model group, mNSS was the highest (F=4.56, P<0.05).the brain water content was the lowest (F=5.38, P<0.05), the mRNA expressions of AQP-4 and MMP-9 was the least in combination Group(F=4.02, F=4.68, P <0.05) Conclusions Dexamethasone may relieve cerebral edema, improve the neural function in mice after brain hemorrhage and protect the brain tissue by regulating the transcriptional expression of AQP-4 and MMP-9.If combined with the high permeability dehydrant glycerin fructose,dexamethasone will further inhibit the progress of neurological impairment and brain edema.%目的 评测联合应用甘油果糖和地塞米松对小鼠神经功能损害及出血灶周围组织中水通道蛋白4(AQP-4)、基质金属蛋白酶9(MMP-9)表达的影响. 方法 将96只雄性昆明小鼠,随机分为对照组24只、模型组24只、地塞米松治疗组24只、甘油果糖联合地塞米松治疗组(联合组)24只;后三组建立脑出血模型后,并给予给予相应药物治疗.于造模术后12 h、1

  5. A study on protective effects of epigallocatechin gallate on encephaledema following traumatic brain injury in rats%表没食子儿茶素没食子酸酯对大鼠创伤性脑水肿保护作用的研究

    Institute of Scientific and Technical Information of China (English)

    张铂; 王兵; 曹书华; 王勇强

    2015-01-01

    .82±0.32,SOD(U/mg):107.58±10.87,MDA(nmol/mg):5.61±1.64,AQP4 IHC评分(分):6.92±0.71,GFAP的IHC评分(分):6.71±0.52,AQP4蛋白表达(IA值):1.14±0.06,GFAP蛋白表达(IA值):1.21±0.07,均P<0.01〕;免疫组化法检测EGCG组大鼠AQP4和GFAP的阳性细胞数减少,颜色变浅。结论 EGCG对大鼠创伤性脑损伤继发脑水肿的抑制作用与降低血管通透性、增加SOD水平,降低MDA水平及AQP4和GFAP的表达有关。%Objective To observe the inhibitory effect of epigallocatechin gallate (EGCG) on encephaledema following traumatic brain injury (TBI) in rats and its mechanism.Methods 200 Wistar rats were randomly divided into three groups: sham operation (n= 20), model (n= 90) and EGCG (n= 90) groups. The classic Feeney free fall drop method was used to establish the model of TBI. In EGCG group, intraperitoneal injection of EGCG in normal saline 100 mg/kg (10 mL/kg) was immediately given to the rats after model establishment, and in model group, equal amount of normal saline was administered with the same method, once 24 hours for 2 days in all the groups. At 24, 48, and 72 hours after the administration in various groups, the changes of water content, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in brain tissues were determined, cerebral vascular permeability was evaluated by evans blue (EB) content in the brain tissues, the changes of expressions of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) in brain tissues were determined by immunohistochemical and Western Blot, and the cerebral histopathological changes were observed in various groups.Results Compared with sham operation group, the water content, the vascular permeability and MDA level in brain tissues were significantly higher, while the cerebral SOD activity was significant lower in the model group; the scores of cells with positive AQP4 and GFAP expressions (IHC score) were obviously

  6. Central Role of Maladapted Astrocytic Plasticity in Ischemic Brain Edema Formation.

    Science.gov (United States)

    Wang, Yu-Feng; Parpura, Vladimir

    2016-01-01

    Brain edema formation and the ensuing brain damages are the major cause of high mortality and long term disability following the occurrence of ischemic stroke. In this process, oxygen and glucose deprivation and the resulting reperfusion injury play primary roles. In response to the ischemic insult, the neurovascular unit experiences both intracellular and extracellular edemas, associated with maladapted astrocytic plasticity. The astrocytic plasticity includes both morphological and functional plasticity. The former involves a reactive gliosis and the subsequent glial retraction. It relates to the capacity of astrocytes to buffer changes in extracellular chemical levels, particularly K(+) and glutamate, as well as the integrity of the blood-brain barrier (BBB). The latter involves the expression and activity of a series of ion and water transport proteins. These molecules are grouped together around glial fibrillary acidic protein (GFAP) and water channel protein aquaporin 4 (AQP4) to form functional networks, regulate hydromineral balance across cell membranes and maintain the integrity of the BBB. Intense ischemic challenges can disrupt these capacities of astrocytes and result in their maladaptation. The maladapted astrocytic plasticity in ischemic stroke cannot only disrupt the hydromineral homeostasis across astrocyte membrane and the BBB, but also leads to disorders of the whole neurovascular unit. This review focuses on how the maladapted astrocytic plasticity in ischemic stroke plays the central role in the brain edema formation. PMID:27242440

  7. Aquaporin 4 antibody [NMO Ab] status in patients with severe optic neuritis in India.

    Science.gov (United States)

    Ambika, Selvakumar; Balasubramanian, Mahalakshmi; Theresa, Lily; Veeraputhiran, Akila; Arjundas, Deepak

    2015-12-01

    Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system that causes attacks of optic neuritis and transverse myelitis. The discovery of a specific serum marker for NMO-IgG antibody [aquaporin 4 antibody/AQP4 Ab] has revolutionised the treatment of demyelinating diseases. Severe vision loss can be seen in optic neuritis (ON) associated with both multiple sclerosis (MS) and NMO. Identifying this antibody in optic neuritis patients can help us to establish the likelihood of these patients developing NMO (Jarius et al. Neurol Sci 298:158-162, 2010). It is important to differentiate these two entities as the treatment strategies of MS and NMO are different. To the best of our knowledge, there is no published literature regarding the importance of identifying this antibody in severe optic neuritis in Indian patients. Hence we decided to screen our severe optic neuritis patients for this AQP4 Ab. To investigate the presence of aquaporin 4 antibody and determine its prognostic value for visual and neurological outcome, in patients with bilateral and recurrent [severe] ON without any previous neurological manifestations presenting to a neuro-ophthalmology clinic in India. Single centre, prospective study. 40 patients (27 female patients and 13 male) with severe optic neuritis [patients with no visual improvement by 4 weeks from onset of vision loss] who presented either as recurrent attacks or as bilateral and severe optic neuritis between January 2010 and June 2011 were enrolled. Clinical features, visual outcome and sequential neurological events were compared between the seropositive and the seronegative groups. Aquaporin 4 antibodies were detected from serum using ELISA technique and IIF technique. Presence of this antibody in the serum was considered to be seropositive status and patients who did not have this antibody were considered seronegatives. AQP4 antibodies were detected in 8 of the 40 patients with severe ON (20 %).The

  8. A Single Amino Acid Substitution Prevents Recognition of a Dominant Human Aquaporin-4 Determinant in the Context of HLA-DRB1*03:01 by a Murine TCR

    Science.gov (United States)

    Arellano, Benjamine; Hussain, Rehana; Miller-Little, William A.; Herndon, Emily; Lambracht-Washington, Doris; Eagar, Todd N.; Lewis, Robert; Healey, Don; Vernino, Steven; Greenberg, Benjamin M.; Stüve, Olaf

    2016-01-01

    Background Aquaporin 4 (AQP4) is considered a putative autoantigen in patients with Neuromyelitis optica (NMO), an autoinflammatory disorder of the central nervous system (CNS). HLA haplotype analyses of patients with NMO suggest a positive association with HLA-DRB1* 03:01. We previously showed that the human (h) AQP4 peptide 281–300 is the dominant immunogenic determinant of hAQP4 in the context of HLA-DRB1*03:01. This immunogenic peptide stimulates a strong Th1 and Th17 immune response. AQP4281-300-specific encephalitogenic CD4+ T cells should initiate CNS inflammation that results in a clinical phenotype in HLA-DRB1*03:01 transgenic mice. Methods Controlled study with humanized experimental animals. HLA-DRB1*03:01 transgenic mice were immunized with hAQP4281-300, or whole-length hAQP4 protein emulsified in complete Freund’s adjuvant. Humoral immune responses to both antigens were assessed longitudinally. In vivo T cell frequencies were assessed by tetramer staining. Mice were followed clinically, and the anterior visual pathway was tested by pupillometry. CNS tissue was examined histologically post-mortem. Flow cytometry was utilized for MHC binding assays and to immunophenotype T cells, and T cell frequencies were determined by ELISpot assay. Results Immunization with hAQP4281-300 resulted in an in vivo expansion of antigen-specific CD4+ T cells, and an immunoglobulin isotype switch. HLA-DRB1*03:01 TG mice actively immunized with hAQP4281-300, or with whole-length hAQP4 protein were resistant to developing a neurological disease that resembles NMO. Experimental mice show no histological evidence of CNS inflammation, nor change in pupillary responses. Subsequent analysis reveals that a single amino acid substitution from aspartic acid in hAQP4 to glutamic acid in murine (m)AQP4 at position 290 prevents the recognition of hAQP4281-300 by the murine T cell receptor (TCR). Conclusion Induction of a CNS inflammatory autoimmune disorder by active immunization of

  9. Aquaporins in the adult mouse submandibular and sublingual salivary glands.

    Science.gov (United States)

    Aure, Marit H; Ruus, Ann-Kristin; Galtung, Hilde K

    2014-02-01

    Aquaporins (AQPs) is a family of membrane bound water channels found in most tissues. In addition to contribute to transepithelial water movement, AQPs are shown to be involved in a variety of processes such as proliferation, cell migration, and apoptosis. In salivary glands, it is well known that AQP5 plays an important role in fluid secretion. In recent years, several AQPs that demonstrate specific expression trends during development have been found in the mouse submandibular gland (SMG). In this study, we wanted to further investigate the presence and localization of the AQP family in the adult mouse SMG in addition to the less studied sublingual gland. Real time PCR and Western blot demonstrated the presence of AQP3, 4, 8, 9, and 11 transcripts and proteins. AQP1 and AQP7 were shown to be localized in endothelial cells, while AQP4 was found in the satellite cells of the parasympathetic ganglia in both glands. The result from this study shows that AQPs are found in defined subpopulations of cells in salivary glands, providing novel insights to their specific roles in salivary glands. PMID:23880985

  10. Regulation of the perilymphatic-endolymphatic water shunt in the cochlea by membrane translocation of aquaporin-5.

    Science.gov (United States)

    Eckhard, A; Dos Santos, A; Liu, W; Bassiouni, M; Arnold, H; Gleiser, C; Hirt, B; Harteneck, C; Müller, M; Rask-Andersen, H; Löwenheim, H

    2015-12-01

    Volume homeostasis of the cochlear endolymph depends on radial and longitudinal endolymph movements (LEMs). LEMs measured in vivo have been exclusively recognized under physiologically challenging conditions, such as experimentally induced alterations of perilymph osmolarity or endolymph volume. The regulatory mechanisms that adjust LEMs to the physiological requirements of endolymph volume homeostasis remain unknown. Here, we describe the formation of an aquaporin (AQP)-based "water shunt" during the postnatal development of the mouse cochlea and its regulation by different triggers. The final complementary expression pattern of AQP5 (apical membrane) and AQP4 (basolateral membrane) in outer sulcus cells (OSCs) of the cochlear apex is acquired at the onset of hearing function (postnatal day (p)8-p12). In vitro, hyperosmolar perfusion of the perilymphatic fluid spaces or the administration of the muscarinic agonist pilocarpine in cochlear explants (p14) induced the translocation of AQP5 channel proteins into the apical membranes of OSCs. AQP5 membrane translocation was blocked by the muscarinic antagonist atropine. The muscarinic M3 acetylcholine (ACh) receptor (M3R) was identified in murine OSCs via mRNA expression, immunolabeling, and in vitro binding studies using an M3R-specific fluorescent ligand. Finally, the water shunt elements AQP4, AQP5, and M3R were also demonstrated in OSCs of the human cochlea. The regulation of the AQP4/AQP5 water shunt in OSCs of the cochlear apex provides a molecular basis for regulated endolymphatic volume homeostasis. Moreover, its dysregulation or disruption may have pathophysiologic implications for clinical conditions related to endolymphatic hydrops, such as Ménière's disease. PMID:26208470

  11. Morphology and Aquaporin Immunohistochemistry of the Uterine Tube of Saanen Goats (Capra hircus): Comparison Throughout the Reproductive Cycle.

    Science.gov (United States)

    Arrighi, S; Bosi, G; Frattini, S; Coizet, B; Groppetti, D; Pecile, A

    2016-06-01

    The expression of six different aquaporins (AQP1, 2, 3, 4, 5 and 9), integral membrane water channels that facilitate bi-directional passive movement of water, was investigated by immunohistochemistry in the uterine tube of pre-pubertal and adult Saanen goats (Capra hircus), comparing the different phases of the oestrous cycle. Regional morphology and secretory processes were markedly different during the goat oestrous cycle. The tested AQP molecules showed different expression patterns in comparison with already studied species. AQP1-immunoreactivity was evidenced at the endothelium of blood vessels and in nerve fibres, regardless of the tubal tract and cycle period. AQP4-immunoreactivity was shown on the lateral plasmalemma in the basal third of the epithelial cells at infundibulum and ampulla level in the cycling goats, more evidently during follicular than during luteal phase. No AQP4-immunoreactivity was noticed at the level of the isthmus region, regardless of the cycle phase. AQP5-immunoreactivity, localized at the apical surface of epithelial cells, increased from pre-puberty to adulthood. Thereafter, AQP5-immunoreactivity was prominent during the follicular phase, when it strongly decorated the apical plasmalemma of all epithelial cells at ampullary level. During luteal phase, immunoreactivity was discontinuous, being weak to strong at the apex of the secretory cells protruding into the lumen. In the isthmus region, the strongest AQP5-immunoreactivity was seen during follicular phase, with a clear localization in the apical plasmalemma of all the epithelial cells and also on the lateral plasmalemma. AQP2, 3 and 9 were undetectable all along the goat uterine tube. Likely, a collaboration of different AQP molecules sustains the fluid production in the goat uterine tube. AQP1-mediated transudation from the blood capillaries, together with permeation of the epithelium by AQP4 in the basal rim of the epithelial cells and final intervening of apical AQP5, could

  12. Aquaporin 4-specific T cells and NMO-IgG cause primary retinal damage in experimental NMO/SD.

    Science.gov (United States)

    Zeka, Bleranda; Hastermann, Maria; Kaufmann, Nathalie; Schanda, Kathrin; Pende, Marko; Misu, Tatsuro; Rommer, Paulus; Fujihara, Kazuo; Nakashima, Ichiro; Dahle, Charlotte; Leutmezer, Fritz; Reindl, Markus; Lassmann, Hans; Bradl, Monika

    2016-01-01

    Neuromyelitis optica/spectrum disorder (NMO/SD) is a severe, inflammatory disease of the central nervous system (CNS). In the majority of patients, it is associated with the presence of pathogenic serum autoantibodies (the so-called NMO-IgGs) directed against the water channel aquaporin 4 (AQP4), and with the formation of large, astrocyte-destructive lesions in spinal cord and optic nerves. A large number of recent studies using optical coherence tomography (OCT) demonstrated that damage to optic nerves in NMO/SD is also associated with retinal injury, as evidenced by retinal nerve fiber layer (RNFL) thinning and microcystic inner nuclear layer abnormalities. These studies concluded that retinal injury in NMO/SD patients results from secondary neurodegeneration triggered by optic neuritis.However, the eye also contains cells expressing AQP4, i.e., Müller cells and astrocytes in the retina, epithelial cells of the ciliary body, and epithelial cells of the iris, which raised the question whether the eye can also be a primary target in NMO/SD. Here, we addressed this point in experimental NMO/SD (ENMO) induced in Lewis rat by transfer of AQP4268-285-specific T cells and NMO-IgG.We show that these animals show retinitis and subsequent dysfunction/damage of retinal axons and neurons, and that this pathology occurs independently of the action of NMO-IgG. We further show that in the retinae of ENMO animals Müller cell side branches lose AQP4 reactivity, while retinal astrocytes and Müller cell processes in the RNFL/ganglionic cell layers are spared. These changes only occur in the presence of both AQP4268-285-specific T cells and NMO-IgG.Cumulatively, our data show that damage to retinal cells can be a primary event in NMO/SD. PMID:27503347

  13. 右美托咪定对全脑缺血再灌注大鼠血脑屏障通透性的影响%Effect of dexmedetomidine on permeability of blood-brain barrier in rats subjected to global cerbral ischemia-reperfusion

    Institute of Scientific and Technical Information of China (English)

    郭培培; 严虹; 陈璟莉; 吴会生; 袁世荧

    2013-01-01

    Objective To evaluate the effects of dexmedetomidine on the permeability of blood-brain barrier in rats subjected to global cerebral ischemia-reperfusion (I/R).Methods Thirty-six male Sprague-Dawley rats,weighing 250-300 g,were randomly divided into 3 groups (n =12 each):sham operation group (group S),global cerebral I/R group (group I/R) and dexmedetomidine group (group D).Global cerebral I/R was induced by occlusion of bilateral common carotid arteries combined with hypotension (MAP was maintained at 35-45 mm Hg) in anesthetized rats.In group D,dexmedetomidine was infused at a rate of 3μg· kg-1 · h-1 until 2 h of reperfusion after a loading dose of dexmedetomidine 3 μg/kg was injected intravenously immediately after onset of I/R.The rats were sacrificed at 24 h of reperfusion and their brains were immediately removed for microscopic examination of hippocampal CA1 region and for determination of the cell apoptosis,brain water content,Evans blue content and aquaporin 4 (AQP4) expression.Results The number of apoptotic cells was significantly larger,and brain water content,Evans blue content and AQP4 expression were higher in groups I/R and D than in group S (P < 0.05 or 0.01).The number of apoptotic cells was significantly smaller,and brain water content,and Evans blue content and AQP4 expression were lower in group D than in group I/R (P < 0.05 or 0.01).Global cerebral I/R-induced pathological changes were significantly attenuated in group D.Conclusion Dexmedetomidine can decrease the permeability of blood-brain barrier and attenuate global cerebral I/R injury in rats,and down-regulation of AQP4 expression may be involved in the mechanism.%目的 评价右美托咪定对全脑缺血再灌注大鼠血脑屏障通透性的影响.方法 成年雄性SD大鼠36只,体重250 ~ 300 g,采用随机数字表法,将其分为3组(n=12):假手术组(S组)、全脑缺血再灌注组(I/R组)和右美托咪定组(D组).采用夹闭双侧颈总动脉联合低血压法

  14. Increased neuronal and astroglial aquaporin-1 immunoreactivity in rat striatum by chemical preconditioning with 3-nitropropionic acid.

    Science.gov (United States)

    Hoshi, Akihiko; Tsunoda, Ayako; Yamamoto, Teiji; Tada, Mari; Kakita, Akiyoshi; Ugawa, Yoshikazu

    2016-07-28

    Aquaporin-1 (AQP1) is a water channel expressed in the choroid plexus and participates in forming cerebrospinal fluid. Interestingly, reactive astrocytes also express AQP1 in the central nervous system under some pathological conditions. On the other hand, 3-nitropropionic acid (3NP) is a mitochondrial toxin that causes selective degeneration of striatum; however, its chemical preconditioning is neuroprotective against cerebral ischemia. We previously reported that mild 3NP application is accompanied with numerous reactive astrocytes in rat striatum devoid of typical necrotic lesions. Therefore, we studied whether AQP1 in the rat striatum could be upregulated with reactive astrocytosis using the 3NP model. Immunohistochemical or immunofluorescence analysis showed that reactive astrocytosis in the striatum, which upregulates glial fibrillary acidic protein and glutamine synthetase, was induced by mild doses of 3NP administration. Intriguingly, after 3NP treatment, AQP1 was intensely expressed not only by the subpopulation of astroglia but also by neurons. The AQP1 immunoreactivity became more intensified at the early-subtoxic stage (ES: 24-48h), but not as much in the delayed-subtoxic stage (DS: 96-120h). In contrast, AQP4 expression in the striatum was downregulated after 3NP treatment, in particular during the ES stage. AQP1 upregulation/AQP4 downregulation induced under subtoxic 3NP treatment may play a pivotal role in water homeostasis and cell viability in the striatum. PMID:27181510

  15. Aquaporin Tetramer Composition Modifies the Function of Tobacco Aquaporins*

    OpenAIRE

    Otto, Beate; Uehlein, Norbert; Sdorra, Sven; Fischer, Matthias; Ayaz, Muhammad; Belastegui-Macadam, Xana; Heckwolf, Marlies; Lachnit, Magdalena; Pede, Nadine; Priem, Nadine; Reinhard, André; Siegfart, Sven; Urban, Michael; Kaldenhoff, Ralf

    2010-01-01

    Heterologous expression in yeast cells revealed that NtAQP1, a member of the so-called PIP1 aquaporin subfamily, did not display increased water transport activity in comparison with controls. Instead, an increased CO2-triggered intracellular acidification was observed. NtPIP2;1, which belongs to the PIP2 subfamily of plant aquaporins, behaved as a true aquaporin but lacked a CO2-related function. Results from split YFP experiments, protein chromatography, and gel electrophoresis indicated th...

  16. Expression of aquaporin-9 in the brain tissue of rats with infectious brain edema%AQP-9在大鼠感染性脑水肿脑组织中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    田培超; 王怀立; 罗强; 禚志红

    2008-01-01

    Objective To investigate the expression of aquaporin-9(AQP-9)in the brain tissue of rats with infectious brain edema and explore the role of AQP-9 in the oecurrgnce and progression of the brain edema. Methods A total of 128 normal 1-month-old SD rats weighing 70-100 g of either sex were randomly divided into two equal groups, namely the normal saline(NS) group and lipopolysaecharide(LPS)group.Acute infectious brain edema was induced in rats in the LPS group by injecting LPS via the left internal carotid artery,and the rats in the NS groups received NS injection.At 6,12,24 and 48 h after the injection,the brain tissue was taken from the rats to observe the histopathology by Hernatoxylin-Eosin Stain and lneasure the brain water content(BWC).The permeability of the blood-brain barrier of the rats was tested using Evans blue(EB)method.The expressions of AQP-9 protein and mRNA in the brain tissue Were detected using immunohistochemistry and RT-PCR,respectively. Results InLPS group,the space around the blood vessels was obviously broadened in the brain tissue,where inflammatory cell infiltration,glioeyte swelling,vacuolar degeneration of the neurons and neuronal nuclear shrinkage were seen.At 6,12,24,and 48 h following LPS or NS injection,the BWC,EB content,and expressions of AQP-9 protein and mRNA in the LPS group were all significantly higher than those in the NS group(P<0.05),In the LPS group,positive correlations were found between BWC and EB content,AQP-9 protein expression and BWC,AQP一9 mRNA and BWC,AQP-9mR.NA and EBcontent,and between AQP-9 protein andmRNA.Conclusion AQP-9 might participate in occurrcnce and development of infectious brain edema in rats,it might be positive correlation.%目的 探讨水通道蛋白-9(AQP-9)在内毒素脂多糖(LPS)致大鼠感染性脑水肿脑组织中的表达及意义. 方法 1月龄普通级SD大鼠128只采用随机数字表法分为生理盐水(NS)组(64只)和LPS组(64只),采用颈内动脉注射LPS制作大鼠感染

  17. Aquaporins as potential drug targets

    Institute of Scientific and Technical Information of China (English)

    Fang WANG; Xue-chao FENG; Yong-ming LI; Hong YANG; Tong-hui MA

    2006-01-01

    The aquaporins (AQP) are a family of integral membrane proteins that selectively transport water and,in some cases,small neutral solutes such as glycerol and urea.Thirteen mammalian AQP have been molecularly identified and localized to various epithelial,endothelial and other tissues.Phenotype studies of transgenic mouse models of AQP knockout,mutation,and in some cases humans with AQP mutations have demonstrated essential roles for AQP in mammalian physiology and pathophysiology,including urinary concentrating function,exocrine glandular fluid secretion,brain edema formation,regulation of intracranial and intraocular pressure,skin hydration,fat metabolism,tumor angiogenesis and cell migration.These studies suggest that AQP may be potential drug targets for not only new diuretic reagents for various forms of pathological water retention,but also targets for novel therapy of brain edema,inflammatory disease,glaucoma,obesity,and cancer.However,potent AQP modulators for in vivo application remain to be discovered.

  18. Aquaporin-4 gene silencing protects injured neurons after early cerebral infarction

    Directory of Open Access Journals (Sweden)

    Zhan-ping He

    2015-01-01

    Full Text Available Aquaporin-4 regulates water molecule channels and is important in tissue regulation and water transportation in the brain. Upregulation of aquaporin-4 expression is closely related to cellular edema after early cerebral infarction. Cellular edema and aquaporin-4 expression can be determined by measuring cerebral infarct area and apparent diffusion coefficient using diffusion-weighted imaging (DWI. We examined the effects of silencing aquaporin-4 on cerebral infarction. Rat models of cerebral infarction were established by occlusion of the right middle cerebral artery and siRNA-aquaporin-4 was immediately injected via the right basal ganglia. In control animals, the area of high signal intensity and relative apparent diffusion coefficient value on T2-weighted imaging (T2WI and DWI gradually increased within 0.5-6 hours after cerebral infarction. After aquaporin-4 gene silencing, the area of high signal intensity on T2WI and DWI reduced, relative apparent diffusion coefficient value was increased, and cellular edema was obviously alleviated. At 6 hours after cerebral infarction, the apparent diffusion coefficient value was similar between treatment and model groups, but angioedema was still obvious in the treatment group. These results indicate that aquaporin-4 gene silencing can effectively relieve cellular edema after early cerebral infarction; and when conducted accurately and on time, the diffusion coefficient value and the area of high signal intensity on T2WI and DWI can reflect therapeutic effects of aquaporin-4 gene silencing on cellular edema.

  19. Loss of Perivascular Aquaporin 4 and Inwardly Rectifying Potassium Channel 4.1 in Human Mesial Temporal Lobe Epilepsy%人颞叶内侧癫痫海马组织星形胶质细胞水通道蛋白4和内向整流性钾离子通道4.1的再分布

    Institute of Scientific and Technical Information of China (English)

    徐仟; 孙振荣; 李桂林; 孙异临; 杨少华; 袁芳

    2012-01-01

    目的 研究人颞叶内侧癫痫海马组织星形胶质细胞水通道蛋白4(AQP4)和内向整流性钾离子通道4.1(Kir4.1) 的分布.方法 对10 例颞叶内侧癫痫(MTLE)和6 例非颞叶内侧癫痫(non-MTLE)手术切除海马组织,应用光镜及透射电镜观察组织学及超微结构,免疫荧光组织化学法观察星形胶质细胞AQP4 和Kir4.1 的分布.结果 MTLE 海马组织星形胶质细胞大量增生伴明显肿胀,神经元显著固缩.non-MTLE 海马组织中,AQP4 和Kir4.1 在星形胶质细胞血管周围足突(pAST-ef)分布多于其他部位,呈现极性分布特点;而在MTLE 海马组织中,AQP4 和Kir4.1 在pAST-ef 分布减少,其他部位分布增加,极性分布改变.结论 海马组织星形胶质细胞上AQP4 和Kir4.1 极性分布变化可能与颞叶内侧癫痫发生相关.%Objective To investigate the distribution of aquaporin 4 (AQP4) and inwardly rectifying potassium channel 4.1 (Kir4.1) in the astrocytes from human mesial temporal lobe epilepsy (MTLE). Methods Hippocampal specimens, including 10 cases of MTLE and 6 cases of non-MTLE, were observed under optical and transmission electron microscopy. The distribution of AQP4 and Kir4.1 in astrocytes was investigated with immunoflurescence. Results Compared with non-MTLE hippocampus, the main structural changes of MTLE included remarkable hyperplasia astrocytes, serious swelling astrocytes and distinguished astrophy neurons. In non-MTLE hippocampus, immunoflurescence signals of AQP4 and Kir4.1 were enriched along perivascular astrocyte end-feet domain. However, it reveals significant loss of AQP4 and Kir4.1 in perivascular astrocyte end-feet domain in MTLE. Conclusion Loss of perivascular AQP4 and Kir4.1 in the human MTLE may help to understand the roles of astrocyte in MTLE.

  20. Aquaporin 1 - a novel player in spinal cord injury.

    Science.gov (United States)

    Nesic, O; Lee, J; Unabia, G C; Johnson, K; Ye, Z; Vergara, L; Hulsebosch, C E; Perez-Polo, J R

    2008-05-01

    The role of water channel aquaporin 1 (AQP-1) in uninjured or injured spinal cords is unknown. AQP-1 is weakly expressed in neurons and gray matter astrocytes, and more so in white matter astrocytes in uninjured spinal cords, a novel finding. As reported before, AQP-1 is also present in ependymal cells, but most abundantly in small diameter sensory fibers of the dorsal horn. Rat contusion spinal cord injury (SCI) induced persistent and significant four- to eightfold increases in AQP-1 levels at the site of injury (T10) persisting up to 11 months post-contusion, a novel finding. Delayed AQP-1 increases were also found in cervical and lumbar segments, suggesting the spreading of AQP-1 changes over time after SCI. Given that the antioxidant melatonin significantly decreased SCI-induced AQP-1 increases and that hypoxia inducible factor-1alpha was increased in acutely and chronically injured spinal cords, we propose that chronic hypoxia contributes to persistent AQP-1 increases after SCI. Interestingly; AQP-1 levels were not affected by long-lasting hypertonicity that significantly increased astrocytic AQP-4, suggesting that the primary role of AQP-1 is not regulating isotonicity in spinal cords. Based on our results we propose possible novel roles for AQP-1 in the injured spinal cords: (i) in neuronal and astrocytic swelling, as AQP-1 was increased in all surviving neurons and reactive astrocytes after SCI and (ii) in the development of the neuropathic pain after SCI. We have shown that decreased AQP-1 in melatonin-treated SCI rats correlated with decreased AQP-1 immunolabeling in the dorsal horns sensory afferents, and with significantly decreased mechanical allodynia, suggesting a possible link between AQP-1 and chronic neuropathic pain after SCI. PMID:18248364

  1. Detecting aquaporin function and regulation

    Science.gov (United States)

    Madeira, Ana; Moura, Teresa; Soveral, Graça

    2016-02-01

    Water is the major component of cells and tissues throughout all forms of life. Fluxes of water and solutes through cell membranes and epithelia are essential for osmoregulation and energy homeostasis. Aquaporins are membrane channels expressed in almost every organism and involved in the bidirectional transfer of water and small solutes across cell membranes. Aquaporins have important biological roles and have been implicated in several pathophysiological conditions suggesting a great translational potential in aquaporin-based diagnostic and therapeutics. Detecting aquaporin function is critical for assessing regulation and screening for new activity modulators that can prompt the development of efficient medicines. Appropriate methods for functional analysis comprising suitable cell models and techniques to accurately evaluate water and solute membrane permeability are essential to validate aquaporin function and assess short-term regulation. The present review describes established assays commonly used to assess aquaporin function in cells and tissues, as well as the experimental biophysical strategies required to reveal functional regulation and identify modulators, the first step for aquaporin drug discovery.

  2. Ammonia and urea permeability of mammalian aquaporins

    DEFF Research Database (Denmark)

    Litman, Thomas; Søgaard, Rikke; Zeuthen, Thomas

    2009-01-01

    /arginine region, and an exclusively water-permeable aquaporin can be transformed into an ammonia-permeable aquaporin by single point mutations in this region. The ammonia-permeable aquaporins fall into two groups: those that are permeable (AQP3, 7, 9, 10) and those that are impermeable (AQP8) to glycerol. The two......The human aquaporins,AQP3,AQP7, AQP8,AQP9, and possibly AQP10, are permeable to ammonia, and AQP7, AQP9, and possibly AQP3, are permeable to urea. In humans, these aquaporins supplement the ammonia transport of the Rhesus (Rh) proteins and the urea transporters (UTs). The mechanism by which...... significant at alkaline pH. It is debated whether the H(+) ion passes via the aquaporin or by some external route; the investigation of this problem requires the aquaporin-expressing cell to be voltage-clamped. The ammonia-permeable aquaporins differ from other aquaporins by having a less restrictive aromatic...

  3. Aquaporin tetramer composition modifies the function of tobacco aquaporins.

    Science.gov (United States)

    Otto, Beate; Uehlein, Norbert; Sdorra, Sven; Fischer, Matthias; Ayaz, Muhammad; Belastegui-Macadam, Xana; Heckwolf, Marlies; Lachnit, Magdalena; Pede, Nadine; Priem, Nadine; Reinhard, André; Siegfart, Sven; Urban, Michael; Kaldenhoff, Ralf

    2010-10-01

    Heterologous expression in yeast cells revealed that NtAQP1, a member of the so-called PIP1 aquaporin subfamily, did not display increased water transport activity in comparison with controls. Instead, an increased CO(2)-triggered intracellular acidification was observed. NtPIP2;1, which belongs to the PIP2 subfamily of plant aquaporins, behaved as a true aquaporin but lacked a CO(2)-related function. Results from split YFP experiments, protein chromatography, and gel electrophoresis indicated that the proteins form heterotetramers when coexpressed in yeast. Tetramer composition had effects on transport activity as demonstrated by analysis of artificial heterotetramers with a defined proportion of NtAQP1 to NtPIP2;1. A single NtPIP2;1 aquaporin in a tetramer was sufficient to significantly increase the water permeability of the respective yeast cells. With regard to CO(2)-triggered intracellular acidification, a cooperative effect was observed, where maximum rates were measured when the tetramer consisted of NtAQP1 aquaporins only. The results confirm the model of an aquaporin monomer as a functional unit for water transport and suggest that, for CO(2)-related transport processes, a structure built up by the tetramer is the basis of this function. PMID:20657033

  4. Epigallocatechin-3-Gallate (EGCG) Attenuates Traumatic Brain Injury by Inhibition of Edema Formation and Oxidative Stress.

    Science.gov (United States)

    Zhang, Bo; Wang, Bing; Cao, Shuhua; Wang, Yongqiang

    2015-11-01

    Traumatic brain injury (TBI) is a major cause of mortality and long-term disability, which can decrease quality of life. In spite of numerous studies suggesting that Epigallocatechin-3-gallate (EGCG) has been used as a therapeutic agent for a broad range of disorders, the effect of EGCG on TBI remains unknown. In this study, a weight drop model was established to evaluate the therapeutic potential of EGCG on TBI. Rats were administered with 100 mg/kg EGCG or PBS intraperitoneally. At different times following trauma, rats were sacrificed for analysis. It was found that EGCG (100 mg/kg, i.p.) treatment significantly reduced brain water content and vascular permeability at 12, 24, 48, 72 hour after TBI. Real-time PCR results revealed that EGCG inhibited TBI-induced IL-1β and TNF-α mRNA expression. Importantly, CD68 mRNA expression decreasing in the brain suggested that EGCG inhibited microglia activation. Western blotting and immunohistochemistry results showed that administering of EGCG significantly inhibited the levels of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression. TBI-induced oxidative stress was remarkably impaired by EGCG treatment, which elevated the activities of SOD and GSH-PX. Conversely, EGCG significantly reduced the contents of MDA after TBI. In addition, EGCG decreased TBI-induced NADPH oxidase activation through inhibition of p47(phox) translocation from cytoplasm to plasma membrane. These data demonstrate that EGCG treatment may be an effective therapeutic strategy for TBI and the underlying mechanism involves inhibition of oxidative stress. PMID:26557015

  5. Osmotic water transport in aquaporins

    DEFF Research Database (Denmark)

    Zeuthen, Thomas; Alsterfjord, Magnus; Beitz, Eric;

    2013-01-01

    molecules give rise to no water transport. Accordingly, the rate of water transport is proportional to the reflection coefficient σ, while the solute permeability, P(S), is proportional to 1 - σ. The model was tested in aquaporins heterologously expressed in Xenopus oocytes. A variety of aquaporin channel...... sizes and geometries were obtained with the two aquaporins AQP1 and AQP9 and mutant versions of these. Osmotic water transport was generated by adding 20 mM of a range of different-sized osmolytes to the outer solution. The osmotic water permeability and the reflection coefficient were measured......Abstract  We test a novel, stochastic model of osmotic water transport in aquaporins. A solute molecule present at the pore mouth can either be reflected or permeate the pore. We assume that only reflected solute molecules induce osmotic transport of water through the pore, while permeating solute...

  6. Erythropoietin modulation of astrocyte water permeability as a component of neuroprotection

    OpenAIRE

    Gunnarson, Eli; Song, Yutong; Kowalewski, Jacob M.; Brismar, Hjalmar; Brines, Michael; Cerami, Anthony; Andersson, Ulf; Zelenina, Marina; Aperia, Anita

    2009-01-01

    Disturbed brain water homeostasis with swelling of astroglial cells is a common complication in stroke, trauma, and meningitis and is considered to be a major cause of permanent brain damage. Astroglial cells possess the water channel aquaporin 4 (AQP4). Recent studies from our laboratory have shown that glutamate, acting on group I metabotropic glutamate receptors (mGluRs), increases the permeability of astrocyte AQP4, which, in situations of hypoxia-ischemia, will increase astrocyte water u...

  7. What are aquaporins for?

    Science.gov (United States)

    Hill, A E; Shachar-Hill, B; Shachar-Hill, Y

    2004-01-01

    The prime function of aquaporins (AQPs) is generally believed to be that of increasing water flow rates across membranes by raising their osmotic or hydraulic permeability. In addition, this applies to other small solutes of physiological importance. Notable applications of this 'simple permeability hypothesis' (SPH) have been epithelial fluid transport in animals, water exchanges associated with transpiration, growth and stress in plants, and osmoregulation in microbes. We first analyze the need for such increased permeabilities and conclude that in a range of situations at the cellular, subcellular and tissue levels the SPH cannot satisfactorily account for the presence of AQPs. The analysis includes an examination of the effects of the genetic elimination or reduction of AQPs (knockouts, antisense transgenics and null mutants). These either have no effect, or a partial effect that is difficult to explain, and we argue that they do not support the hypothesis beyond showing that AQPs are involved in the process under examination. We assume that since AQPs are ubiquitous, they must have an important function and suggest that this is the detection of osmotic and turgor pressure gradients. A mechanistic model is proposed--in terms of monomer structure and changes in the tetrameric configuration of AQPs in the membrane--for how AQPs might function as sensors. Sensors then signal within the cell to control diverse processes, probably as part of feedback loops. Finally, we examine how AQPs as sensors may serve animal, plant and microbial cells and show that this sensor hypothesis can provide an explanation of many basic processes in which AQPs are already implicated. Aquaporins are molecules in search of a function; osmotic and turgor sensors are functions in search of a molecule. PMID:15014915

  8. 中枢神经脱髓鞘疾病血清水通道蛋白4抗体检测的临床意义%Seroprevalence and diagnostic value of aquaporin-4 antibody in patients with inflammatory central nervous system demyelinating diseases

    Institute of Scientific and Technical Information of China (English)

    武雷; 杨扬; 黄德晖; 吴卫平

    2011-01-01

    Objective To assess the seroprevalence and diagnostic value of aquaporin-4 antibody (AQP4-Ab) in patients with inflammatory central nervous system demyelinating diseases. Methods Seventy-two patients with neuromyelitis optica (NMO), 68 with multiple sclerosis (MS), 4 with optic neuritis (ON), and 41 with transverse myelitis (TM) were included in this study. The TM group comprised 19 patients with non-longitudinally extensive transverse myelitis (nLETM), 14 with monophasic longitudinally extensive transverse myelitis (mLETM), and 8 with recurrent longitudinally extensive transverse myelitis (rLETM). The serum levels of AQP4-Ab was detected by indirect immunofluorence assay in these patients. Results AQP4-Ab was detected in 72.2% (52/72) patients with NMO, 5.9% (4/ 68) patients with MS, 25.0% (1/4) patients with ON, and 17.1% (7/41) patients with TM, showing a significant difference in the positivity between NMO and MS groups (P<0.01). AQP4-Ab seropositivity rate was 5.3% (1/19) in nLETM patients, 62.5% (5/8) in rLETM patients and 7.1% (1/14) in mLETM patients, significantly higher in rLETM than in nLETM (P<0.01) and mLETM groups (P<0.05), but no statistical difference was found between rLETM and NMO groups. Conclusions A high seroprevalence of AQP4-Ab is observed in patients with NMO and rLETM, which support the hypothesis that NMO and rLETM belong to NMO spectrum disorders. AQP4-Ab can serve as a useful index for diagnosing NMO and differential diagnosis from MS. More attention and effective immunosuppressive treatments should be given to patients positive for AQP4-Ab.%目的 研究中枢神经脱髓鞘疾病患者血清水通道蛋白4抗体(AQP4-Ab)阳性率,并探讨其临床意义.方法 采集2008年11月至2010年10月间就诊于我院神经内科门诊和病房的185例中枢神经系统脱髓鞘疾病患者血清,其中视神经脊髓炎(NMO)72例,多发性硬化(MS)68例,视神经炎(ON)4例,横贯性脊髓炎(TM)41例;后者包括非长

  9. *602974 AQUAPORIN 7; AQP7 [OMIM

    Lifescience Database Archive (English)

    Full Text Available FIELD NO 602974 FIELD TI 602974 AQUAPORIN 7; AQP7 ;;AQUAPORIN 7-LIKE; AQP7L;; AQUAPORIN, ADIPOSE ... in humans. In their study of an obesity cohort (17 lean , 22 nonseverely obese, and 13 severely obese) and ... a type 2 diabetes cohort (17 lean ... and 39 obese), they found that severely obese wome ...

  10. Expression, Distribution and Role of Aquaporin Water Channels in Human and Animal Stomach and Intestines

    Directory of Open Access Journals (Sweden)

    Cui Zhu

    2016-08-01

    Full Text Available Stomach and intestines are involved in the secretion of gastrointestinal fluids and the absorption of nutrients and fluids, which ensure normal gut functions. Aquaporin water channels (AQPs represent a major transcellular route for water transport in the gastrointestinal tract. Until now, at least 11 AQPs (AQP1–11 have been found to be present in the stomach, small and large intestines. These AQPs are distributed in different cell types in the stomach and intestines, including gastric epithelial cells, gastric glands cells, absorptive epithelial cells (enterocytes, goblet cells and Paneth cells. AQP1 is abundantly distributed in the endothelial cells of the gastrointestinal tract. AQP3 and AQP4 are mainly distributed in the basolateral membrane of epithelial cells in the stomach and intestines. AQP7, AQP8, AQP10 and AQP11 are distributed in the apical of enterocytes in the small and large intestines. Although AQP-null mice displayed almost no phenotypes in gastrointestinal tracts, the alterations of the expression and localization of these AQPs have been shown to be associated with the pathology of gastrointestinal disorders, which suggests that AQPs play important roles serving as potential therapeutic targets. Therefore, this review provides an overview of the expression, localization and distribution of AQPs in the stomach, small and large intestine of human and animals. Furthermore, this review emphasizes the potential roles of AQPs in the physiology and pathophysiology of stomach and intestines.

  11. Aquaporin expression and localization in the rabbit eye.

    Science.gov (United States)

    Bogner, Barbara; Schroedl, Falk; Trost, Andrea; Kaser-Eichberger, Alexandra; Runge, Christian; Strohmaier, Clemens; Motloch, Karolina A; Bruckner, Daniela; Hauser-Kronberger, Cornelia; Bauer, Hans Christian; Reitsamer, Herbert A

    2016-06-01

    Aquaporins (AQPs) are important for ocular homeostasis and function. While AQP expression has been investigated in ocular tissues of human, mouse, rat and dog, comprehensive data in rabbits are missing. As rabbits are frequently used model organisms in ophthalmic research, the aim of this study was to analyze mRNA expression and to localize AQPs in the rabbit eye. The results were compared with the data published for other species. In cross sections of New Zealand White rabbit eyes AQP0 to AQP5 were labeled by immunohistology and analyzed by confocal microscopy. Immunohistological findings were compared to mRNA expression levels, which were analyzed by quantitative reverse transcription real time polymerase chain reaction (qRT-PCR). The primers used were homologous against conserved regions of AQPs. In the rabbit eye, AQP0 protein expression was restricted to the lens, while AQP1 was present in the cornea, the chamber angle, the iris, the ciliary body, the retina and, to a lower extent, in optic nerve vessels. AQP3 and AQP5 showed immunopositivity in the cornea. AQP3 was also present in the conjunctiva, which could not be confirmed for AQP5. However, at a low level AQP5 was also traceable in the lens. AQP4 protein was detected in the ciliary non-pigmented epithelium (NPE), the retina, optic nerve astrocytes and extraocular muscle fibers. For most tissues the qRT-PCR data confirmed the immunohistology results and vice versa. Although species differences exist, the AQP protein expression pattern in the rabbit eye shows that, especially in the anterior section, the AQP distribution is very similar to human, mouse, rat and dog. Depending on the ocular regions investigated in rabbit, different protein and mRNA expression results were obtained. This might be caused by complex gene regulatory mechanisms, post-translational protein modifications or technical limitations. However, in conclusion the data suggest that the rabbit is a useful in-vivo model to study AQP function

  12. Two-dimensional crystal structure of aquaporin-4 bound to the inhibitor acetazolamide.

    Science.gov (United States)

    Kamegawa, Akiko; Hiroaki, Yoko; Tani, Kazutoshi; Fujiyoshi, Yoshinori

    2016-04-01

    Acetazolamide (AZA) reduces the water permeability of aquaporin-4, the predominant water channel in the brain. We determined the structure of aquaporin-4 in the presence of AZA using electron crystallography. Most of the features of the 5-Å density map were consistent with those of the previously determined atomic model. The map showed a protruding density from near the extracellular pore entrance, which most likely represents the bound AZA. Molecular docking simulations supported the location of the protrusion as the likely AZA-binding site. These findings suggest that AZA reduces water conduction by obstructing the pathway at the extracellular entrance without inducing a large conformational change in the protein. PMID:26908838

  13. Robust High Performance Aquaporin based Biomimetic Membranes

    DEFF Research Database (Denmark)

    Helix Nielsen, Claus; Zhao, Yichun; Qiu, C.;

    2013-01-01

    Aquaporins are water channel proteins with high water permeability and solute rejection, which makes them promising for preparing high-performance biomimetic membranes. Despite the growing interest in aquaporin-based biomimetic membranes (ABMs), it is challenging to produce robust and defect...... on top of a support membrane. Control membranes, either without aquaporins or with the inactive AqpZ R189A mutant aquaporin served as controls. The separation performance of the membranes was evaluated by cross-flow forward osmosis (FO) and reverse osmosis (RO) tests. In RO the ABM achieved a water......% rejection for urea and a water permeability around 10 L/(m2h) with 2M NaCl as draw solution. Our results demonstrate the feasibility of using aquaporin proteins in biomimetic membranes for technological applications....

  14. Elevated cAMP increases aquaporin-3 plasma membrane diffusion

    DEFF Research Database (Denmark)

    Marlar, Saw; Christensen, Eva Arnspang; Koffman, Jennifer Skaarup;

    2014-01-01

    exits via basolateral AQP3 and AQP4. Upon long-term stimulation with AVP or during thirst, expression levels of both AQP2 and AQP3 are increased; however, there is so far no evidence for short-term AVP regulation of AQP3 or AQP4. To facilitate the increase in transepithelial water transport, AQP3 may be.......05)]. Immunoelectron microscopy showed no obvious difference in AQP3-EGFP expression levels or localization in the plasma membrane upon forskolin stimulation. Thus AQP3-EGFP diffusion is altered upon increased cAMP, which may correspond to basolateral adaptations in response to the increased apical water readsorption...

  15. Serum anti-aquaporin 4 antibody in neuromyelitis patients is not correlated with the length of injured spinal cord segments

    Institute of Scientific and Technical Information of China (English)

    Shirong Li; Lan Chu; Shuai Dong; Hui Yu; Zhu Xu; Hao Wang

    2011-01-01

    Clinical information and serum samples of 20 neuromyelitis patients and 30 patients with multiple sclerosis were collected in this study. The expression of anti-aquaporin 4 antibody in the serum of all patients was detected with an indirect immunofluorescence assay, using human embryonic kidney 293 cell line that stably express human-derived aquaporin 4 as a substrate. The characteristics of head and spinal magnetic resonance imaging were also observed in patients who had neuromyelitis and were positive for anti-aquaporin 4 antibody. Results showed that the expression of anti-aquaporin 4 antibody was significantly different between multiple sclerosis patients and neuromyelitis patients. There were 13 out of 20 neuromyelitis patients (including high-risk syndrome) that were positive for anti-aquaporin 4 antibody. The magnetic resonance imaging examinations of the head and spinal cord found that among the 13 positive patients, nine cases showed normal cerebral hemisphere and optic nerve, two cases had optic nerve changes, and one case had an atypical lesion in the brain. All 30 multiple sclerosis patients were negative for this antibody. The experimental findings indicate that patients with neuromyelitis optica had more than three lesioned segments in the spinal cord by magnetic resonance imaging, and the segment length of the injured spinal cord was not associated with the titer of aquaporin 4 antibody in neuromyelitis patients.

  16. Desalination by biomimetic aquaporin membranes: Review of status and prospects

    DEFF Research Database (Denmark)

    Tang, C.Y.; Zhao, Y.; Wang, R.;

    2013-01-01

    Based on their unique combination of offering high water permeability and high solute rejection aquaporin proteins have attracted considerable interest over the last years as functional building blocks of biomimetic membranes for water desalination and reuse. The purpose of this review......; including an overview of our own recent developments in aquaporin-based membranes. Finally we outline future prospects of aquaporin based biomimetic membrane for desalination and water reuse....... is to provide an overview of the properties of aquaporins, their preparation and characterization. We discuss the challenges in exploiting the remarkable properties of aquaporin proteins for membrane separation processes and we present various attempts to construct aquaporin in membranes for desalination...

  17. Treatment of neuromyelitis optica: state-of-the-art and emerging therapies.

    Science.gov (United States)

    Papadopoulos, Marios C; Bennett, Jeffrey L; Verkman, Alan S

    2014-09-01

    Neuromyelitis optica (NMO) is an autoimmune disease of the CNS that is characterized by inflammatory demyelinating lesions in the spinal cord and optic nerve, potentially leading to paralysis and blindness. NMO can usually be distinguished from multiple sclerosis (MS) on the basis of seropositivity for IgG antibodies against the astrocytic water channel aquaporin-4 (AQP4). Differentiation from MS is crucial, because some MS treatments can exacerbate NMO. NMO pathogenesis involves AQP4-IgG antibody binding to astrocytic AQP4, which causes complement-dependent cytotoxicity and secondary inflammation with granulocyte and macrophage infiltration, blood-brain barrier disruption and oligodendrocyte injury. Current NMO treatments include general immunosuppressive agents, B-cell depletion, and plasma exchange. Therapeutic strategies targeting complement proteins, the IL-6 receptor, neutrophils, eosinophils and CD19--all initially developed for other indications--are under clinical evaluation for repurposing for NMO. Therapies in the preclinical phase include AQP4-blocking antibodies and AQP4-IgG enzymatic inactivation. Additional, albeit currently theoretical, treatment options include reduction of AQP4 expression, disruption of AQP4 orthogonal arrays, enhancement of complement inhibitor expression, restoration of the blood-brain barrier, and induction of immune tolerance. Despite the many therapeutic options in NMO, no controlled clinical trials in patients with this condition have been conducted to date. PMID:25112508

  18. Biomimetic aquaporin membranes coming of age

    DEFF Research Database (Denmark)

    Tang, Chuyang; Wang, Zhining; Petrinić, Irena;

    2015-01-01

    Membrane processes have been widely used for water purification because of their high stability, efficiency, low energy requirement and ease of operation. Traditional desalting membranes are mostly dense polymeric films with a "trade off" effect between permeability and selectivity. Biological...... membranes, on the other hand, can perform transport in some cases with exceptional flux and rejection properties. In particular the discovery of selective water channel proteins - aquaporins - has prompted interest in using these proteins as building blocks for new types of membranes. The major challenge...... in developing an aquaporin-based membrane technology stems from the fact that the aquaporin protein spans a membrane only a few nanometers thick. Such ultrathin membranes will not be able to withstand any substantial pressures, nor being industrially scalable without supporting structures. Incorporating...

  19. Projection map of aquaporin-9 at 7 A resolution.

    Science.gov (United States)

    Viadiu, Hector; Gonen, Tamir; Walz, Thomas

    2007-03-16

    Aquaporin-9, an aquaglyceroporin present in diverse tissues, is unique among aquaporins because it is not only permeable to water, urea and glycerol, but also allows passage of larger uncharged solutes. Single particle analysis of negatively stained recombinant rat aquaporin-9 revealed a particle size characteristic of the tetrameric organization of all members of the aquaporin family. Reconstitution of aquaporin-9 into two-dimensional crystals enabled us to calculate a projection map at 7 A resolution. The projection structure indicates a tetrameric structure, similar to GlpF, with each square-like monomer forming a pore. A comparison of the pore-lining residues between the crystal structure of GlpF and a homology model of aquaporin-9 locates substitutions in these residues predominantly to the hydrophobic edge of the tripathic pore of GlpF, providing first insights into the structural basis for the broader substrate specificity of aquaporin-9. PMID:17239399

  20. Identification and role of plasma membrane aquaporin in maize root

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Using antiserum against expressed aquaporin fusion protein, GST-RD28, the distribution of aquaporin in the plasma membrane of maize root protoplasts has been examined under confocal laser scanning microscopy by indirect fluorescence staining. Results indicate that there are abundant aquaporins in maize roots, which are distributed in plasma membrane unevenly. Western blotting analysis of total protein solubilized from maize root plasma membrane shows that antiserum against GST-RD28 can cross-react with one protein around 55 ku. Another 28 ku protein can also be detected when the concentration of SDS and DTT in SDS-PAGE sample buffer is increased. The 55 and 28 ku proteins may be dimeric and monomeric of aquaporin respectively. Functional experiments show that aquaporin blocker HgCl2 and aquaporin antiserum can suppress the swelling of maize root protoplasts in hypotonic solution, indicating that aquaporin in plasma membrane of protoplast facilitates rapid transmembrane water flow.

  1. Aquaporin, forward osmosis and biomimetic membranes.

    Science.gov (United States)

    Kocherginsky, Nikolai

    2013-12-01

    Aquaporin attracted attention not only of physiologists and biophysicists, but also of chemical engineers. Here we critically analyze a paper describing aquaporin-based artificial membranes, suggested for forward osmosis-based water purification (Wang et al. 2012, Small 8, pp. 1185-1190). Related papers published later by the same group are also discussed. We indicate recently developed general approach to describe membrane transport, membrane permeability and selectivity, which is applicable for forward osmosis. In addition, we also mention our papers describing simple nitrocellulose-based membranes, which have selective aqueous channels without proteins, but successfully imitate many properties of biomembranes. PMID:24434310

  2. Renal Aquaporins in Health and Disease

    DEFF Research Database (Denmark)

    Kortenoeven, Marleen L.A.; Olesen, Emma Tina Bisgaard; Fenton, Robert A.

    Aquaporins (AQPs) are a large family of membrane proteins that act as semipermeable channels. The majority of AQPs are permeable to water, but a subset of the family can also transport glycerol, urea, and other small solutes. Currently, 13 AQP homologues have been identified in mammals, termed AQP0...

  3. Brain

    Science.gov (United States)

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  4. Aquaporins in Salivary Glands: From Basic Research to Clinical Applications

    Directory of Open Access Journals (Sweden)

    Christine Delporte

    2016-01-01

    Full Text Available Salivary glands are involved in saliva secretion that ensures proper oral health. Aquaporins are expressed in salivary glands and play a major role in saliva secretion. This review will provide an overview of the salivary gland morphology and physiology of saliva secretion, and focus on the expression, subcellular localization and role of aquaporins under physiological and pathophysiological conditions, as well as clinical applications involving aquaporins. This review is highlighting expression and localization of aquaporins in human, rat and mouse, the most studied species and is pointing out possible difference between major salivary glands, i.e., parotid, submandibular and sublingual glands.

  5. Aquaporins in Urinary Extracellular Vesicles (Exosomes)

    OpenAIRE

    Sayaka Oshikawa; Hiroko Sonoda; Masahiro Ikeda

    2016-01-01

    Since the successful characterization of urinary extracellular vesicles (uEVs) by Knepper’s group in 2004, these vesicles have been a focus of intense basic and translational research worldwide, with the aim of developing novel biomarkers and therapeutics for renal disease. Along with these studies, there is growing evidence that aquaporins (AQPs), water channel proteins, in uEVs have the potential to be diagnostically useful. In this review, we highlight current knowledge of AQPs in uEVs fro...

  6. 水通道蛋白的表达与关节炎关系的研究进展%Research progress on the relationship between expressions of aquaporins and arthritis

    Institute of Scientific and Technical Information of China (English)

    冯芳芳; 于超; 谭春江; 陈文列; 陈赛楠

    2015-01-01

    Aquaporins ( AQPs ) act as an important channel for body water crossing the cell membrane, and are closely related to the balance of water metabolism and water reserves. Recent studies have found that there are signiifcant differences in the expressions of AQPs in arthritis joints and normal joints. The expressions of AQP1, AQP3 and AQP9 in the patients with rheumatoid arthritis and osteoarthritis are all signiifcantly increased, which are enhanced with the occurrence of lesions. The expressions of AQP4 are higher in the patients with gouty arthritis and osteoarthritis than in the patients with normal joints, which can reflect the severity of articular diseases. After medication, the expressions of AQPs are remarkably reduced, and the arthritis symptoms are improved. It points out that a special intimate relationship exists between the upregulation of the expressions of AQPs in arthritis joints and the occurrence and development of pathological changes. With AQPs as therapeutic targets, the cell membrane permeability to water can be reduced through regulation, so as to improve inlfammation. It offers a new research idea for the prevention and control of arthritis. In this paper, the studies on the relationship between AQPs and arthritis in recent years are reviewed.

  7. Aquaporins in Urinary Extracellular Vesicles (Exosomes)

    Science.gov (United States)

    Oshikawa, Sayaka; Sonoda, Hiroko; Ikeda, Masahiro

    2016-01-01

    Since the successful characterization of urinary extracellular vesicles (uEVs) by Knepper’s group in 2004, these vesicles have been a focus of intense basic and translational research worldwide, with the aim of developing novel biomarkers and therapeutics for renal disease. Along with these studies, there is growing evidence that aquaporins (AQPs), water channel proteins, in uEVs have the potential to be diagnostically useful. In this review, we highlight current knowledge of AQPs in uEVs from their discovery to clinical application. PMID:27322253

  8. Aquaporins in Urinary Extracellular Vesicles (Exosomes).

    Science.gov (United States)

    Oshikawa, Sayaka; Sonoda, Hiroko; Ikeda, Masahiro

    2016-01-01

    Since the successful characterization of urinary extracellular vesicles (uEVs) by Knepper's group in 2004, these vesicles have been a focus of intense basic and translational research worldwide, with the aim of developing novel biomarkers and therapeutics for renal disease. Along with these studies, there is growing evidence that aquaporins (AQPs), water channel proteins, in uEVs have the potential to be diagnostically useful. In this review, we highlight current knowledge of AQPs in uEVs from their discovery to clinical application. PMID:27322253

  9. Aquaporin-1 Expressed in Cultured Human Trabecular Meshwork Cells

    Institute of Scientific and Technical Information of China (English)

    Mingkai Lin; Jian Ge; Yehong Zhuo; Yuqing Lan; Keming Yu; Jianliang Zheng

    2002-01-01

    Objective:To determine if aquaporin-1 could be detected in cultures of human trabecularshwork cells. Methods: Using primers specific for aquaporin-1, reverse transcription combined withpolymerase chain reaction (RT-PCR) yielded a product and its size with total RNAprepared from the human trabecular meshwork cells. SDS-PAGE and immunoblottingwere also used in this study to detect the specific water channel.Results: The presence of this product and its size (298 base pairs) are consistent withthat of an aquaporin-1 message in these cells. A band of 28 kD in agreement with themolecular size of aquaporin-1 was showed in a film by immunoblotting.Conclusion: The presence of aquaporin-1 in human trabecular meshwork cells, thepredominant cell-type of the primary outflow region of the human eye, suggests that waterchannels may be involved in the movement of aqueous fluid out of the eye. In addition,the existence of aquaporin-1 on cultures of human trabecular meshwork cells provides anin vitro model to study the endogenous expression of aquaporin-1 and its possible role inthe regulation of aqueous outflow.

  10. 胰岛素对大鼠局灶性脑缺血后脑水肿及水通道蛋白9的影响%Effects of Insulin on Expression of Aquaporin -9 and Brain Edema after Focal Cerebral Is-chemia in Rats

    Institute of Scientific and Technical Information of China (English)

    李珊珊; 陈忠云; 李婧; 徐志伟; 杨旭

    2015-01-01

    Objective: To observe the effects of insulin on expression of Aquaporin-9 (AQP-9) and brain edema after middle cerebral artery occlusion (MCAO) in rats. Methods: One hundred and eighty SD rats were randomly divided into groups of sham, MCAO and insulin treatment, with 30 rats in each group. Six rats in each group were observed at 6 h, 12 h, 24 h, 48 h, 72 h after MCAO. The MCAO models were estabilish by suture method, and the sham group without suture. The insulin treatment group was given insulin by intraperitoneal injection. The nerve function, blood-brain barrier permeability, brain water content and AQP-9 mRNA expression were evaluated. Results: The brain water content, blood-brain barrier permeability and AQP-9 mRNA expression of groups MCAO and insulin began to increase at 6 h and reached peak at 48 h and gradually decreased at 72 h, which were signifi-cantly higher than those in sham group (P<0.05). Compared with the MCAO group, the brain water content, blood-brain barrier permeability and AQP-9 mRNA expression in insulin treatment group were obviously decreased (P<0.05). There were a significantly passive correlation between AQP-9 mRNA expression and brain water contents, blood-brain barrier permeability(r=0.905, P<0.01; r=0.923, P<0.01). Conclusion: Insulin can reduce brain edema through suppressing expression of AQP-9 in cerebral ischemia in rats.%目的:观察胰岛素对大脑中动脉栓塞(MCAO)大鼠模型脑水肿形成及水通道蛋白-9(AQP-9)表达的影响。方法:SD 大鼠180只,随机分为假手术组、模型组、胰岛素组各30只,分别在栓塞后6、12、24、48、72 h 观察6只。线栓法制备 MCAO 模型,假手术组不插入线栓,胰岛素组 MCAO 后立即给予腹腔注射胰岛素干预。各组进行神经功能评分,检测血脑屏障通透性、脑含水量和脑组织 AQP-9 mRNA 表达。结果:模型组和胰岛素组于缺血6 h 后,脑含水量、血脑屏障通透性及 AQP-9 mRNA

  11. Polyphenols as Modulators of Aquaporin Family in Health and Disease

    Directory of Open Access Journals (Sweden)

    Diana Fiorentini

    2015-01-01

    Full Text Available Polyphenols are bioactive molecules widely distributed in fruits, vegetables, cereals, and beverages. Polyphenols in food sources are extensively studied for their role in the maintenance of human health and in the protection against development of chronic/degenerative diseases. Polyphenols act mainly as antioxidant molecules, protecting cell constituents against oxidative damage. The enormous number of polyphenolic compounds leads to huge different mechanisms of action not fully understood. Recently, some evidence is emerging about the role of polyphenols, such as curcumin, pinocembrin, resveratrol, and quercetin, in modulating the activity of some aquaporin (AQP isoforms. AQPs are integral, small hydrophobic water channel proteins, extensively expressed in many organs and tissues, whose major function is to facilitate the transport of water or glycerol over cell plasma membranes. Here we summarize AQP physiological functions and report emerging evidence on the implication of these proteins in a number of pathophysiological processes. In particular, this review offers an overview about the role of AQPs in brain, eye, skin diseases, and metabolic syndrome, focusing on the ability of polyphenols to modulate AQP expression. This original analysis can contribute to elucidating some peculiar effects exerted by polyphenols and can lead to the development of an innovative potential preventive/therapeutic strategy.

  12. Challenges and achievements in the therapeutic modulation of aquaporin functionality.

    Science.gov (United States)

    Beitz, Eric; Golldack, André; Rothert, Monja; von Bülow, Julia

    2015-11-01

    Aquaporin (AQP) water and solute channels have basic physiological functions throughout the human body. AQP-facilitated water permeability across cell membranes is required for rapid reabsorption of water from pre-urine in the kidneys and for sustained near isosmolar water fluxes e.g. in the brain, eyes, inner ear, and lungs. Cellular water permeability is further connected to cell motility. AQPs of the aquaglyceroporin subfamily are necessary for lipid degradation in adipocytes and glycerol uptake into the liver, as well as for skin moistening. Modulation of AQP function is desirable in several pathophysiological situations, such as nephrogenic diabetes insipidus, Sjögren's syndrome, Menière's disease, heart failure, or tumors to name a few. Attempts to design or to find effective small molecule AQP inhibitors have yielded only a few hits. Challenges reside in the high copy number of AQP proteins in the cell membranes, and spatial restrictions in the protein structure. This review gives an overview on selected physiological and pathophysiological conditions in which modulation of AQP functions appears beneficial and discusses first achievements in the search of drug-like AQP inhibitors. PMID:26277280

  13. Compartmentalization of Aquaporins in the Human Intestine

    Directory of Open Access Journals (Sweden)

    Rajendram V. Rajnarayanan

    2008-06-01

    Full Text Available Improper localization of water channel proteins called aquaporins (AQP induce mucosal injury which is implicated in Crohn’s disease and ulcerative colitis. The amino acid sequences of AQP3 and AQP10 are 79% similar and belong to the mammalian aquaglyceroporin subfamily. AQP10 is localized on the apical compartment of the intestinal epithelium called the glycocalyx while AQP3 is selectively targeted to the basolateral membrane. Despite the high sequence similarity and evolutionary relatedness, the molecular mechanism involved in the polarity, selective targeting and function of AQP3 and AQP10 in the intestine is largely unknown. Our hypothesis is that the differential polarity and selective targeting of AQP3 and AQP10 in the intestinal epithelial cells is influenced by amino acid signal motifs. We performed sequence and structural alignments to determine differences in signals for localization and posttranslational glycosylation. The basolateral sorting motif “YRLL” is present in AQP3 but absent in AQP10; while Nglycosylation signals are present in AQP10 but absent in AQP3. Furthermore, the C-terminal region of AQP3 is longer compared to AQP10. The sequence and structural differences between AQP3 and AQP10 provide insights into the differential compartmentalization and function of these two aquaporins commonly expressed in human intestines.

  14. Variations of brain edema and neurological function of rat models of cerebral infarction after hyperbaric oxygen therapy%高压氧干预脑梗死模型大鼠脑水肿及神经功能变化

    Institute of Scientific and Technical Information of China (English)

    田烜

    2015-01-01

    背景:研究认为,高压氧有较好保护脑神经和脑细胞的作用,应用高压氧可使氧分压快速弥撒到相对缺氧的脑组织中,增加脑组织的血氧含量,促进脑水肿及脑神经功能的恢复。目的:观察大脑中动脉阻塞造模后高压氧干预对大鼠脑梗死组织水肿的影响,并探讨其对脑梗死大鼠神经功能保护的可能作用机制。方法:成年雌性SD大鼠65只,造模成功60只,随机区组法分为假手术组、脑梗死组、高压氧组,每组20只,按照线栓线法建立大鼠大脑中动脉阻塞脑梗死模型。造模后3 d,通过TUNEL法检测各实验组大鼠脑梗死区神经细胞的凋亡情况。伤后72 h通过RT-PCR、Western blot检测脑梗死区周围AQP4/9、基质金属蛋白酶9/2基因转录和蛋白的表达,通过苏木精-伊红染色观察脑梗死区病理组织形态学变化,通过免疫组织化学法检测胶质纤维酸性蛋白的表达量,高压氧干预后24 h,3 d及伤后1、2周行Longa行为学评分,检测神经功能的损伤情况。结果与结论:①高压氧组Longa行为学评分在治疗后1,2 d均较脑梗死组显著降低(P <0.05)。②造模后3 d高压氧组细胞凋亡指数均明显低于脑梗死组(P<0.05)。③造模后72 h,与脑梗死组相比高压氧组AQP4/9、基质金属蛋白酶9/2基因和蛋白表达均较显著降低(P<0.05)。结果提示高压氧治疗通过减少大鼠脑梗死区神经细胞的凋亡和降低脑组织水肿,对脑梗死起到保护作用。%BACKGROUND:Several studies have suggested that hyperbaric oxygen could better protect cranial nerve and brain cels. Hyperbaric oxygen therapy can make oxygen partial pressure rapidly diffusing toward relatively hypoxic brain tissue, so as to increase blood oxygen content in the brain tissue, reduce brain edema and promote the recovery of brain function. OBJECTIVE: To observe the effects of hyperbaric oxygen therapy on brain tissue

  15. Expression of aquaporin8 in human astrocytomas: Correlation with pathologic grade

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Shu-juan; Wang, Ke-jian; Gan, Sheng-wei; Xu, Jin; Xu, Shi-ye; Sun, Shan-quan, E-mail: sunsq2151@cqmu.edu.cn

    2013-10-11

    Highlights: •AQP8 is mainly distributed in the cytoplasm of human astrocytoma cells. •AQP8 over-expressed in human astrocytomas, especially glioblastoma. •The up-regulation of AQP8 is related to the pathological grade of human astrocytomas. •AQP8 may contribute to the growth and proliferation of astrocytomas. -- Abstract: Aquaporin8 (AQP8), a member of the aquaporin (AQP) protein family, is weakly distributed in mammalian brains. Previous studies on AQP8 have focused mainly on the digestive and the reproductive systems. AQP8 has a pivotal role in keeping the fluid and electrolyte balance. In this study, we investigated the expression changes of AQP8 in 75 cases of human brain astrocytic tumors using immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction. The results demonstrated that AQP8 was mainly distributed in the cytoplasm of astrocytoma cells. The expression levels and immunoreactive score of AQP8 protein and mRNA increased in low-grade astrocytomas, and further increased in high-grade astrocytomas, especially in glioblastoma. Therefore, AQP8 may contribute to the proliferation of astrocytomas, and may be a biomarker and candidate therapy target for patients with astrocytomas.

  16. Molecular dynamics insights into human aquaporin 2 water channel.

    Science.gov (United States)

    Binesh, A R; Kamali, R

    2015-12-01

    In this study, the first molecular dynamics simulation of the human aquaporin 2 is performed and for a better understanding of the aquaporin 2 permeability performance, the characteristics of water transport in this protein channel and key biophysical parameters of AQP2 tetramer including osmotic and diffusive permeability constants and the pore radius are investigated. For this purpose, recently recovered high resolution X-ray crystal structure of` the human aquaporin 2 is used to perform twenty nanosecond molecular dynamics simulation of fully hydrated tetramer of this protein embedded in a lipid bilayer. The resulting water permeability characteristics of this protein channel showed that the water permeability of the human AQP2 is in a mean range in comparison with other human aquaporins family. Finally, the results reported in this research demonstrate that molecular dynamics simulation of human AQP2 provided useful insights into the mechanisms of water permeation and urine concentration in the human kidney. PMID:26489820

  17. Crystal Structure of an Ammonia-Permeable Aquaporin.

    OpenAIRE

    Kirscht, Andreas; Kaptan, Shreyas S.; Bienert, Gerd Patrick; Chaumont, François; Nissen, Poul; de Groot, Bert L.; Kjellbom, Per; Gourdon, Pontus; Johanson, Urban

    2016-01-01

    Aquaporins of the TIP subfamily (Tonoplast Intrinsic Proteins) have been suggested to facilitate permeation of water and ammonia across the vacuolar membrane of plants, allowing the vacuole to efficiently sequester ammonium ions and counteract cytosolic fluctuations of ammonia. Here, we report the structure determined at 1.18 Å resolution from twinned crystals of Arabidopsis thaliana aquaporin AtTIP2;1 and confirm water and ammonia permeability of the purified protein reconstituted in proteol...

  18. Aquaporins with anion/monocarboxylate permeability: mechanisms, relevance for pathogen-host interactions

    Directory of Open Access Journals (Sweden)

    Janis eRambow

    2014-09-01

    Full Text Available Classically, aquaporins are divided based on pore selectivity into water specific, orthodox aquaporins and solute-facilitating aquaglyceroporins, which conduct e.g. glycerol and urea. However, more aquaporin-passing substrates have been identified over the years, such as the gases ammonia and carbon dioxide or the water-related hydrogen peroxide, and it became apparent that not all aquaporins clearly fit into one of only two subfamilies. Furthermore, certain aquaporins from both major subfamilies have been reported to conduct inorganic anions, such as chloride, or monoacids/monocarboxylates, such as lactic acid/lactate. Here, we summarize the findings on aquaporin anion transport, analyze the pore layout of such aquaporins in comparison to prototypical non-selective anion channels, monocarboxylate transporters, and formate-nitrite transporters, and discuss in which scenarios anion conducting aquaporins may be of physiological relevance.

  19. Neuromyelitis optica spectrum disorder (NMOSD): A new concept.

    Science.gov (United States)

    de Sèze, J; Kremer, L; Collongues, N

    2016-01-01

    The relationship between neuromyelitis optica (NMO) and multiple sclerosis (MS) has long been controversial. NMO was previously considered a form of MS involving predominantly the spinal cord and optic nerve. However, since the discovery of NMO-IgG/aquaporin-4 (AQP4) antibody, an NMO-specific autoantibody to AQP4, some unique clinical features, and magnetic resonance imaging (MRI) and other laboratory findings in NMO, have been further clarified. AQP4 antibody is now the most important laboratory finding for the diagnosis of NMO. Besides typical NMO, some patients with recurrent optic neuritis or recurrent longitudinally extensive transverse myelitis alone are also often positive for AQP4 antibody. Moreover, studies of AQP4 antibody-positive patients have revealed that brain and brainstem lesions are not uncommon in NMO, and some patterns appear to be unique to NMO. All these findings have expanded the NMO concept into 'NMO spectrum disorder' (NMOSD), and new criteria have recently been published. A new antigenic target, myelin oligodendrocyte glycoprotein (MOG), has also been discovered recently. This new antibody seems to correspond to around 20% of seronegative patients, but its specificity needs to be evaluated more precisely, especially in pediatric populations. These recent findings may also have therapeutic impact, as it has been demonstrated that many MS drugs can exacerbate NMO. This report provides an overview of the clinical and neuroimaging features of NMOSD, followed by its treatment. PMID:27157418

  20. Recombinant Production of Human Aquaporin-1 to an Exceptional High Membrane Density in Saccharomyces Cerevisiae

    DEFF Research Database (Denmark)

    Bomholt, Julie; Helix Nielsen, Claus; Scharff-Poulsen, Peter;

    2014-01-01

    cerevisiae was exploited as a host for heterologous expression of human aquaporins. Aquaporin cDNA was expressed from a galactose inducible promoter situated on a plasmid with an adjustable copy number. Human aquaporin was C-terminally tagged with yeast-enhanced GFP to quantify functional expression...

  1. Aquaporin-1 in the choroid plexuses of developing mammalian brain

    DEFF Research Database (Denmark)

    Johansson, P.A.; Dziegielewska, K.M.; Ek, C.J.;

    2005-01-01

    Cerebrospinal fluid, Cerebral ventricles, Blood-CSF barrier, Water transport, Fetus, Human, Rat (Sprague Dawley)......Cerebrospinal fluid, Cerebral ventricles, Blood-CSF barrier, Water transport, Fetus, Human, Rat (Sprague Dawley)...

  2. Expression Analysis of Sugarcane Aquaporin Genes under Water Deficit

    Directory of Open Access Journals (Sweden)

    Manassés Daniel da Silva

    2013-01-01

    Full Text Available The present work is a pioneer study specifically addressing the aquaporin transcripts in sugarcane transcriptomes. Representatives of the four aquaporin subfamilies (PIP, TIP, SIP, and NIP, already described for higher plants, were identified. Forty-two distinct aquaporin isoforms were expressed in four HT-SuperSAGE libraries from sugarcane roots of drought-tolerant and -sensitive genotypes, respectively. At least 10 different potential aquaporin isoform targets and their respective unitags were considered to be promising for future studies and especially for the development of molecular markers for plant breeding. From those 10 isoforms, four (SoPIP2-4, SoPIP2-6, OsPIP2-4, and SsPIP1-1 showed distinct responses towards drought, with divergent expressions between the bulks from tolerant and sensitive genotypes, when they were compared under normal and stress conditions. Two targets (SsPIP1-1 and SoPIP1-3/PIP1-4 were selected for validation via RT-qPCR and their expression patterns as detected by HT-SuperSAGE were confirmed. The employed validation strategy revealed that different genotypes share the same tolerant or sensitive phenotype, respectively, but may use different routes for stress acclimation, indicating the aquaporin transcription in sugarcane to be potentially genotype-specific.

  3. Role of Aquaporin 0 in lens biomechanics.

    Science.gov (United States)

    Sindhu Kumari, S; Gupta, Neha; Shiels, Alan; FitzGerald, Paul G; Menon, Anil G; Mathias, Richard T; Varadaraj, Kulandaiappan

    2015-07-10

    Maintenance of proper biomechanics of the eye lens is important for its structural integrity and for the process of accommodation to focus near and far objects. Several studies have shown that specialized cytoskeletal systems such as the beaded filament (BF) and spectrin-actin networks contribute to mammalian lens biomechanics; mutations or deletion in these proteins alters lens biomechanics. Aquaporin 0 (AQP0), which constitutes ∼45% of the total membrane proteins of lens fiber cells, has been shown to function as a water channel and a structural cell-to-cell adhesion (CTCA) protein. Our recent ex vivo study on AQP0 knockout (AQP0 KO) mouse lenses showed the CTCA function of AQP0 could be crucial for establishing the refractive index gradient. However, biomechanical studies on the role of AQP0 are lacking. The present investigation used wild type (WT), AQP5 KO (AQP5(-/-)), AQP0 KO (heterozygous KO: AQP0(+/-); homozygous KO: AQP0(-/-); all in C57BL/6J) and WT-FVB/N mouse lenses to learn more about the role of fiber cell AQPs in lens biomechanics. Electron microscopic images exhibited decreases in lens fiber cell compaction and increases in extracellular space due to deletion of even one allele of AQP0. Biomechanical assay revealed that loss of one or both alleles of AQP0 caused a significant reduction in the compressive load-bearing capacity of the lenses compared to WT lenses. Conversely, loss of AQP5 did not alter the lens load-bearing ability. Compressive load-bearing at the suture area of AQP0(+/-) lenses showed easy separation while WT lens suture remained intact. These data from KO mouse lenses in conjunction with previous studies on lens-specific BF proteins (CP49 and filensin) suggest that AQP0 and BF proteins could act co-operatively in establishing normal lens biomechanics. We hypothesize that AQP0, with its prolific expression at the fiber cell membrane, could provide anchorage for cytoskeletal structures like BFs and together they help to confer

  4. Role of Aquaporin 0 in lens biomechanics

    International Nuclear Information System (INIS)

    Maintenance of proper biomechanics of the eye lens is important for its structural integrity and for the process of accommodation to focus near and far objects. Several studies have shown that specialized cytoskeletal systems such as the beaded filament (BF) and spectrin-actin networks contribute to mammalian lens biomechanics; mutations or deletion in these proteins alters lens biomechanics. Aquaporin 0 (AQP0), which constitutes ∼45% of the total membrane proteins of lens fiber cells, has been shown to function as a water channel and a structural cell-to-cell adhesion (CTCA) protein. Our recent ex vivo study on AQP0 knockout (AQP0 KO) mouse lenses showed the CTCA function of AQP0 could be crucial for establishing the refractive index gradient. However, biomechanical studies on the role of AQP0 are lacking. The present investigation used wild type (WT), AQP5 KO (AQP5−/−), AQP0 KO (heterozygous KO: AQP0+/−; homozygous KO: AQP0−/−; all in C57BL/6J) and WT-FVB/N mouse lenses to learn more about the role of fiber cell AQPs in lens biomechanics. Electron microscopic images exhibited decreases in lens fiber cell compaction and increases in extracellular space due to deletion of even one allele of AQP0. Biomechanical assay revealed that loss of one or both alleles of AQP0 caused a significant reduction in the compressive load-bearing capacity of the lenses compared to WT lenses. Conversely, loss of AQP5 did not alter the lens load-bearing ability. Compressive load-bearing at the suture area of AQP0+/− lenses showed easy separation while WT lens suture remained intact. These data from KO mouse lenses in conjunction with previous studies on lens-specific BF proteins (CP49 and filensin) suggest that AQP0 and BF proteins could act co-operatively in establishing normal lens biomechanics. We hypothesize that AQP0, with its prolific expression at the fiber cell membrane, could provide anchorage for cytoskeletal structures like BFs and together they help to confer

  5. Crystal Structure of an Ammonia-Permeable Aquaporin

    DEFF Research Database (Denmark)

    Kirscht, Andreas; Kaptan, Shreyas S; Bienert, Gerd Patrick;

    2016-01-01

    the structure determined at 1.18 Å resolution from twinned crystals of Arabidopsis thaliana aquaporin AtTIP2;1 and confirm water and ammonia permeability of the purified protein reconstituted in proteoliposomes as further substantiated by molecular dynamics simulations. The structure of AtTIP2;1 reveals......Aquaporins of the TIP subfamily (Tonoplast Intrinsic Proteins) have been suggested to facilitate permeation of water and ammonia across the vacuolar membrane of plants, allowing the vacuole to efficiently sequester ammonium ions and counteract cytosolic fluctuations of ammonia. Here, we report...... filter region are sufficient to convert a strictly water-specific human aquaporin into an AtTIP2;1-like ammonia channel. A flexible histidine and a novel water-filled side pore are speculated to deprotonate ammonium ions, thereby possibly increasing permeation of ammonia. The molecular understanding...

  6. Aquaporins: Their role in gastrointestinal malignancies.

    Science.gov (United States)

    Nagaraju, Ganji Purnachandra; Basha, Riyaz; Rajitha, Balney; Alese, Olatunji Boladale; Alam, Afroz; Pattnaik, Subasini; El-Rayes, Bassel

    2016-04-01

    Aquaporins (AQPs) are small (~30 kDa monomers) integral membrane water transport proteins that allow water to flow through cell membranes in reaction to osmotic gradients in cells. In mammals, the family of AQPs has thirteen (AQP0-12) unique members that mediate critical biological functions. Since AQPs can impact cell proliferation, migration and angiogenesis, their role in various human cancers is well established. Recently, AQPs have been explored as potential diagnostic and therapeutic targets in gastrointestinal (GI) cancers. GI cancers encompass multiple sites including the colon, esophagus, stomach and pancreas. Research in the last three decades has revealed biological aspects and signaling pathways critical for the development of GI cancers. Since the majority of these cancers are very aggressive and rapidly metastasizes, identifying effective targets is crucial for treatment. Preclinical studies have utilized inhibitors of specific AQPs and knock down of AQP expression using siRNA. Although several studies have explored the role of AQPs in colorectal, esophageal, gastric, hepatocellular and pancreatic cancers, there is no comprehensive review compiling the available information on GI cancers as has been published for other malignancies such as ovarian cancer. Due to the similarities and association of various sites of GI cancers, it is helpful to consider these results collectively in order to better understand the role of specific AQPs in critical GI cancers. This review summarizes the current knowledge of the role of AQPs in GI malignancies with particular focus on diagnosis and therapeutic applications. PMID:26780474

  7. Aquaporins: Their role in cholestatic liver disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This review focuses on currant knowledge on hepato-cyte aquaporins (AQPs) and their significance in bile formation and cholestasis. Canalicular bile secretion results from a combined interaction of several solute transporters and AQP water channels that facilitate wa-ter flow in response to the osmotic gradients created. During choleresis, hepatocytes rapidly increase their canalicular membrane water permeability by modulat-ing the abundance of AQP8. The question was raised as to whether the opposite process, i.e. a decreased canalicular AQP8 expression would contribute to the development of cholestasis. Studies in several experi-mental models of cholestasis, such as extrahepatic obstructive cholestasis, estrogen-induced cholestasis, and sepsis-induced cholestasis demonstrated that the protein expression of hepatocyte AQP8 was impaired. In addition, biophysical studies in canalicular plasma membranes revealed decreased water permeability as-sociated with AQP8 protein downregulation. The com-bined alteration in hepatocyte solute transporters and AQP8 would hamper the efficient coupling of osmotic gradients and canalicular water flow. Thus cholestasis may result from a mutual occurrence of impaired sol-ute transport and decreased water permeability.

  8. Effects of different resuscitation fluids on pulmonary expression of aquaporin1 and aquaporin5 in a rat model of uncontrolled hemorrhagic shock and infection.

    Directory of Open Access Journals (Sweden)

    Ju Gao

    Full Text Available BACKGROUND: To investigate the effects of fluids resuscitation on pulmonary expression of aquaporin1 and aquaporin5 in a rat model of uncontrolled hemorrhagic shock and infection. METHODS: Sixty Sprague-Dawley rats were randomly assigned to five groups, sham operation group (Group C and four treated groups: no fluid resuscitation group (Group NF, groups resuscitated with Lactated Ringer's (LR,7.5% NaCl (HTS and Hydroxyl ethyl starch (HES respectively. Three-phased uncontrolled hemorrhagic shock and infection model was used. Phase I: Massive hemorrhage with a mean arterial pressure of 35-40 mmHg for 60 min, and followed by infection of lipopolysaccharide. Then some animals were resuscitated with solutions mentioned above, until 90 min. Phase II: At hemorrhagic shock 90 minutes, phase II of 60 minutes began with hemostasis and returning of all the initial shed blood. Phase III: Observation phase for 3.5 hours. After phase III, arterial blood gas analysis and the survival rates of the rats were recorded, Wet-to-dry lung weight ratio, BALF protein, pulmonary permeability index, and expressions of aquaporin1 and aquaporin5 were tested. RESULTS: The expressions of aquaporin1 and aquaporin5 were decreased in treatment groups comparing with sham operation group. Group HES and Group HTS decreased pulmonary vascular permeability and Wet-to-dry lung weight ratio, improved arterial blood gas analysis and survival rates, and attenuated the decreased pulmonary expression of aquaporin1 and aquaporin5 after the "two-hit", comparing with groups NF and LR,but these beneficial effects were blunted in group HTS. CONCLUSION: The expression of aquaporin1 and aquaporin5 may play important roles in formation of pulmonary edema. Resuscitation with HTS and HES, especially HES can reduce lung injury after hemorrhagic shock, partly by up-regulating the expressions of aquaporin1 and aquaporin5.

  9. Detection of anti-aquaporin-4 autoantibodies in the sera of Chinese neuromyelitis optica patients

    Institute of Scientific and Technical Information of China (English)

    Miao Li; Weiheng Su; Jie Wang; Francesco Pisani; Antonio Frigeri; Tonghui Ma

    2013-01-01

    In this study, we recruited 10 neuromyelitis optica patients, two multiple sclerosis patients and two myelitis patients. Chinese hamster lung fibroblast (V79) cells transfected with a human aquaporin-4-mCherry fusion protein gene were used to detect anti-aquaporin-4 antibody in neuromyelitis optica patient sera by immunofluorescence. Anti-aquaporin-4 autoantibody was stably detected by immunofluorescence in neuromyelitis optica patient sera exclusively. The sensitivity of the assay for neuromyelitis optica was 90% and the specificity for neuromyelitis optica was 100%. The anti-aquaporin-4 antibody titers in sera were tested with serial dilutions until the signal disappeared. A positive correlation was detected between Expanded Disability Status Scale scores and serum anti-aquaporin-4 antibody titers. The anti-aquaporin-4 antibody assay is highly sensitive and specific in the sera of Chinese neuromyelitis optica patients. Detection of aquaporin-4 autoantibody is important for the diagnosis and treatment of neuromyelitis optica.

  10. Role of Aquaporin 0 in lens biomechanics

    Energy Technology Data Exchange (ETDEWEB)

    Sindhu Kumari, S.; Gupta, Neha [Physiology and Biophysics, Stony Brook University, Stony Brook, NY (United States); Shiels, Alan [Washington University School of Medicine, St. Louis, MO (United States); FitzGerald, Paul G. [Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, CA (United States); Menon, Anil G. [University of Cincinnati College of Medicine, Cincinnati, OH (United States); Mathias, Richard T. [Physiology and Biophysics, Stony Brook University, Stony Brook, NY (United States); SUNY Eye Institute, NY (United States); Varadaraj, Kulandaiappan, E-mail: kulandaiappan.varadaraj@stonybrook.edu [Physiology and Biophysics, Stony Brook University, Stony Brook, NY (United States); SUNY Eye Institute, NY (United States)

    2015-07-10

    Maintenance of proper biomechanics of the eye lens is important for its structural integrity and for the process of accommodation to focus near and far objects. Several studies have shown that specialized cytoskeletal systems such as the beaded filament (BF) and spectrin-actin networks contribute to mammalian lens biomechanics; mutations or deletion in these proteins alters lens biomechanics. Aquaporin 0 (AQP0), which constitutes ∼45% of the total membrane proteins of lens fiber cells, has been shown to function as a water channel and a structural cell-to-cell adhesion (CTCA) protein. Our recent ex vivo study on AQP0 knockout (AQP0 KO) mouse lenses showed the CTCA function of AQP0 could be crucial for establishing the refractive index gradient. However, biomechanical studies on the role of AQP0 are lacking. The present investigation used wild type (WT), AQP5 KO (AQP5{sup −/−}), AQP0 KO (heterozygous KO: AQP0{sup +/−}; homozygous KO: AQP0{sup −/−}; all in C57BL/6J) and WT-FVB/N mouse lenses to learn more about the role of fiber cell AQPs in lens biomechanics. Electron microscopic images exhibited decreases in lens fiber cell compaction and increases in extracellular space due to deletion of even one allele of AQP0. Biomechanical assay revealed that loss of one or both alleles of AQP0 caused a significant reduction in the compressive load-bearing capacity of the lenses compared to WT lenses. Conversely, loss of AQP5 did not alter the lens load-bearing ability. Compressive load-bearing at the suture area of AQP0{sup +/−} lenses showed easy separation while WT lens suture remained intact. These data from KO mouse lenses in conjunction with previous studies on lens-specific BF proteins (CP49 and filensin) suggest that AQP0 and BF proteins could act co-operatively in establishing normal lens biomechanics. We hypothesize that AQP0, with its prolific expression at the fiber cell membrane, could provide anchorage for cytoskeletal structures like BFs and

  11. Tonoplast Aquaporins Facilitate Lateral Root Emergence.

    Science.gov (United States)

    Reinhardt, Hagen; Hachez, Charles; Bienert, Manuela Désirée; Beebo, Azeez; Swarup, Kamal; Voß, Ute; Bouhidel, Karim; Frigerio, Lorenzo; Schjoerring, Jan K; Bennett, Malcolm J; Chaumont, Francois

    2016-03-01

    Aquaporins (AQPs) are water channels allowing fast and passive diffusion of water across cell membranes. It was hypothesized that AQPs contribute to cell elongation processes by allowing water influx across the plasma membrane and the tonoplast to maintain adequate turgor pressure. Here, we report that, in Arabidopsis (Arabidopsis thaliana), the highly abundant tonoplast AQP isoforms AtTIP1;1, AtTIP1;2, and AtTIP2;1 facilitate the emergence of new lateral root primordia (LRPs). The number of lateral roots was strongly reduced in the triple tip mutant, whereas the single, double, and triple tip mutants showed no or minor reduction in growth of the main root. This phenotype was due to the retardation of LRP emergence. Live cell imaging revealed that tight spatiotemporal control of TIP abundance in the tonoplast of the different LRP cells is pivotal to mediating this developmental process. While lateral root emergence is correlated to a reduction of AtTIP1;1 and AtTIP1;2 protein levels in LRPs, expression of AtTIP2;1 is specifically needed in a restricted cell population at the base, then later at the flanks, of developing LRPs. Interestingly, the LRP emergence phenotype of the triple tip mutants could be fully rescued by expressing AtTIP2;1 under its native promoter. We conclude that TIP isoforms allow the spatial and temporal fine-tuning of cellular water transport, which is critically required during the highly regulated process of LRP morphogenesis and emergence. PMID:26802038

  12. Are Aquaporins the Missing Transmembrane Osmosensors?

    Science.gov (United States)

    Hill, A E; Shachar-Hill, Y

    2015-08-01

    Regulation of cell volume is central to homeostasis. It is assumed to begin with the detection of a change in water potential across the bounding membrane, but it is not clear how this is accomplished. While examples of general osmoreceptors (which sense osmotic pressure in one phase) and stretch-activated ion channels (which require swelling of a cell or organelle) are known, effective volume regulation requires true transmembrane osmosensors (TMOs) which directly detect a water potential difference spanning a membrane. At present, no TMO molecule has been unambiguously identified, and clear evidence for mammalian TMOs is notably lacking. In this paper, we set out a theory of TMOs which requires a water channel spanning the membrane that excludes the major osmotic solutes, responds directly without the need for any other process such as swelling, and signals to other molecules associated with the magnitude of changing osmotic differences. The most likely molecules that are fit for this purpose and which are also ubiquitous in eukaryotic cells are aquaporins (AQPs). We review experimental evidence from several systems which indicates that AQPs are essential elements in regulation and may be functioning as TMOs; i.e. the first step in an osmosensing sequence that signals osmotic imbalance in a cell or organelle. We extend this concept to several systems of current interest in which the cellular involvement of AQPs as simple water channels is puzzling or counter-intuitive. We suggest that, apart from regulatory volume changes in cells, AQPs may also be acting as TMOs in red cells, secretory granules and microorganisms. PMID:25791748

  13. Pregnant phenotype in aquaporin 8-deficient mice

    Institute of Scientific and Technical Information of China (English)

    Xiao-yan SHA; Zheng-fang XIONG; Hui-shu LIU; Zheng ZHENG; Tong-hui MA

    2011-01-01

    Aim: Aquaporin 8 (AQP8) is expressed within the female reproductive system but its physiological function reminds to be elucidated.This study investigates the role of AQP8 during pregnancy using AQP8-knockout (AQP8-KO) mice.Methods: Homozygous AQP8-KO mice were mated, and the conception rate was recorded. AQP8-KO pregnant mice or their offspring were divided into 5 subgroups according to fetal gestational day (7, 13, 16, 18 GD) and newborn. Wild type C57 pregnant mice served as the control group. The number of pregnant mice, total embryos and atrophic embryos, as well as fetal weight, placental weight and placental area were recorded for each subgroup. The amount of amniotic fluid in each sac at 13, 16, and 18 GD was calculated. Statistical significance was determined by analysis of variance of factorial design and chi-square tests.Results: Conception rates did not differ significantly between AQP8-KO and wild type mice. AQP8-KO pregnant mice had a significantly higher number of embryos compared to wild type controls. Fetal/neonatal weight was also significantly greater in the AQP8-KO group compared to age-matched wild type controls. The amount of amniotic fluid was greater in AQP8-KO pregnant mice than wild type controis, although the FM/AFA (fetal weight/amniotic fluid amount) did not differ. While AQP8-KO placental weight was significantly larger than wild type controls, there was no evidence of placental pathology in either group.Conclusion: The results suggest that AQP8 deficiency plays an important role in pregnancy outcome.

  14. Pregnant phenotype in aquaporin 8-deficient mice

    Science.gov (United States)

    Sha, Xiao-yan; Xiong, Zheng-fang; Liu, Hui-shu; Zheng, Zheng; Ma, Tong-hui

    2011-01-01

    Aim: Aquaporin 8 (AQP8) is expressed within the female reproductive system but its physiological function reminds to be elucidated. This study investigates the role of AQP8 during pregnancy using AQP8-knockout (AQP8-KO) mice. Methods: Homozygous AQP8-KO mice were mated, and the conception rate was recorded. AQP8-KO pregnant mice or their offspring were divided into 5 subgroups according to fetal gestational day (7, 13, 16, 18 GD) and newborn. Wild type C57 pregnant mice served as the control group. The number of pregnant mice, total embryos and atrophic embryos, as well as fetal weight, placental weight and placental area were recorded for each subgroup. The amount of amniotic fluid in each sac at 13, 16, and 18 GD was calculated. Statistical significance was determined by analysis of variance of factorial design and chi-square tests. Results: Conception rates did not differ significantly between AQP8-KO and wild type mice. AQP8-KO pregnant mice had a significantly higher number of embryos compared to wild type controls. Fetal/neonatal weight was also significantly greater in the AQP8-KO group compared to age-matched wild type controls. The amount of amniotic fluid was greater in AQP8-KO pregnant mice than wild type controls, although the FM/AFA (fetal weight/amniotic fluid amount) did not differ. While AQP8-KO placental weight was significantly larger than wild type controls, there was no evidence of placental pathology in either group. Conclusion: The results suggest that AQP8 deficiency plays an important role in pregnancy outcome. PMID:21602842

  15. Recombinant production of human Aquaporin-1 to an exceptional high membrane density in Saccharomyces cerevisiae.

    Directory of Open Access Journals (Sweden)

    Julie Bomholt

    Full Text Available In the present paper we explored the capacity of yeast Saccharomyces cerevisiae as host for heterologous expression of human Aquaporin-1. Aquaporin-1 cDNA was expressed from a galactose inducible promoter situated on a plasmid with an adjustable copy number. Human Aquaporin-1 was C-terminally tagged with yeast enhanced GFP for quantification of functional expression, determination of sub-cellular localization, estimation of in vivo folding efficiency and establishment of a purification protocol. Aquaporin-1 was found to constitute 8.5 percent of total membrane protein content after expression at 15°C in a yeast host over-producing the Gal4p transcriptional activator and growth in amino acid supplemented minimal medium. In-gel fluorescence combined with western blotting showed that low accumulation of correctly folded recombinant Aquaporin-1 at 30°C was due to in vivo mal-folding. Reduction of the expression temperature to 15°C almost completely prevented Aquaporin-1 mal-folding. Bioimaging of live yeast cells revealed that recombinant Aquaporin-1 accumulated in the yeast plasma membrane. A detergent screen for solubilization revealed that CYMAL-5 was superior in solubilizing recombinant Aquaporin-1 and generated a monodisperse protein preparation. A single Ni-affinity chromatography step was used to obtain almost pure Aquaporin-1. Recombinant Aquaporin-1 produced in S. cerevisiae was not N-glycosylated in contrast to the protein found in human erythrocytes.

  16. Aquaporin-Based Biomimetic Polymeric Membranes: Approaches and Challenges

    DEFF Research Database (Denmark)

    Habel, Joachim Erich Otto; Hansen, Michael; Kynde, Søren;

    2015-01-01

    In recent years, aquaporin biomimetic membranes (ABMs) for water separation have gained considerable interest. Although the first ABMs are commercially available, there are still many challenges associated with further ABM development. Here, we discuss the interplay of the main components of ABMs...

  17. MAL decreases the internalization of the aquaporin-2 water channel.

    NARCIS (Netherlands)

    Kamsteeg, E.J.; Duffield, A.S.; Konings, I.B.M.; Spencer, J.; Pagel, P.; Deen, P.M.T.; Caplan, M.J.

    2007-01-01

    Body water homeostasis depends critically on the hormonally regulated trafficking of aquaporin-2 (AQP2) water channels in renal collecting duct epithelial cells. Several types of posttranslational modifications are clearly involved in controlling the distribution of AQP2 between intracellular vesicl

  18. Crystal Structure of an Ammonia-Permeable Aquaporin.

    Science.gov (United States)

    Kirscht, Andreas; Kaptan, Shreyas S; Bienert, Gerd Patrick; Chaumont, François; Nissen, Poul; de Groot, Bert L; Kjellbom, Per; Gourdon, Pontus; Johanson, Urban

    2016-03-01

    Aquaporins of the TIP subfamily (Tonoplast Intrinsic Proteins) have been suggested to facilitate permeation of water and ammonia across the vacuolar membrane of plants, allowing the vacuole to efficiently sequester ammonium ions and counteract cytosolic fluctuations of ammonia. Here, we report the structure determined at 1.18 Å resolution from twinned crystals of Arabidopsis thaliana aquaporin AtTIP2;1 and confirm water and ammonia permeability of the purified protein reconstituted in proteoliposomes as further substantiated by molecular dynamics simulations. The structure of AtTIP2;1 reveals an extended selectivity filter with the conserved arginine of the filter adopting a unique unpredicted position. The relatively wide pore and the polar nature of the selectivity filter clarify the ammonia permeability. By mutational studies, we show that the identified determinants in the extended selectivity filter region are sufficient to convert a strictly water-specific human aquaporin into an AtTIP2;1-like ammonia channel. A flexible histidine and a novel water-filled side pore are speculated to deprotonate ammonium ions, thereby possibly increasing permeation of ammonia. The molecular understanding of how aquaporins facilitate ammonia flux across membranes could potentially be used to modulate ammonia losses over the plasma membrane to the atmosphere, e.g., during photorespiration, and thereby to modify the nitrogen use efficiency of plants. PMID:27028365

  19. Aquaporin Inhibition by Gold(III) Compounds : New Insights

    NARCIS (Netherlands)

    Martins, Ana Paula; Ciancetta, Antonella; Batista de Almeida, Andreia; Marrone, Alessandro; Re, Nazzareno; Soveral, Graca; Casini, Angela

    2013-01-01

    Aquaporins (AQPs) are membrane water/glycerol channels with essential roles in biological systems, as well as being promising targets for therapy and imaging. Using a stopped-flow method, a series of gold(III), platinum(II) and copper(II) complexes bearing nitrogen donor ligands, such as 1,10-phenat

  20. Optimizing water permeability through the hourglass shape of aquaporins.

    Science.gov (United States)

    Gravelle, Simon; Joly, Laurent; Detcheverry, François; Ybert, Christophe; Cottin-Bizonne, Cécile; Bocquet, Lydéric

    2013-10-01

    The ubiquitous aquaporin channels are able to conduct water across cell membranes, combining the seemingly antagonist functions of a very high selectivity with a remarkable permeability. Whereas molecular details are obvious keys to perform these tasks, the overall efficiency of transport in such nanopores is also strongly limited by viscous dissipation arising at the connection between the nanoconstriction and the nearby bulk reservoirs. In this contribution, we focus on these so-called entrance effects and specifically examine whether the characteristic hourglass shape of aquaporins may arise from a geometrical optimum for such hydrodynamic dissipation. Using a combination of finite-element calculations and analytical modeling, we show that conical entrances with suitable opening angle can indeed provide a large increase of the overall channel permeability. Moreover, the optimal opening angles that maximize the permeability are found to compare well with the angles measured in a large variety of aquaporins. This suggests that the hourglass shape of aquaporins could be the result of a natural selection process toward optimal hydrodynamic transport. Finally, in a biomimetic perspective, these results provide guidelines to design artificial nanopores with optimal performances. PMID:24067650

  1. Water permeability of the mammalian cochlea: functional features of an aquaporin-facilitated water shunt at the perilymph-endolymph barrier.

    Science.gov (United States)

    Eckhard, A; Müller, M; Salt, A; Smolders, J; Rask-Andersen, H; Löwenheim, H

    2014-10-01

    The cochlear duct epithelium (CDE) constitutes a tight barrier that effectively separates the inner ear fluids, endolymph and perilymph, thereby maintaining distinct ionic and osmotic gradients that are essential for auditory function. However, in vivo experiments have demonstrated that the CDE allows for rapid water exchange between fluid compartments. The molecular mechanism governing water permeation across the CDE remains elusive. We computationally determined the diffusional (PD) and osmotic (Pf) water permeability coefficients for the mammalian CDE based on in silico simulations of cochlear water dynamics integrating previously derived in vivo experimental data on fluid flow with expression sites of molecular water channels (aquaporins, AQPs). The PD of the entire CDE (PD = 8.18 × 10(-5) cm s(-1)) and its individual partitions including Reissner's membrane (PD = 12.06 × 10(-5) cm s(-1)) and the organ of Corti (PD = 10.2 × 10(-5) cm s(-1)) were similar to other epithelia with AQP-facilitated water permeation. The Pf of the CDE (Pf = 6.15 × 10(-4) cm s(-1)) was also in the range of other epithelia while an exceptionally high Pf was determined for an epithelial subdomain of outer sulcus cells in the cochlear apex co-expressing AQP4 and AQP5 (OSCs; Pf = 156.90 × 10(-3) cm s(-1)). The Pf/PD ratios of the CDE (Pf/PD = 7.52) and OSCs (Pf/PD = 242.02) indicate an aqueous pore-facilitated water exchange and reveal a high-transfer region or "water shunt" in the cochlear apex. This "water shunt" explains experimentally determined phenomena of endolymphatic longitudinal flow towards the cochlear apex. The water permeability coefficients of the CDE emphasise the physiological and pathophysiological relevance of water dynamics in the cochlea in particular for endolymphatic hydrops and Ménière's disease. PMID:24385019

  2. Identification and Expression Analysis of Aquaporins in the Potato Psyllid, Bactericera cockerelli

    OpenAIRE

    Ibanez, Freddy; Hancock, Joseph; Tamborindeguy, Cecilia

    2014-01-01

    Aquaporin (AQPs) proteins transport water and uncharged low molecular-weight solutes across biological membranes. Six to 8 AQP genes have been identified in many insect species, but presently only three aquaporins have been characterized in phloem feeding insects. The objective of this study was to identify candidate AQPs in the potato psyllid, Bactericera cockerelli. Herein, we identified four candidate aquaporin cDNAs in B. cockerelli transcriptome. Phylogenetic analysis showed that candida...

  3. Identification of New Aquaporin Genes and Single Nucleotide Polymorphism in Bread Wheat

    OpenAIRE

    Pandey, B.; P.Sharma; Pandey, D.M.; I Sharma; Chatrath, R.

    2013-01-01

    Major facilitators of water movement through plant cell membranes include aquaporin proteins. Wheat is among the largest and most important cereal crops worldwide; however, unlike other model plants such as rice, maize and Arabidopsis, little has been reported on wheat major intrinsic proteins (MIPs). This study presents a comprehensive computational identification of 349 new wheat expressed sequence tags (ESTs), encoding 13 wheat aquaporin genes. Identified aquaporins consist of 6 plasma mem...

  4. Hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in a rat model of acute hyperammonemia

    DEFF Research Database (Denmark)

    Bjerring, Peter Nissen; Eefsen, Martin; Larsen, Fin Stolze;

    2011-01-01

    whether hypermagnesemia had an influence on brain content of glutamate, glutamine, and aquaporin-4 expression. The study consisted of three experiments: The first was a dose-finding study of four different dosing regimens of magnesium sulfate (MgSO4) in healthy rats. The second involved four groups of PCA......Intravenous infusion of magnesium sulfate prevents seizures in patients with eclampsia and brain edema after traumatic brain injury. Neuroprotection is achieved by controlling cerebral blood flow (CBF), intracranial pressure, neuronal glutamate release, and aquaporin-4 (Aqp4) expression. These...... rats receiving ammonia infusion/vehicle and MgSO4) /saline. The effect of MgSO(4) on mean arterial pressure (MAP), intracranial pressure (ICP), CBF, cerebral glutamate and glutamine, and aquaporin-4 expression was studied. Finally, the effect of MgSO4 on MAP, ICP, and CBF was studied, using two...

  5. Aquaporins 6-12 in the human eye

    DEFF Research Database (Denmark)

    Tran, Thuy Linh; Bek, Toke; Holm, Lars;

    2013-01-01

    Purpose: Aquaporins (AQPs) are widely expressed and have diverse distribution patterns in the eye. AQPs 0-5 have been localized at the cellular level in human eyes. We investigated the presence of the more recently discovered AQPs 6-12 in the human eye. Methods: RT-PCR was performed on fresh tissue...... from two human eyes divided into the cornea, corneal limbus, ciliary body and iris, lens, choroid, optic nerve, retina and sclera. Each structure was examined to detect the mRNA of AQPs 6-12. Twenty-one human eyes were examined using immunohistochemical and immunofluorescence techniques to determine...... structures of the human eye. The detection of these aquaporins in the eye implies a role that may be related not only to water transport but also to the transport of glycerol, lactate and ammonia, with importance for metabolism, especially in the retina....

  6. Aquaporin-Based Biomimetic Polymeric Membranes: Approaches and Challenges

    Directory of Open Access Journals (Sweden)

    Joachim Habel

    2015-07-01

    Full Text Available In recent years, aquaporin biomimetic membranes (ABMs for water separation have gained considerable interest. Although the first ABMs are commercially available, there are still many challenges associated with further ABM development. Here, we discuss the interplay of the main components of ABMs: aquaporin proteins (AQPs, block copolymers for AQP reconstitution, and polymer-based supporting structures. First, we briefly cover challenges and review recent developments in understanding the interplay between AQP and block copolymers. Second, we review some experimental characterization methods for investigating AQP incorporation including freeze-fracture transmission electron microscopy, fluorescence correlation spectroscopy, stopped-flow light scattering, and small-angle X-ray scattering. Third, we focus on recent efforts in embedding reconstituted AQPs in membrane designs that are based on conventional thin film interfacial polymerization techniques. Finally, we describe some new developments in interfacial polymerization using polyhedral oligomeric silsesquioxane cages for increasing the physical and chemical durability of thin film composite membranes.

  7. Distribution of aquaporins in the nasal passage of Octodon degus, a South-American desert rodent and its implications for water conservation Distribución de acuaporinas en los pasajes nasales de Octodon degus, un roedor de ambientes desérticos sudamericanos: implicaciones en la conservación de agua

    Directory of Open Access Journals (Sweden)

    PEDRO GALLARDO

    2008-03-01

    Full Text Available Rodents from arid and semiarid environments live under conditions where the spatial and temporal availability of water is limited. Octodon degus is a South-American desert-dwelling rodent inhabiting arid and semiarid habitats of central and northern Chile. Its survival depends on morphological, physiological and behavioral adaptations that allow water conservation. This rodent has a high urine concentrating ability, high capacity of fecal dehydration and low evaporative water loss, related to the ability of the nasal passages to condense water from the exhaled air; this water must be absorbed in order to avoid its accumulation in the nasal passages and potential loss through the nostrils. We hypothesize that aquaporins (AQPs might be present in the nasal mucosa; therefore, we studied the distribution of AQP-1, AQP-2, AQP-3 and AQP-4 through immunocytochemistry. Intense AQP-1 labeling was observed throughout the subepithelial vascular network; no AQP-1 immunoreactivity was detected in olfactory and non-olfactory epithelial cells. No signal was detected for AQP-2 and 4. AQP-3 distribution was restricted to the surface non-olfactory epithelial cells lining the turbinates in narrow passages and blind spaces. Therefore, AQP-1 and AQP-3 coincided at the level of the turbinates, although in different cell types which suggest a pathway for water removal from the nasal surface first through AQP-3 in non-olfactory epithelial cells and then into the capillary lumen through AQP-1Los roedores de ambientes áridos y semiáridos viven bajo una disponibilidad limitada de agua tanto espacial como temporal. Octodon degus es un roedor sudamericano que habita ambientes áridos y semiáridos del norte y zona central de Chile. Su supervivencia depende de adaptaciones morfológicas, fisiológicas y conductuales que permiten optimizar la conservación de agua. Este tiene una alta capacidad de concentración urinaria y de deshidratación de la fecas además de una baja

  8. Aquaporin 1 – a novel player in spinal cord injury

    OpenAIRE

    Nesic, O.; Lee, J.; Unabia, G. C.; Johnson, K.; Z. Ye; Vergara, L.; Hulsebosch, C. E.; Perez-Polo, J. R.

    2008-01-01

    The role of water channel aquaporin 1 (AQP-1) in uninjured or injured spinal cords is unknown. AQP-1 is weakly expressed in neurons and gray matter astrocytes, and more so in white matter astrocytes in uninjured spinal cords, a novel finding. As reported before, AQP-1 is also present in ependymal cells, but most abundantly in small diameter sensory fibers of the dorsal horn. Rat contusion spinal cord injury (SCI) induced persistent and significant four- to eightfold increases in AQP-1 levels ...

  9. The expanded spectrum of neuromyelitis optica: evidences for a new definition

    Directory of Open Access Journals (Sweden)

    Marco A Lana-Peixoto

    2012-10-01

    Full Text Available Neuromyelitis optica (NMO has been traditionally described as the association of recurrent or bilateral optic neuritis and longitudinally extensive transverse myelitis (LETM. Identification of aquaporin-4 antibody (AQP4-IgG has deeply changed the concept of NMO. A spectrum of NMO disorders (NMOSD has been formulated comprising conditions which include both AQP4-IgG seropositivity and one of the index events of the disease (recurrent or bilateral optic neuritis and LETM. Most NMO patients harbor asymptomatic brain MRI lesions, some of them considered as typical of NMO. Some patients with aquaporin-4 autoimmunity present brainstem, hypothalamic or encephalopathy symptoms either preceding an index event or occurring isolatedly with no evidence of optic nerve or spinal involvement. On the opposite way, other patients have optic neuritis or LETM in association with typical lesions of NMO on brain MRI and yet are AQP4-IgG seronegative. An expanded spectrum of NMO disorders is proposed to include these cases.

  10. Sub-genomic level sequence analysis of the aquaporin multi-gene family in cotton

    Science.gov (United States)

    Aquaporins function mainly as water transport channel proteins that facilitate water movement across intracellular and intercellular membranes in most living organisms. Plant aquaporins belong to a multi-gene family and are commonly categorized into 5 subfamilies according to sequence similarity. Re...

  11. A Gold Coordination Compound as a Chemical Probe to Unravel Aquaporin-7 Function

    NARCIS (Netherlands)

    Madeira, Ana; de Almeida, Andreia; de Graaf, Chris; Camps, Marta; Zorzano, Antonio; Moura, Teresa F; Casini, Angela; Soveral, Graça

    2014-01-01

    Aquaporins (AQPs) are membrane water/glycerol channels that are involved in many physiological functions. Aquaporin-based modulators are predicted to have potential utility in the treatment of several diseases, as well as chemical tools to assess AQPs function in biological systems. We recently repo

  12. Regulation of Aquaporin Z osmotic permeability in ABA tri-block copolymer

    Directory of Open Access Journals (Sweden)

    Wenyuan Xie

    2015-08-01

    Full Text Available Aquaporins are transmembrane water channel proteins present in biological plasma membranes that aid in biological water filtration processes by transporting water molecules through at high speeds, while selectively blocking out other kinds of solutes. Aquaporin Z incorporated biomimetic membranes are envisaged to overcome the problem of high pressure needed, and holds great potential for use in water purification processes, giving high flux while keeping energy consumption low. The functionality of aquaporin Z in terms of osmotic permeability might be regulated by factors such as pH, temperature, crosslinking and hydrophobic thickness of the reconstituted bilayers. Hence, we reconstituted aquaporin Z into vesicles that are made from a series of amphiphilic block copolymers PMOXA-PDMS-PMOXAs with various hydrophobic molecular weights. The osmotic permeability of aquaporin Z in these vesicles was determined through a stopped-flow spectroscopy. In addition, the temperature and pH value of the vesicle solutions were adjusted within wide ranges to investigate the regulation of osmotic permeability of aquaporin Z through external conditions. Our results show that aquaporin Z permeability was enhanced by hydrophobic mismatch. In addition, the water filtration mechanism of aquaporin Z is significantly affected by the concentration of H+ and OH- ions.

  13. Targeting Aquaporin Function : Potent Inhibition of Aquaglyceroporin-3 by a Gold-Based Compound

    NARCIS (Netherlands)

    Martins, Ana Paula; Marrone, Alessandro; Ciancetta, Antonella; Galan Cobo, Ana; Echevarria, Miriam; Moura, Teresa F.; Re, Nazzareno; Casini, Angela; Soveral, Graca

    2012-01-01

    Aquaporins (AQPs) are membrane channels that conduct water and small solutes such as glycerol and are involved in many physiological functions. Aquaporin-based modulator drugs are predicted to be of broad potential utility in the treatment of several diseases. Until today few AQP inhibitors have bee

  14. Molecular Pathogenesis of Neuromyelitis Optica

    Directory of Open Access Journals (Sweden)

    Simon A Broadley

    2012-10-01

    Full Text Available Neuromyelitis optica (NMO is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions in the optic nerves and spinal cord. An autoantibody (NMO IgG against aquaporin-4 (AQP4, a water channel expressed on astrocytes is thought to be causative. Peripheral production of the antibody is triggered by an unknown process in genetically susceptible individuals. Anti-AQP4 antibody enters the central nervous system (CNS when the blood brain barrier is made permeable and has high affinity for orthogonal array particles of AQP4. Like other autoimmune diseases, Th17 cells and their effector cytokines (such as interleukin 6 have been implicated in pathogenesis. AQP4 expressing peripheral organs are not affected by NMO IgG, but the antibody causes extensive astrocytic loss in specific regions of the CNS through complement mediated cytotoxicity. Demyelination occurs during the inflammatory process and is probably secondary to oligodendrocyte apoptosis subsequent to loss of trophic support from astrocytes. Ultimately, extensive axonal injury leads to severe disability. Despite rapid advances in the understanding of NMO pathogenesis, unanswered questions remain, particularly with regards to disease mechanisms in NMO IgG seronegative cases. Increasing knowledge of the molecular pathology is leading to improved treatment strategies.

  15. 横贯性脊髓炎患者水通道蛋白-4抗体的检测与临床特征分析%Detection and the significance of aquaporin-4 antibody in patients with transverse myelitis

    Institute of Scientific and Technical Information of China (English)

    解龙昌; 单福兰; 郑杨波; 陈梦宇; 杨洁; 高聪; 杨宁; 龙友明; 杨新光

    2014-01-01

    目的检测不同类型的横贯性脊髓炎(TM)患者水通道蛋白-4(AQP4)抗体,分析AQP4抗体的临床意义。方法研究对象为能获取标本检测AQP4抗体的TM患者。 AQP4抗体通过间接免疫荧光的细胞法检测。结果共纳入TM 患者92例,68例(73.9%)诊断为长节段横贯性脊髓炎( LETM ),其余24例诊断为非LETM。 LETM患者中39例(57.4%,39/68)AQP4抗体阳性,非LETM患者中2例(8.3%,2/24)AQP4抗体阳性。患者分成AQP4抗体阳性组与AQP4抗体阴性组,阳性组女性比例、LETM比例、脊髓炎复发率和功能残障评分均高于阴性组(P<0.05)。在亚群分析中,将68例LETM患者分成AQP4抗体阳性与AQP4阴性两组,可见阳性LETM组女性比例和脊髓炎复发率高于阴性LETM组( P<0.05)。 Spearman 相关性分析显示:AQP4抗体与女性(r=0.471,P<0.0001)、LETM(r=0.433,P<0.0001)及复发(r=0.560,P<0.0001)相关。结论 AQP4抗体主要出现于LETM女性患者,抗体阳性患者比阴性患者更容易复发。%Objective To evaluate the significance of AQP 4 antibody in patients with different types of transverse myelitis (TM).Methods Patients with TM were included retrospectively between 2003 and 2014.AQP4 antibodies were detected by an indirect immunofluorescence assay employing HEK -293 cells transected with recombinant human AQP4.Results A total of 92 patients were included , among whom 68 patients with longitudinal extensive transverse my-elitis (LETM) and 24 patients with non-LETM.Positive AQP4 was observed in 39 LETM (57.4%, 39/68) and 2 n-LETM (8.3%, 2/24) patients.The female ratio, LETM ratio, relapsing case and EDSS were significantly higher in AQP4 positive patients than those in negative ones .In the patients with LETM , significantly more female and relapsing ca-ses were observed in AQP4 positive subjects than negatives .Correlation analysis showed that female , LETM and

  16. Effects of propofol on ammonium chloride-exposed astrocyte morphology and aquaporin-4 expression

    Institute of Scientific and Technical Information of China (English)

    Hanjian Chen; Caifei Pan; Peng Guo; Yueying Zheng; Shengmei Zhu

    2011-01-01

    Ammonia induces astrocyte swelling, which is strongly associated with overexpression of aquaporin-4.However, the mechanisms by which ammonia induces astrocyte swelling, and subsequently upregulating aquaporin-4 expression, remain unknown.In the present study,astrocytes were cultured in vitro and exposed to ammonium chloride (NH4CI), followed by propofol,protein kinase C agonist, or antagonist, respectively.Astrocyte morphology was observed by light microscopy, and aquaporin-4 expression was detected by western blot analysis.Results showed that propofol or protein kinase C agonist significantly attenuated the degree of NH4CI-induced astrocyte swelling and inhibited increased aquaporin-4 expression.Propofol treatment inhibited aquaporin-4 overexpression in cultured astrocyte induced by NH4CI; protein kinase C pathway activation is potentially involved.

  17. Free energy calculation of permeation through aquaporin-5

    Science.gov (United States)

    Bastien, David

    The work of this paper continues upon the large area of research being done on aquaporins (AQPs). AQPs are proteins that take on the role of facilitating the transfer of substances, mainly water, across cell membranes. There are many different types of AQPs, with each of these highly selective proteins conducting only certain solutes, along with unique permeability rates. The permeation characteristics of aquaporins rely mostly on the residue hydrophobicity and steric restraints of the aromatic arginine (ar/R) region of the protein channel. The purpose of this paper is to analyze the structures of aquaporin-5 (AQP5) and aquaglycerolporin (Glpf), including a radius profile of the respective protein channels, and to compare them to permeation events using steered molecular dynamics (SMD) pulling simulations. Two in silico experiments are performed in order to achieve the free Energy landscape of a single water molecule permeating through the four channels of both Aqp5 and GlpF. The equilibrium free energy curves are calculated from the non-equilibrium, irreversible work measurements using the fluctuation-dissipation theorem (FDT) of Brownian dynamicis (BD). The free energy profiles are then compared and related to the structural profiles of AQP5 and GlpF. The change in free energy across the ar/R region in AQP5 is found to be reasonably larger than that of GlpF. The free energy profiles of AQP5 and GlpF agree with the diameter profile of the channels respectively. Furthermore, free energy calculations are computed for the permeation of Na+ and Cl- ions through the central pore of Aqp5, which provide some insight into the structural mechanisms of AQP5. The free energy barrier for ion transport through the central pore is found to be very large, peaking at around 11 Kcal/mol for chloride and 20 Kcal/mol for sodium.

  18. Seronegative Neuromyelitis Optica Spectrum - The challenges on disease definition and pathogenesis

    Directory of Open Access Journals (Sweden)

    Douglas Kazutoshi Sato

    2014-06-01

    Full Text Available Neuromyelitis optica spectrum disorders (NMOSD are characterized by severe optic neuritis and/or longitudinally extensive transverse myelitis, and some brain lesions are also unique to NMOSD. Serum autoantibodies against aquaporin-4 (AQP4 are detected in most cases of NMOSD. However, some patients with NMOSD remain seronegative despite repetitive testing during attacks with highly sensitive cell-based assays. The differential diagnosis of NMOSD is not restricted to multiple sclerosis and it includes many diseases that can produce longitudinally extensive myelitis and/or optic neuritis. We review the clinical features, imaging, and laboratory findings that can be helpful on the diagnostic work-up, discuss the differences between AQP4 antibody positive and negative patients with NMOSD, including features of NMOSD with antibodies against myelin oligodendrocyte glycoprotein.

  19. Genome-wide analysis and expression profiling of the Solanum tuberosum aquaporins.

    Science.gov (United States)

    Venkatesh, Jelli; Yu, Jae-Woong; Park, Se Won

    2013-12-01

    Aquaporins belongs to the major intrinsic proteins involved in the transcellular membrane transport of water and other small solutes. A comprehensive genome-wide search for the homologues of Solanum tuberosum major intrinsic protein (MIP) revealed 41 full-length potato aquaporin genes. All potato aquaporins are grouped into five subfamilies; plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), NOD26-like intrinsic proteins (NIPs), small basic intrinsic proteins (SIPs) and x-intrinsic proteins (XIPs). Functional predictions based on the aromatic/arginine (ar/R) selectivity filters and Froger's positions showed a remarkable difference in substrate transport specificity among subfamilies. The expression pattern of potato aquaporins, examined by qPCR analysis, showed distinct expression profiles in various organs and tuber developmental stages. Furthermore, qPCR analysis of potato plantlets, subjected to various abiotic stresses revealed the marked effect of stresses on expression levels of aquaporins. Taken together, the expression profiles of aquaporins imply that aquaporins play important roles in plant growth and development, in addition to maintaining water homeostasis in response to environmental stresses. PMID:24215931

  20. Can Stabilization and Inhibition of Aquaporins Contribute to Future Development of Biomimetic Membranes?

    Science.gov (United States)

    To, Janet; Torres, Jaume

    2015-01-01

    In recent years, the use of biomimetic membranes that incorporate membrane proteins, i.e., biomimetic-hybrid membranes, has increased almost exponentially. Key membrane proteins in these systems have been aquaporins, which selectively permeabilize cellular membranes to water. Aquaporins may be incorporated into synthetic lipid bilayers or to more stable structures made of block copolymers or solid-state nanopores. However, translocation of aquaporins to these alien environments has adverse consequences in terms of performance and stability. Aquaporins incorporated in biomimetic membranes for use in water purification and desalination should also withstand the harsh environment that may prevail in these conditions, such as high pressure, and presence of salt or other chemicals. In this respect, modified aquaporins that can be adapted to these new environments should be developed. Another challenge is that biomimetic membranes that incorporate high densities of aquaporin should be defect-free, and this can only be efficiently ascertained with the availability of completely inactive mutants that behave otherwise like the wild type aquaporin, or with effective non-toxic water channel inhibitors that are so far inexistent. In this review, we describe approaches that can potentially be used to overcome these challenges. PMID:26266425

  1. Can Stabilization and Inhibition of Aquaporins Contribute to Future Development of Biomimetic Membranes?

    Directory of Open Access Journals (Sweden)

    Janet To

    2015-08-01

    Full Text Available In recent years, the use of biomimetic membranes that incorporate membrane proteins, i.e., biomimetic-hybrid membranes, has increased almost exponentially. Key membrane proteins in these systems have been aquaporins, which selectively permeabilize cellular membranes to water. Aquaporins may be incorporated into synthetic lipid bilayers or to more stable structures made of block copolymers or solid-state nanopores. However, translocation of aquaporins to these alien environments has adverse consequences in terms of performance and stability. Aquaporins incorporated in biomimetic membranes for use in water purification and desalination should also withstand the harsh environment that may prevail in these conditions, such as high pressure, and presence of salt or other chemicals. In this respect, modified aquaporins that can be adapted to these new environments should be developed. Another challenge is that biomimetic membranes that incorporate high densities of aquaporin should be defect-free, and this can only be efficiently ascertained with the availability of completely inactive mutants that behave otherwise like the wild type aquaporin, or with effective non-toxic water channel inhibitors that are so far inexistent. In this review, we describe approaches that can potentially be used to overcome these challenges.

  2. Comparative analysis of sequences, polymorphisms and topology of yeasts aquaporins and aquaglyceroporins.

    Science.gov (United States)

    Sabir, Farzana; Loureiro-Dias, Maria C; Prista, Catarina

    2016-05-01

    Efficient homeostasis of water and glycerol is a prerequisite for osmoregulation and other aspects of yeasts life. The cellular status of these molecules is often associated with functional presence of aquaporins and aquaglyceroporins. The present study provides a detailed updated analysis of aquaporins and aquaglyceroporins in 47 yeast species. A comprehensive analysis of aquaporins and aquaglyceroporins in 38 strains of Saccharomyces cerevisiae from different ecological niches is also presented. The functionality of specific aquaporins in yeasts has been associated with their adaptation requirements in different environmental conditions. In the present study, various inactivating mutations in aquaporin sequences were found in strains of S. cerevisiae Likewise, several new interesting polymorphisms in aquaglyceroporin sequences of some commercial wine and brewing strains, vineyard and bakery strains were also observed. Conceivably, both in the case of aquaporins and aquaglyceroporins inactivating mutations resulted in competitive advantage in selected environments. Topology and conservation of important regulatory residues within all sequences are also analyzed. We expect that the present review may contribute to establish the functional relevance of aquaporins/aquaglyceroporins for various aspects of yeasts physiology. PMID:27001976

  3. Preparative scale production of functional mouse aquaporin 4 using different cell-free expression modes.

    Directory of Open Access Journals (Sweden)

    Lei Kai

    Full Text Available The continuous progress in the structural and functional characterization of aquaporins increasingly attracts attention to study their roles in certain mammalian diseases. Although several structures of aquaporins have already been solved by crystallization, the challenge of producing sufficient amounts of functional proteins still remains. CF (cell free expression has emerged in recent times as a promising alternative option in order to synthesize large quantities of membrane proteins, and the focus of this report was to evaluate the potential of this technique for the production of eukaryotic aquaporins. We have selected the mouse aquaporin 4 as a representative of mammalian aquaporins. The protein was synthesized in an E. coli extract based cell-free system with two different expression modes, and the efficiencies of two modes were compared. In both, the P-CF (cell-free membrane protein expression as precipitate mode generating initial aquaporin precipitates as well as in the D-CF (cell-free membrane protein expression in presence of detergent mode, generating directly detergent solubilized samples, we were able to obtain mg amounts of protein per ml of cell-free reaction. Purified aquaporin samples solubilized in different detergents were reconstituted into liposomes, and analyzed for the water channel activity. The calculated P(f value of proteoliposome samples isolated from the D-CF mode was 133 µm/s at 10°C, which was 5 times higher as that of the control. A reversible inhibitory effect of mercury chloride was observed, which is consistent with previous observations of in vitro reconstituted aquaporin 4. In this study, a fast and convenient protocol was established for functional expression of aquaporins, which could serve as basis for further applications such as water filtration.

  4. Rapid Identification of Novel Inhibitors of the Human Aquaporin-1 Water Channel.

    Science.gov (United States)

    Patil, Rajkumar V; Xu, Shouxi; van Hoek, Alfred N; Rusinko, Andrew; Feng, Zixia; May, Jesse; Hellberg, Mark; Sharif, Najam A; Wax, Martin B; Irigoyen, Macarena; Carr, Grant; Brittain, Tom; Brown, Peter; Colbert, Damon; Kumari, Sindhu; Varadaraj, Kulandaiappan; Mitra, Alok K

    2016-05-01

    Aquaporins (AQPs) are a family of membrane proteins that function as channels facilitating water transport in response to osmotic gradients. These play critical roles in several normal physiological and pathological states and are targets for drug discovery. Selective inhibition of the AQP1 water channel may provide a new approach for the treatment of several disorders including ocular hypertension/glaucoma, congestive heart failure, brain swelling associated with a stroke, corneal and macular edema, pulmonary edema, and otic disorders such as hearing loss and vertigo. We developed a high-throughput assay to screen a library of compounds as potential AQP1 modulators by monitoring the fluorescence dequenching of entrapped calcein in a confluent layer of AQP1-overexpressing CHO cells that were exposed to a hypotonic shock. Promising candidates were tested in a Xenopus oocyte-swelling assay, which confirmed the identification of two lead classes of compounds belonging to aromatic sulfonamides and dihydrobenzofurans with IC50 s in the low micromolar range. These selected compounds directly inhibited water transport in AQP1-enriched stripped erythrocyte ghosts and in proteoliposomes reconstituted with purified AQP1. Validation of these lead compounds, by the three independent assays, establishes a set of attractive AQP1 blockers for developing novel, small-molecule functional modulators of human AQP1. PMID:26685080

  5. Isolation of a fruit ripening-related tonoplast aquaporin (GjTIP) gene from Gardenia jasminoides

    OpenAIRE

    Gao, Lan; Guo, Yi-Jun

    2013-01-01

    Aquaporins are membrane water channels that play critical roles in controlling the water content of cells and tissues. In this work, a full-length cDNA encoding putative aquaporins was isolated from Gardenia jasminoides fruit cDNA library. The GjTIP cDNA is 1188 bp, contains a predicted 774 bp open reading frame that encodes 257 amino acids. A phylogenetic analysis conducted with previously characterized aquaporins from other plant species indicates that the cDNA encode putative tonoplast aqu...

  6. Number and regulation of protozoan aquaporins reflect environmental complexity.

    Science.gov (United States)

    Von Bülow, Julia; Beitz, Eric

    2015-08-01

    Protozoa are a diverse group of unicellular eukaryotes. Evidence has accumulated that protozoan aquaporin water and solute channels (AQP) contribute to adaptation in changing environments. Intracellular protozoan parasites live a well-sheltered life. Plasmodium spp. express a single AQP, Toxoplasma gondii two, while Trypanosoma cruzi and Leishamnia spp. encode up to five AQPs. Their AQPs are thought to import metabolic precursors and simultaneously to dispose of waste and to help parasites survive osmotic stress during transmission to and from the insect vector or during kidney passages. Trypanosoma brucei is a protozoan parasite that swims freely in the human blood. Expression and intracellular localization of the three T. brucei AQPs depend on the stage of differentiation during the life cycle, suggesting distinct roles in energy generation, metabolism, and cell motility. Free-living amoebae are in direct contact with the environment, encountering severe and sudden changes in the availability of nutrition, and in the osmotic conditions due to rainfall or drought. Amoeba proteus expresses a single AQP that is present in the contractile vacuole complex required for osmoregulation, whereas Dictyostelium discoideum expresses four AQPs, of which two are present in the single-celled amoeboidal stage and two more in the later multicellular stages preceding spore formation. The number and regulation of protozoan aquaporins may reflect environmental complexity. We highlight the gated AqpB from D. discoideum as an example of how life in the wild is challenged by a complex AQP structure-function relationship. PMID:26338868

  7. Aquaporin expression patterns in the developing mouse salivary gland.

    Science.gov (United States)

    Larsen, Helga S; Ruus, Ann-Kristin; Galtung, Hilde Kanli

    2009-12-01

    Little is known about the presence of the various membrane-located water channels, aquaporins (AQP), during the prenatal and postnatal development of the mouse submandibular salivary gland (SMG). To learn more about AQPs in the developing aspect of salivary glands, we investigated trends in the expression patterns of several AQPs using the embryonic, early postnatal, and young adult mouse SMGs as models. We have chosen AQPs previously found in salivary glands in other animals. Transcripts of AQPs 1, 3, 4, 5, and 8 were detected by reverse transcription-polymerase chain reaction (RT-PCR) and quantified. Aquaporin proteins 1, 3, 4, and 5, but not AQP protein 8, were detected and quantified using western blotting. The various AQPs showed distinct transcript and protein-expression patterns. The change in trends may indicate that the importance of the various AQPs varies throughout the developmental stages in the mouse SMG. Their presence might be related to cell adhesion, migration, proliferation, apoptosis, transepithelial transport, osmosensing, or cell volume regulation; all roles that in the literature are linked to the various AQPs. Overall, this study demonstrates that AQP presentation varies and has a specific expression pattern during the development of mouse SMG. This feature may be important for glandular anatomical and physiological development. PMID:20121927

  8. The three-dimensional structure of human erythrocyte aquaporin CHIP.

    Science.gov (United States)

    Walz, T; Smith, B L; Agre, P; Engel, A

    1994-07-01

    Water-permeable membranes of several plant and mammalian tissues contain specific water channel proteins, the 'aquaporins'. The best characterized aquaporin is CHIP, a 28 kDa red blood cell channel-forming integral protein. Isolated CHIP and Escherichia coli lipids may be assembled into 2-D crystals for structural analyses. Here we present (i) a structural characterization of the solubilized CHIP oligomers, (ii) projections of CHIP arrays after negative staining or metal-shadowing, and (iii) the 3-D structure at 1.6 nm resolution. Negatively stained CHIP oligomers exhibited a side length of 6.9 nm with four-fold symmetry, and a mass of 202 +/- 3 kDa determined by scanning transmission electron microscopy. Reconstituted into lipid bilayers, CHIP formed 2-D square lattices with unit cell dimensions a = b = 9.6 nm and a p422(1) symmetry. The 3-D map revealed that CHIP tetramers contain central stain-filled depressions about the fourfold axis. These cavities extend from both sides into the transbilayer domain of the molecule leaving only a thin barrier to be penetrated by the water pores. Although CHIP monomers behave as independent pores, we propose that their particular structure requires tetramerization for stable integration into the bilayer. PMID:7518771

  9. Neuromyelitis optica IgG in the cerebrospinal fluid induces astrocytopathy in optic nerve

    DEFF Research Database (Denmark)

    Soelberg, Kerstin; Lillevang, Søren Thue; Mørch, Marlene;

    Background: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Optic neuritis (ON) is believed to be immune-mediated and is associated with AQP4-IgG in NMOSD-ON. The...

  10. Plant plasma membrane aquaporins in natural vesicles as potential stabilizers and carriers of glucosinolates.

    Science.gov (United States)

    Martínez-Ballesta, Maria Del Carmen; Pérez-Sánchez, Horacio; Moreno, Diego A; Carvajal, Micaela

    2016-07-01

    Their biodegradable nature and ability to target cells make biological vesicles potential nanocarriers for bioactives delivery. In this work, the interaction between proteoliposomes enriched in aquaporins derived from broccoli plants and the glucosinolates was evaluated. The vesicles were stored at different temperatures and their integrity was studied. Determination of glucosinolates, showed that indolic glucosinolates were more sensitive to degradation in aqueous solution than aliphatic glucosinolates. Glucoraphanin was stabilized by leaf and root proteoliposomes at 25°C through their interaction with aquaporins. An extensive hydrogen bond network, including different aquaporin residues, and hydrophobic interactions, as a consequence of the interaction between the linear alkane chain of glucoraphanin and Glu31 and Leu34 protein residues, were established as the main stabilizing elements. Combined our results showed that plasma membrane vesicles from leaf and root tissues of broccoli plants may be considered as suitable carriers for glucosinolate which stabilization can be potentially attributed to aquaporins. PMID:27022872

  11. Integrative sequence and tissue expression profiling of chicken and mammalian aquaporins

    OpenAIRE

    Raphael D. Isokpehi; Rajnarayanan, Rajendram V.; Jeffries, Cynthia D.; Oyeleye, Tolulola O.; Cohly, Hari HP

    2009-01-01

    Background Proteins that selectively transport water across the membranes of cells are recognized as important in the normal functioning of the body systems of vertebrates. There are 13 known mammalian aquaporins (AQP0 to AQP12), some of which have been shown to have unexpected cellular roles beyond transmembrane water transport. The availability of non-mammalian vertebrate animal models has the potential to provide insight into the emergence of diverse function in the aquaporins. The domesti...

  12. Preparative Scale Production of Functional Mouse Aquaporin 4 Using Different Cell-Free Expression Modes

    OpenAIRE

    Kai, Lei; Kaldenhoff, Ralf; Lian, Jiazhang; Zhu, Xiangcheng; Dötsch, Volker; Bernhard, Frank; Cen, Peilin; Xu, Zhinan

    2010-01-01

    The continuous progress in the structural and functional characterization of aquaporins increasingly attracts attention to study their roles in certain mammalian diseases. Although several structures of aquaporins have already been solved by crystallization, the challenge of producing sufficient amounts of functional proteins still remains. CF (cell free) expression has emerged in recent times as a promising alternative option in order to synthesize large quantities of membrane proteins, and ...

  13. Identification of new aquaporin genes and single nucleotide polymorphism in bread wheat.

    Science.gov (United States)

    Pandey, B; Sharma, P; Pandey, D M; Sharma, I; Chatrath, R

    2013-01-01

    Major facilitators of water movement through plant cell membranes include aquaporin proteins. Wheat is among the largest and most important cereal crops worldwide; however, unlike other model plants such as rice, maize and Arabidopsis, little has been reported on wheat major intrinsic proteins (MIPs). This study presents a comprehensive computational identification of 349 new wheat expressed sequence tags (ESTs), encoding 13 wheat aquaporin genes. Identified aquaporins consist of 6 plasma membrane intrinsic proteins (PIP) and 1 TIP showing high sequence similarity with rice aquaporins. We also identified 4 NOD26-like intrinsic proteins (NIP) and 2 SIP members that showed more divergence. Further, expression analysis of the aquaporin genes using the available EST information in UniGene revealed their transcripts were differentially regulated in various stress- and tissue-specific libraries. Allele specific Polymerase chain reaction (PCR) primers based on single nucleotide polymorphism (SNP) were designed using PIP as the target gene and validated on a core set of Indian wheat genotypes. A 3D theoretical model of the wheat aquaporin protein was built by homology modeling and could prove to be useful in the further functional characterization of this protein. Collectively with expression and bioinformatics analysis, our results support the idea that the genes identified in this study signify an important genetic resource providing potential targets to modify the water use properties of wheat. PMID:24250219

  14. Comment on: Cloning and characterization of porcine aquaporin 1 water channel expressed extensively in the gastrointestinal system

    Institute of Scientific and Technical Information of China (English)

    Ali Mobasheri

    2006-01-01

    @@ TO THE EDITOR Sir, I read with great interest the recently published article in the World Journal of Gastroenterology by Jin and co-workers[1] on the cloning and characterization of porcine aquaporin 1 water channel from the pig liver and studies on its expression in the porcine gastrointestinal system. The authors should be congratulated for making this important and valuable contribution to the field of aquaporin biology and porcine gastrointestinal physiology.However, there are a number of unresolved issues and controversies concerning the expression of aquaporins (especially aquaporin 1) in the gastrointestinal system that are worthy of additional comment and discussion by Jin and co-workers.

  15. Electrostatic tuning of permeation and selectivity in aquaporin water channels

    DEFF Research Database (Denmark)

    Jensen, Mogens O Stibius; Tajkhorshid, E.; Schulten, K.

    2003-01-01

    stronger than water-protein interactions, except near a conserved, positively charged Arg residue. We find that variations of the protein electrostatic field through the channel, owing to preserved structural features, completely explain the bipolar orientation of water. This orientation persists despite......Water permeation and electrostatic interactions between water and channel are investigated in the Escherichia coli glycerol uptake facilitator GlpF, a member of the aquaporin water channel family, by molecular dynamics simulations. A tetrameric model of the channel embedded in a 16:0/ 18:1c9......-palmitoyloleylphosphatidylethanolamine membrane was used for the simulations. During the simulations, water molecules pass through the channel in single file. The movement of the single. le water molecules through the channel is concerted, and we show that it can be described by a continuous-time random-walk model. The integrity of the...

  16. Aquaporin-1 is a Maxwell's Demon in the Body

    CERN Document Server

    Shu, Liangsuo; Xiaokang,; Qian, Liu Xin; Huang, Suyi; Jin, Shiping; Yang, Baoxue

    2015-01-01

    Aquaporin-1 (AQP1) is a membrane protein which is selectively permeable to water. Due to its hourglass shape, AQP1 can sense the information of solute molecules in osmosis. At the cost of consuming this information, AQP1 can move water against its chemical potential gradient: it works as one kind of Maxwell's Demon. This effect was detected quantitatively by measuring the water osmosis of mice erythrocytes. This ability may protect the erythrocytes from the eryptosis elicited by osmotic shock when they move in the kidney, where a large gradient of urea is required for the urine concentrating mechanism. This finding anticipates a new beginning of inquiries into the complicated relationships among mass, energy and information in bio-systems.

  17. Expression of Aquaporin-6 in Rat Retinal Ganglion Cells.

    Science.gov (United States)

    Jang, Sun Young; Lee, Eung Suk; Ohn, Young-Hoon; Park, Tae Kwann

    2016-08-01

    Several aquaporins (AQPs) have been identified to be present in the eyes, and it has been suggested that they are involved in the movement of water and small solutes. AQP6, which has low water permeability and transports mainly anions, was recently discovered in the eyes. In the present study, we investigate the localization of AQP6 in the rat retina and show that AQP6 is selectively localized to the ganglion cell layer and the outer plexiform layer. Along with the gradual decrease in retinal ganglion cells after a crushing injury of optic nerve, immunofluorescence signals of AQP6 gradually decreased. Confocal microscope images confirmed AQP6 expression in retinal ganglion cells and Müller cells in vitro. Therefore, AQP6 might participate in water and anion transport in these cells. PMID:26526333

  18. Structural determinants of water permeation through aquaporin-1

    Science.gov (United States)

    Murata, Kazuyoshi; Mitsuoka, Kaoru; Hirai, Teruhisa; Walz, Thomas; Agre, Peter; Heymann, J. Bernard; Engel, Andreas; Fujiyoshi, Yoshinori

    2000-10-01

    Human red cell AQP1 is the first functionally defined member of the aquaporin family of membrane water channels. Here we describe an atomic model of AQP1 at 3.8Å resolution from electron crystallographic data. Multiple highly conserved amino-acid residues stabilize the novel fold of AQP1. The aqueous pathway is lined with conserved hydrophobic residues that permit rapid water transport, whereas the water selectivity is due to a constriction of the pore diameter to about 3Å over a span of one residue. The atomic model provides a possible molecular explanation to a longstanding puzzle in physiology-how membranes can be freely permeable to water but impermeable to protons.

  19. Preparation of supported lipid membranes for aquaporin Z incorporation.

    Science.gov (United States)

    Li, Xuesong; Wang, Rong; Tang, Chuyang; Vararattanavech, Ardcharaporn; Zhao, Yang; Torres, Jaume; Fane, Tony

    2012-06-01

    There has been a recent surge of interest to mimic the performance of natural cellular membranes by incorporating water channel proteins-aquaporins (AQPs) into various ultrathin films for water filtration applications. To make biomimetic membranes one of the most crucial steps is preparing a defect-free platform for AQPs incorporation on a suitable substrate. In this study two methods were used to prepare supported lipid membranes on NF membrane surfaces under a benign pH condition of 7.8. One method was direct vesicle fusion on a hydrophilic membrane NF-270; the other was vesicle fusion facilitated by hydraulic pressure on a modified hydrophilic NF-270 membrane whose surface has been spin-coated with positively charged lipids. Experiments revealed that the supported lipid membrane without AQPs prepared by the spin coating plus vesicle fusion had a much lower defect density than that prepared by vesicle fusion alone. It appears that the surface roughness and charge are the main factors determining the quality of the supported lipid membrane. Aquaporin Z (AqpZ) proteins were successfully incorporated into 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes and its permeability was measured by the stopped-flow experimental procedure. However, after the proteoliposomes have been fused onto the modified substrate, the AqpZ function in the resultant membrane was not observed and AFM images showed distinct aggregations of unfused proteoliposomes or AqpZ proteins on the substrate surface. It is speculated that the inhibition of AqpZ function may be caused by the low lipid mobility on the NF membrane surface. Further investigations to evaluate and optimize the structure-performance relationship are required. PMID:22386862

  20. Aquaporin family genes exhibit developmentally-regulated and host-dependent transcription patterns in the sea louse Caligus rogercresseyi.

    Science.gov (United States)

    Farlora, Rodolfo; Valenzuela-Muñoz, Valentina; Chávez-Mardones, Jacqueline; Gallardo-Escárate, Cristian

    2016-07-01

    Aquaporins are small integral membrane proteins that function as pore channels for the transport of water and other small solutes across the cell membrane. Considering the important roles of these proteins in several biological processes, including host-parasite interactions, there has been increased research on aquaporin proteins recently. The present study expands on the knowledge of aquaporin family genes in parasitic copepods, examining diversity and expression during the ontogeny of the sea louse Caligus rogercresseyi. Furthermore, aquaporin expression was evaluated during the early infestation of Atlantic (Salmo salar) and Coho salmon (Oncorhynchus kisutch). Deep transcriptome sequencing data revealed eight full length and two partial open reading frames belonging to the aquaporin protein family. Clustering analyses with identified Caligidae sequences revealed three major clades of aquaglyceroporins (Cr-Glp), classical aquaporin channels (Cr-Bib and Cr-PripL), and unorthodox aquaporins (Cr-Aqp12-like). In silico analysis revealed differential expression of aquaporin genes between developmental stages and between sexes. Male-biased expression of Cr-Glp1_v1 and female-biased expression of Cr-Bib were further confirmed in adults by RT-qPCR. Additionally, gene expressions were measured for seven aquaporins during the early infestation stage. The majority of aquaporin genes showed significant differential transcription expressions between sea lice parasitizing different hosts, with Atlantic salmon sea lice exhibiting overall reduced expression as compared to Coho salmon. The observed differences in the regulation of aquaporin genes may reveal osmoregulatory adaptations associated with nutrient ingestion and metabolite waste export, exposing complex host-parasite relationships in C. rogercresseyi. PMID:27016299

  1. Multifaceted roles of aquaporins as molecular conduits in plant responses to abiotic stresses.

    Science.gov (United States)

    Srivastava, Ashish Kumar; Penna, Suprasanna; Nguyen, Dong Van; Tran, Lam-Son Phan

    2016-06-01

    Abiotic stress has become a challenge to food security due to occurrences of climate change and environmental degradation. Plants initiate molecular, cellular and physiological changes to respond and adapt to various types of abiotic stress. Understanding of plant response mechanisms will aid in strategies aimed at improving stress tolerance in crop plants. One of the most common and early symptoms associated with these stresses is the disturbance in plant-water homeostasis, which is regulated by a group of proteins called "aquaporins". Aquaporins constitute a small family of proteins which are classified further on the basis of their localization, such as plasma membrane intrinsic proteins, tonoplast intrinsic proteins, nodulin26-like intrinsic proteins (initially identified in symbiosomes of legumes but also found in the plasma membrane and endoplasmic reticulum), small basic intrinsic proteins localized in ER (endoplasmic reticulum) and X intrinsic proteins present in plasma membrane. Apart from water, aquaporins are also known to transport CO2, H2O2, urea, ammonia, silicic acid, arsenite and wide range of small uncharged solutes. Besides, aquaporins also function to modulate abiotic stress-induced signaling. Such kind of versatile functions has made aquaporins a suitable candidate for development of transgenic plants with increased tolerance toward different abiotic stress. Toward this endeavor, the present review describes the versatile functions of aquaporins in water uptake, nutrient balancing, long-distance signal transfer, nutrient/heavy metal acquisition and seed development. Various functional genomic studies showing the potential of specific aquaporin isoforms for enhancing plant abiotic stress tolerance are summarized and future research directions are given to design stress-tolerant crops. PMID:25430890

  2. Water transport in brain:

    DEFF Research Database (Denmark)

    MacAulay, Nanna; Hamann, Steffan; Zeuthen, Thomas

    2004-01-01

    It is generally accepted that cotransporters transport water in addition to their normal substrates, although the precise mechanism is debated; both active and passive modes of transport have been suggested. The magnitude of the water flux mediated by cotransporters may well be significant: both...... the number of cotransporters per cell and the unit water permeability are high. For example, the Na(+)-glutamate cotransporter (EAAT1) has a unit water permeability one tenth of that of aquaporin (AQP) 1. Cotransporters are widely distributed in the brain and participate in several vital functions: inorganic......(+)-lactate cotransporters. We have previously determined water transport capacities for these cotransporters in model systems (Xenopus oocytes, cell cultures, and in vitro preparations), and will discuss their role in water homeostasis of the astroglial cell under both normo- and pathophysiologal situations. Astroglia...

  3. Localization of Reversion-Induced LIM Protein (RIL) in the Rat Central Nervous System

    International Nuclear Information System (INIS)

    Reversion-induced LIM protein (RIL) is a member of the ALP (actinin-associated LIM protein) subfamily of the PDZ/LIM protein family. RIL serves as an adaptor protein and seems to regulate cytoskeletons. Immunoblotting suggested that RIL is concentrated in the astrocytes in the central nervous system. We then examined the expression and localization of RIL in the rat central nervous system and compared it with that of water channel aquaporin 4 (AQP4). RIL was concentrated in the cells of ependyma lining the ventricles in the brain and the central canal in the spinal cord. In most parts of the central nervous system, RIL was expressed in the astrocytes that expressed AQP4. Double-labeling studies showed that RIL was concentrated in the cytoplasm of astrocytes where glial fibrillary acidic protein was enriched as well as in the AQP4-enriched regions such as the endfeet or glia limitans. RIL was also present in some neurons such as Purkinje cells in the cerebellum and some neurons in the brain stem. Differential expression of RIL suggests that it may be involved in the regulation of the central nervous system

  4. Interferon-γ suppresses intestinal epithelial aquaporin-1 expression via Janus kinase and STAT3 activation.

    Directory of Open Access Journals (Sweden)

    Michael S Dicay

    Full Text Available Inflammatory bowel diseases are associated with dysregulated electrolyte and water transport and resultant diarrhea. Aquaporins are transmembrane proteins that function as water channels in intestinal epithelial cells. We investigated the effect of the inflammatory cytokine, interferon-γ, which is a major player in inflammatory bowel diseases, on aquaporin-1 expression in a mouse colonic epithelial cell line, CMT93. CMT93 monolayers were exposed to 10 ng/mL interferon-γ and aquaporin-1 mRNA and protein expressions were measured by real-time PCR and western blot, respectively. In other experiments, CMT93 cells were pretreated with inhibitors or were transfected with siRNA to block the effects of Janus kinases, STATs 1 and 3, or interferon regulatory factor 2, prior to treatment with interferon-γ. Interferon-γ decreased aquaporin-1 expression in mouse intestinal epithelial cells in a manner that did not depend on the classical STAT1/JAK2/IRF-1 pathway, but rather, on an alternate Janus kinase (likely JAK1 as well as on STAT3. The pro-inflammatory cytokine, interferon-γ may contribute to diarrhea associated with intestinal inflammation in part through regulation of the epithelial aquaporin-1 water channel via a non-classical JAK/STAT receptor signalling pathway.

  5. A molecular modeling approach defines a new group of Nodulin 26-like aquaporins in plants

    International Nuclear Information System (INIS)

    The three-dimensional models built for the Nod26-like aquaporins all exhibit the typical α-helical fold of other aquaporins containing the two ar/R and NPA constriction filters along the central water channel. Besides these structural homologies, they readily differ with respect to the amino acid residues forming the ar/R selective filter. According to these discrepancies in both the hydrophilicity and pore size of the ar/R filter, Nod26-like aquaporins can be distributed in three subgroups corresponding to NIP-1, NIP-II and a third subgroup of Nod26-like aquaporins exhibiting a highly hydrophilic and widely open filter. However, all Nod26-like aquaporins display a bipartite distribution of electrostatic charges along the water channel with an electropositive extracellular vestibular portion followed by an electronegative cytosolic vestibular portion. The specific transport of water, non-ionic solutes (glycerol, urea, ammoniac), ions (NH4+) and gas (NH3) across the Nod26-like obviously depends on the electrostatic and conformational properties of their central water channel

  6. The aquaporin gene family of the ectomycorrhizal fungus Laccaria bicolor: lessons for symbiotic functions.

    Science.gov (United States)

    Dietz, Sandra; von Bülow, Julia; Beitz, Eric; Nehls, Uwe

    2011-06-01

    Soil humidity and bulk water transport are essential for nutrient mobilization. Ectomycorrhizal fungi, bridging soil and fine roots of woody plants, are capable of modulating both by being integrated into water movement driven by plant transpiration and the nocturnal hydraulic lift. Aquaporins are integral membrane proteins that function as gradient-driven water and/or solute channels. Seven aquaporins were identified in the genome of the ectomycorrhizal basidiomycete Laccaria bicolor and their role in fungal transfer processes was analyzed. Heterologous expression in Xenopus laevis oocytes revealed relevant water permeabilities for three aquaporins. In fungal mycelia, expression of the corresponding genes was high compared with other members of the gene family, indicating the significance of the respective proteins for plasma membrane water permeability. As growth temperature and ectomycorrhiza formation modified gene expression profiles of these water-conducting aquaporins, specific roles in those aspects of fungal physiology are suggested. Two aquaporins, which were highly expressed in ectomycorrhizas, conferred plasma membrane ammonia permeability in yeast. This indicates that these proteins are an integral part of ectomycorrhizal fungus-based plant nitrogen nutrition in symbiosis. PMID:21352231

  7. Use of Aquaporins to Achieve Needed Water Purity On ISS for the EMU Space Suit System

    Science.gov (United States)

    Hill, Terry; Taylor ,Brandon W.

    2012-01-01

    Use of Aquaporins to Achieve Needed Water Purity On ISS for the EMU Space Suit System. With the U.S. Space Shuttle fleet retired, the supply of extremely high-quality water "super-Q" - required for the EMU Space suit cooling on this ISS - will become a significant operational hardware challenge in the very near future. A proposed potential solution is the use of a filtration system consisting of a semi-permeable membrane embedded with aquaporin proteins. Aquaporins are a special class of trans-membrane proteins that facilitate passive transport of water and other substances across a membrane. The specificity of these proteins is such that only water is allowed through the protein structure, and this novel property invites their adaptation for use in water filtration systems, specifically usage on the ISS for the EMU space suit system. These proteins are found in many living systems and have been developed for commercial use today.

  8. Tubular localization and expressional dynamics of aquaporins in the kidney of seawater-challenged Atlantic salmon

    DEFF Research Database (Denmark)

    Engelund, Morten Buch; Madsen, Steffen S

    2015-01-01

    Most vertebrate nephrons possess an inherited ability to secrete fluid in normal or pathophysiological states. We hypothesized that renal aquaporin expression and localization are functionally regulated in response to seawater and during smoltification in Atlantic salmon and thus reflect a shift in...... renal function from filtration towards secretion. We localized aquaporins (Aqp) in Atlantic salmon renal tubular segments by immunohistochemistry and monitored their expressional dynamics using RT-PCR and immunoblotting. Three aquaporins: Aqpa1aa, Aqp1ab and Aqp8b and two aquaglyceroporins Aqp3a and Aqp....... Aqp10b was expressed apically and along the lateral membrane. Aqp8b was mainly basolateral and Aqp1ab was located in sub-apical intracellular compartments. mRNAs of aqp8b and aqp10b were higher in FW smolts compared to FW parr, whereas the opposite was true for aqp1aa. Aqp mRNA levels changed in...

  9. Crystal structure of a yeast aquaporin at 1.15 angstrom reveals a novel gating mechanism.

    Directory of Open Access Journals (Sweden)

    Gerhard Fischer

    2009-06-01

    Full Text Available Aquaporins are transmembrane proteins that facilitate the flow of water through cellular membranes. An unusual characteristic of yeast aquaporins is that they frequently contain an extended N terminus of unknown function. Here we present the X-ray structure of the yeast aquaporin Aqy1 from Pichia pastoris at 1.15 A resolution. Our crystal structure reveals that the water channel is closed by the N terminus, which arranges as a tightly wound helical bundle, with Tyr31 forming H-bond interactions to a water molecule within the pore and thereby occluding the channel entrance. Nevertheless, functional assays show that Aqy1 has appreciable water transport activity that aids survival during rapid freezing of P. pastoris. These findings establish that Aqy1 is a gated water channel. Mutational studies in combination with molecular dynamics simulations imply that gating may be regulated by a combination of phosphorylation and mechanosensitivity.

  10. Bidirectional water fluxes and specificity for small hydrophilic molecules in aquaporins 0-5

    DEFF Research Database (Denmark)

    Meinild, A K; Klærke, Dan Arne; Zeuthen, T

    1998-01-01

    for the osmotic water permeability (L p) were obtained in swelling as in shrinkage experiments demonstrating, for the first time, that aquaporins are bidirectional. The reflection coefficients (¿) of urea, glycerol, acetamide, and formamide at 23¿°C were: AQP0: 1, 1, 0.8, 0.6; AQP1: 1, 0.8, 1, 1; AQP2: 1, 0.8, 1......The dimensions of the aqueous pore in aquaporins (AQP) 0, 1, 2, 3, 4, and 5 expressed in Xenopus laevisoocytes were probed by comparing the ability of various solutes to generate osmotic flow. By improved techniques, volume flows were determined from initial rates of changes. Identical values...... and increased ¿glyc to 1 and ¿form to 0.6. We conclude that the pore of the various aquaporins are structurally different and that a simple steric model is insufficient to explain solute-pore interactions....

  11. Aquaporin-1 and aquaporin-3 expressions in the temporomandibular joint condylar cartilage after an experimentally induced osteoarthritis

    Institute of Scientific and Technical Information of China (English)

    MENG Juan-hong; MA Xu-chen; LI Zhi-min; WU Deng-cheng

    2007-01-01

    Background Over 70% of the total tissue weight in the cartilage matrix consists of water,and the early-stage osteoarthritic cartilage is characterized by swelling.Water transport in the cartilage matrix and across the membranes of chondrocytes may be important in normal and pathological conditions of cartilage.The purpose of this study was to identify aquaporin-1 (AQP1) and aquaporin-3 (AQP3) expressions in the mandibular condylar cartilage after experimentally induced osteoarthritis(OA)in rats.Methods An experimental temporomandibular joint OA was induced by partial discectomy in rats.The pathological characteristics of the normal,early-stage,and late-stage osteoarthritic TMJ cartilages were verified by histological techniques.The AQP1 and AQP3 gene expressions in the normal and osteoarthritic cartilages were measured using quantitative real-time reverse-transcription PCR analysis.The cartilage sections were incubated in primary polyclonal antibodies to AQP3;immunofluorescent microscopy was used to examine the AQP3 expression shown by its protein level.Results The mRNA expression levels of AQP1 and AQP3,analyzed using quantitative PCR,revealed that AQP3 mRNA was highly up-regulated in the OA cartilage,which was considered significant.There was no notable difference in the expression of AQP1 mRNA between OA and normal controls.With the progressing of the OA,the localization of the AQP3 protein was quite different from that of the normal cartilage.Cormpared to the normal cartilage,the expressions of AQP3 protein were observed mainly in the proliferative zone and the upper mid-zone chondrocytes at the early-stage of OA,and were observed to appear frequently throughout the mid-and deep zone during the late-stage of OA.Conclusions The high expression of AQP3 mRNA in the OA cartilage and the different localization of the AQP3 protein suggest that it may play a particular role in OA pathogenesis.Further study of AQP3 function may provide new insight into the

  12. Aquaporin-1 Expression in Proliferative Vitreoretinopathy and in Epiretinal Membranes

    Directory of Open Access Journals (Sweden)

    Elie Motulsky

    2014-01-01

    Full Text Available Purpose. Aquaporin-1 (AQP1 is involved in cell migration and proliferation; therefore, the purpose of the study was to investigate its expression in proliferative vitreoretinopathy (PVR and epiretinal membranes (ERM. Methods. 19 membranes from PVR and ERM were collected following eye surgery. AQP1 mRNA and protein expressions were determined by RT-qPCR and immunofluorescence in the membranes from PVR and ERM. Results. AQP1 mRNA and protein were expressed in both PVR and ERM as shown by RT-qPCR and immunofluorescence. AQP1 protein expression was heterogeneous among and between PVR and ERM and colocalized with alpha-smooth muscle actin (αSMA and with glial fibrillary acidic protein (GFAP. There were a higher percentage of cells coexpressing AQP1 and αSMA than AQP1 and GFAP. GFAP and αSMA did not colocalize. Conclusion. Our data show for the first time AQP1 expression in both PVR and ERM. AQP1 is expressed mostly by the αSMA-positive cells, presumably myofibroblasts, but also by GFAP-positive cells, assumed to be glial cells. These original findings warrant further functional investigations aiming at studying the potential role of AQP1 in cell migration and proliferation occurring during the development of PVR and ERM.

  13. Nuclear Receptor Regulation of Aquaporin-2 in the Kidney

    Science.gov (United States)

    Zhang, Xiao-Yan; Wang, Bing; Guan, You-Fei

    2016-01-01

    Aquaporin-2 (AQP2) is a vasopressin-regulated water channel responsible for regulating water reabsorption through the apical plasma membrane of the principal cells of renal collecting ducts. It has been found that dysregulation and dysfunction of AQP2 cause many disorders related to water balance in people and animals, including polyuria and dilutional hyponatremia. Classically, AQP2 mRNA and protein expression and its membrane translocation are regulated by systemic vasopressin involving short-term regulation of AQP2 trafficking to and from the apical plasma membrane and long-term regulation of the total amount of the AQP2 protein in the cell. Recently, increasing evidence has demonstrated that collecting duct AQP2 expression and membrane translocation are also under the control of many other local factors, especially nuclear receptors. Here, we briefly review the progress of studies in this area and discuss the role of nuclear receptors in the regulation of water reabsorption via affecting AQP2 expression and function. PMID:27409611

  14. Diabetes Insipidus in Mice with a Mutation in Aquaporin-2.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available Congenital nephrogenic diabetes insipidus (NDI is a disease characterized by failure of the kidney to concentrate urine in response to vasopressin. Human kindreds with nephrogenic diabetes insipidus have been found to harbor mutations in the vasopressin receptor 2 (Avpr2 gene or the vasopressin-sensitive water channel aquaporin-2 (Aqp2 gene. Development of a treatment is rendered difficult due to the lack of a viable animal model. Through forward genetic screening of ethylnitrosourea-mutagenized mice, we report the identification and characterization of a mouse model of NDI, with an F204V mutation in the Aqp2 gene. Unlike previously attempted murine models of NDI, our mice survive to adulthood and more exactly recapitulate the human disorder. Previous in vitro experiments using renal cell lines suggest recessive Aqp2 mutations result in improper trafficking of the mutant water pore. Using these animals, we have directly proven this hypothesis of improper AQP2 translocation as the molecular defect in nephrogenic diabetes insipidus in the intact organism. Additionally, using a renal cell line we show that the mutated protein, AQP2-F204V, is retained in the endoplasmic reticulum and that this abnormal localization can be rescued by wild-type protein. This novel mouse model allows for further mechanistic studies as well as testing of pharmacological and gene therapies for NDI.

  15. Whole gene family expression and drought stress regulation of aquaporins.

    Science.gov (United States)

    Alexandersson, Erik; Fraysse, Laure; Sjövall-Larsen, Sara; Gustavsson, Sofia; Fellert, Maria; Karlsson, Maria; Johanson, Urban; Kjellbom, Per

    2005-10-01

    Since many aquaporins (AQPs) act as water channels, they are thought to play an important role in plant water relations. It is therefore of interest to study the expression patterns of AQP isoforms in order to further elucidate their involvement in plant water transport. We have monitored the expression patterns of all 35 Arabidopsis AQPs in leaves, roots and flowers by cDNA microarrays, specially designed for AQPs, and by quantitative real-time reverse transcriptase PCR (Q-RT-PCR). This showed that many AQPs are pre-dominantly expressed in either root or flower organs, whereas no AQP isoform seem to be leaf specific. Looking at the AQP subfamilies, most plasma membrane intrinsic proteins (PIPs) and some tonoplast intrinsic proteins (TIPs) have a high level of expression, while NOD26-like proteins (NIPs) are present at a much lower level. In addition, we show that PIP transcripts are generally down-regulated upon gradual drought stress in leaves, with the exception of AtPIP1;4 and AtPIP2;5, which are up-regulated. AtPIP2;6 and AtSIP1;1 are constitutively expressed and not significantly affected by the drought stress. The transcriptional down-regulation of PIP genes upon drought stress could also be observed on the protein level. PMID:16235111

  16. Aquaporin 11 in the developing mouse submandibular gland.

    Science.gov (United States)

    Larsen, Helga S; Ruus, Ann-Kristin; Schreurs, Olav; Galtung, Hilde Kanli

    2010-02-01

    Several aquaporins (AQPs) have been detected in mature and embryonic mammalian salivary glands (AQP1 and AQP3-AQP8). However, AQP11 has, to our knowledge, never before been described in salivary glands, but is known to be important in, for example, kidney development in mice. We therefore thought it relevant to investigate if AQP11 was present during salivary organogenesis. The submandibular salivary gland (SMG) from CD1 mice was studied during prenatal development and early postnatal development, and also in young adult male and female mice. The expression trend of the AQP11 transcript was detected using the reverse transcription-polymerase chain reaction (RT-PCR), and the temporal-spatial pattern was observed using in situ hybridization. The AQP11 transcript was first detected at embryonic day 13.5 and showed a more or less constitutive expression trend during the prenatal and early postnatal SMG development. Spatial studies demonstrated that the AQP11 transcript was present in the developing and mature duct structures at all stages studied. In the end pieces, the AQP11 transcript was reduced during glandular development. Our results point to an important role for AQP11 during salivary gland development. PMID:20156259

  17. A molecular understanding of the dynamic mechanism of aquaporin osmosis

    CERN Document Server

    Shua, Liangsuo; Qian, Xin; Wanga, Xiyun; Lin, Yixin; Tan, Kai; Shu, Chaohui; Jin, Shiping

    2014-01-01

    AQPs (aquaporins), the rapid water channels of cells, play a key role in maintaining osmotic equilibrium of cells. In this paper, we reported the dynamic mechanism of AQP osmosis at the molecular level. A theoretical model based on molecular dynamics was carried out and verified by the published experimental data. The reflection coefficients ({\\sigma}) of neutral molecules are mainly decided by their relative size with AQPs, and increase with a third power up to a constant value 1. This model also indicated that the reflection coefficient of a complete impermeable solute can be smaller than 1. The H+ concentration of solution can influence the driving force of the AQPs by changing the equivalent diameters of vestibules surrounded by loops with abundant polar amino acids. In this way, pH of solution can regulate water permeability of AQPs. Therefore, an AQP may not only work as a switch to open or close, but as a rapid response molecular valve to control its water flow. The vestibules can prevent the channel b...

  18. The three-dimensional structure of aquaporin-1

    Science.gov (United States)

    Walz, Thomas; Hirai, Teruhisa; Murata, Kazuyoshi; Heymann, J. Bernard; Mitsuoka, Kaoru; Fujiyoshi, Yoshinori; Smith, Barbara L.; Agre, Peter; Engel, Andreas

    1997-06-01

    The entry and exit of water from cells is a fundamental process of life. Recognition of the high water permeability of red blood cells led to the proposal that specialized water pores exist in the plasma membrane. Expression in Xenopus oocytes and functional studies of an erythrocyte integral membrane protein of relative molecular mass 28,000, identified it as the mercury-sensitive water channel, aquaporin-1 (AQP1). Many related proteins, all belonging to the major intrinsic protein (MIP) family, are found throughout nature. AQP1 is a homotetramer containing four independent aqueous channels. When reconstituted into lipid bilayers, the protein forms two-dimensional lattices with a unit cell containing two tetramers in opposite orientation. Here we present the three-dimensional structure of AQP1 determined at 6Å resolution by cryo-electron microscopy. Each AQP1 monomer has six tilted, bilayer-spanning α-helices which form a right-handed bundle surrounding a central density. These results, together with functional studies, provide a model that identifies the aqueous pore in the AQP1 molecule and indicates the organization of the tetrameric complex in the membrane.

  19. Hepatocyte and Sertoli Cell Aquaporins, Recent Advances and Research Trends

    Directory of Open Access Journals (Sweden)

    Raquel L. Bernardino

    2016-07-01

    Full Text Available Aquaporins (AQPs are proteinaceous channels widespread in nature where they allow facilitated permeation of water and uncharged through cellular membranes. AQPs play a number of important roles in both health and disease. This review focuses on the most recent advances and research trends regarding the expression and modulation, as well as physiological and pathophysiological functions of AQPs in hepatocytes and Sertoli cells (SCs. Besides their involvement in bile formation, hepatocyte AQPs are involved in maintaining energy balance acting in hepatic gluconeogenesis and lipid metabolism, and in critical processes such as ammonia detoxification and mitochondrial output of hydrogen peroxide. Roles are played in clinical disorders including fatty liver disease, diabetes, obesity, cholestasis, hepatic cirrhosis and hepatocarcinoma. In the seminiferous tubules, particularly in SCs, AQPs are also widely expressed and seem to be implicated in the various stages of spermatogenesis. Like in hepatocytes, AQPs may be involved in maintaining energy homeostasis in these cells and have a major role in the metabolic cooperation established in the testicular tissue. Altogether, this information represents the mainstay of current and future investigation in an expanding field.

  20. Recombinant Production of Human Aquaporin-1 to an Exceptional High Membrane Density in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Bomholt, Julie; Helix Nielsen, Claus; Scharff-Poulsen, Peter;

    2013-01-01

    In the present paper we explored the capacity of yeast Saccharomyces cerevisiae as host for heterologous expression of human Aquaporin-1. Aquaporin-1 cDNA was expressed from a galactose inducible promoter situated on a plasmid with an adjustable copy number. Human Aquaporin-1 was C-terminally tag......In the present paper we explored the capacity of yeast Saccharomyces cerevisiae as host for heterologous expression of human Aquaporin-1. Aquaporin-1 cDNA was expressed from a galactose inducible promoter situated on a plasmid with an adjustable copy number. Human Aquaporin-1 was C......-terminally tagged with yeast enhanced GFP for quantification of functional expression, determination of sub-cellular localization, estimation of in vivo folding efficiency and establishment of a purification protocol. Aquaporin-1 was found to constitute 8.5 percent of total membrane protein content after expression...

  1. Incipient balancing selection through adaptive loss of aquaporins in natural Saccharomyces cerevisiae populations.

    Directory of Open Access Journals (Sweden)

    Jessica L Will

    2010-04-01

    Full Text Available A major goal in evolutionary biology is to understand how adaptive evolution has influenced natural variation, but identifying loci subject to positive selection has been a challenge. Here we present the adaptive loss of a pair of paralogous genes in specific Saccharomyces cerevisiae subpopulations. We mapped natural variation in freeze-thaw tolerance to two water transporters, AQY1 and AQY2, previously implicated in freeze-thaw survival. However, whereas freeze-thaw-tolerant strains harbor functional aquaporin genes, the set of sensitive strains lost aquaporin function at least 6 independent times. Several genomic signatures at AQY1 and/or AQY2 reveal low variation surrounding these loci within strains of the same haplotype, but high variation between strain groups. This is consistent with recent adaptive loss of aquaporins in subgroups of strains, leading to incipient balancing selection. We show that, although aquaporins are critical for surviving freeze-thaw stress, loss of both genes provides a major fitness advantage on high-sugar substrates common to many strains' natural niche. Strikingly, strains with non-functional alleles have also lost the ancestral requirement for aquaporins during spore formation. Thus, the antagonistic effect of aquaporin function-providing an advantage in freeze-thaw tolerance but a fitness defect for growth in high-sugar environments-contributes to the maintenance of both functional and nonfunctional alleles in S. cerevisiae. This work also shows that gene loss through multiple missense and nonsense mutations, hallmarks of pseudogenization presumed to emerge after loss of constraint, can arise through positive selection.

  2. Expression and Function of the Nicotiana tabacum Aquaporin NtAQP1

    OpenAIRE

    Siefritz, Franka

    2002-01-01

    Die vorliegende Arbeit zeigt die Korrelation zwischen räumlichem und zeitlichem Expressionsmuster von dem Aquaporin NtAQP1 und seiner Funktion im Wasserhaushalt in planta. Immunologische in situ-Studien deuteten auf eine NtAQP1-Protein-Akkumulation in der Wurzelexodermis und -endodermis, im Cortex, in der Nähe der Leitbündel, im Xylemparenchym und in Zellen der Atemhöhle hin. Das Aquaporin wurde auch in longitudinalen Zellreihen der Petiolen in erhöhten Mengen gefunden. Expressionsstudien mit...

  3. Galactorrhea in a Patient With Aquaporin-4 Antibody-positive Neuromyelitis Optica Spectrum Disorder: A Case Report and Review of the Literature.

    Science.gov (United States)

    Watanabe, Masahiko; Furusho, Kentaro; Takahashi, Toshiyuki; Tamaoka, Akira

    2015-12-01

    This is the first report of a case of galactorrhea in a patient with neuromyelitis optica spectrum disorder (NMOSD) diagnosed on the basis of antiaquaporin-4 antibody seropositivity. The hypothalamus is becoming known as an area highly expressing aquaporin-4 and frequently involved in intracranial lesions of patients with neuromyelitis optica (NMO). We reviewed cases of hypothalamic endocrinopathy among patients with NMO, NMOSD, and the Japanese opticospinal form of MS. Among these cases, galactorrhea was the second most common symptom. Signs of hypothalamic endocrinopathies may be obscured by the grave neurological deficits caused by NMO. We recommend paying special attention to hypothalamic endocrinopathies among patients with NMO or NMOSD, irrespective of brain MRI findings. PMID:26671741

  4. [A case of anti-aquaporin 4 antibody-positive Sjögren syndrome associated with a relapsed myelitis in pregnancy].

    Science.gov (United States)

    Tsugawa, Jun; Tsuboi, Yoshio; Inoue, Hirosato; Baba, Yasuhiko; Yamada, Tatsuo

    2010-01-01

    It is known that pregnancy influences the relapsing rate of multiple sclerosis (MS); however, interaction between pregnancy and relapse of neuromyelitis optica (NMO), a distinct disease from MS, remains unclear. A 34-year-old woman who 1 year previously had clinical history of Sjögren syndrome complicated by myelitis with the presence of anti-AQP4 antibody in her serum, although there was no optic neuritis involvement, was neurologically normal at time of becoming pregnant. In the 22nd week of her pregnancy, however, she developed abdominal belt-shaped numbness and sensory impairment followed by weakness of bilateral lower limb leading to difficulty of her gait. MR imaging revealed hyperintense lesions within the spinal cord extending from C2 to T2 vertebral level with marked spinal cord swelling, indicating relapse of myelitis associated with anti-AQP4 antibody. She was treated with intravenous corticosteroid with marked benefits for her neurological status; she was able to walk without assistance after the treatment. However, in the 30th week she relapsed with myelitis at T2 to T9 vertebral level on MR imaging. Intravenous steroid administration again elicited improvement. She delivered a baby via Caesarean section at 34 weeks of pregnancy. After delivery, she started taking oral corticosteroid as preventive therapy for further relapse of myelitis; thus far she has had no relapse at 7 months of follow-up. There are few reports regarding the influence of pregnancy on anti-AQP4 antibody-positive myelitis. Although further investigation should be done to clarify the difference of immunological changes during pregnancy between NMO and conventional MS, our case together with previous reports indicate increased risk of relapse during pregnancy in NMO. It is necessary to remain vigilant against possible risk of relapse during pregnancy in patients with NMO and/or positive anti-AQP4 antibody. Intravenous steroid administration seems safe and effective against relapse of

  5. Expression of aquaporins in intestine after heat stroke.

    Science.gov (United States)

    Wang, Yuan-Hung; Liu, Tsung-Ta; Kung, Woon-Man; Chen, Chun-Chi; Wen, Ya-Ting; Lin, I-Chan; Huang, Chi-Chang; Wei, Li

    2015-01-01

    Heat stroke (HS) has been shown to induce intestinal barrier dysfunction during whole body hyperthermia. HS-induced intestinal permeability change may result from modulation of aquaporin (AQP) expression, which subsequently regulates water homeostasis. This study aimed to evaluate AQP expression in the intestine of rats with HS at different recovery time points. Sprague-Dawley (SD) rats were exposed to an ambient temperature of 40 ± 0.5°C until a maximum core temperature of 40.5°C was attained. The small intestine was surgically removed and histologically examined, and AQP expression was determined by reverse transcription polymerase chain reaction and immunohistochemical staining. H&E staining revealed those intestinal villi were destroyed from HS0 to HS1 and rebuilt from HS3 to HS12. We further stain with activated caspase 3 found expressed at HS0 and back to normal at HS3. Investigation of AQP mRNA expression identified 10 genes. PCR results of AQP1, 3, 7, 8, and 11 transcripts were significantly higher in the HS group than in the sham group. Immunohistochemical staining showed a more than 11-fold increase in AQP3 and 11 expressions at HS0. AQP1 and 8 increased at HS1 and AQP7 increased at HS3 compared with those in the sham group. In this study, we found HS induced jejunum damage and cell apoptosis. AQPs were upregulation/downregulation after HS in different time point suggested that water/glycerol transport was important when hyperthermia occurred. Furthermore, the biological function of the AQP needs more exploration in response to HS. PMID:26464618

  6. Pores in the epidermis: aquaporins and tight junctions.

    Science.gov (United States)

    Brandner, J M

    2007-12-01

    Water homeostasis of the epidermis is important for the appearance and physical properties of the skin, as well as for water balance in the body. It depends on several factors, e.g. barrier quality, uptake of water into the epidermis, concentration of water-retaining humectants, and external humidity. Aquaporins (AQPs) are pores in the plasmamembranes of cells. Monomeric AQPs form barrel-like structures that are primarily water selective, some AQPs also transport glycerol and possibly other small solutes. In the epidermis, AQP3 is the predominant AQP. It is localized mainly in basal but also in suprabasal layers of the epidermis and is permeable for water as well as for glycerol, a humectant. Mice deficient in AQP3 exhibit reduced stratum corneum (SC) hydration and impaired SC barrier recovery after SC removal. In skin diseases associated with elevated transepidermal water loss (TEWL) and reduced SC hydration, altered expression of AQP3 was shown. Tight junctions (TJ) are cell-cell junctions, which play a central role in sealing the intercellular space of cell sheets and thereby establishing a paracellular barrier. Within the TJ, pores are postulated to exist, which allow the controlled diffusion of water and solutes via the paracellular pathway. In the epidermis, TJ structures were demonstrated in the stratum granulosum whereas TJ proteins were found in all viable layers. Mice which overexpress or are deficient of key-proteins of TJ die soon after birth because of a tremendous TEWL. In various skin diseases that are accompanied by elevated TEWL and reduced skin hydration, staining patterns of TJ proteins are altered. This review will summarize our current knowledge of the involvement of AQPs and TJ in the water homeostasis of the epidermis. PMID:18489380

  7. Effects of proteoliposome composition and draw solution types on separation performance of aquaporin-based proteoliposomes: implications for seawater desalination using aquaporin-based biomimetic membranes.

    Science.gov (United States)

    Zhao, Yang; Vararattanavech, Ardcharaporn; Li, Xuesong; Hélixnielsen, Claus; Vissing, Thomas; Torres, Jaume; Wang, Rong; Fane, Anthony G; Tang, Chuyang Y

    2013-02-01

    Aquaporins are a large family of water transport proteins in cell membranes. Their high water permeability and solute rejection make them potential building blocks for high-performance biomimetic membranes for desalination. In the current study, proteoliposomes were prepared using AquaporinZ from Escherichia coli cells, and their separation properties were characterized by stopped-flow measurements. The current study systematically investigated the effect of proteoliposome composition (lipid type, protein-to-lipid ratio (PLR), and the addition of cholesterol) on water permeability and NaCl retention. Among the various lipids investigated, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)-based proteoliposomes were found to have excellent osmotic water permeability and NaCl reflection coefficient values. Increasing the PLR of DOPC proteoliposomes up to 1:200 increased their osmotic water permeability. However, further increase in the PLR reduced the osmotic water permeability probably due to the occurrence of defects in the proteoliposomes, whereas the addition of cholesterol improved their osmotic water permeation likely due to defects sealing. The current study also investigated the effect of major dissolved ions in seawater (e.g., Mg(2+) and SO(4)(2-)) on the stability of proteoliposomes, and design criteria for aquaporin-based biomimetic membranes are proposed in the context of desalination. PMID:23311686

  8. Root ABA Accumulation Enhances Rice Seedling Drought Tolerance under Ammonium Supply: Interaction with Aquaporins

    Science.gov (United States)

    Ding, Lei; Li, Yingrui; Wang, Ying; Gao, Limin; Wang, Min; Chaumont, François; Shen, Qirong; Guo, Shiwei

    2016-01-01

    In previous studies, we demonstrated that ammonium nutrition enhances the drought tolerance of rice seedlings compared to nitrate nutrition and contributes to a higher root water uptake ability. It remains unclear why rice seedlings maintain a higher water uptake ability when supplied with ammonium under drought stress. Here, we focused on the effects of nitrogen form and drought stress on root abscisic acid (ABA) concentration and aquaporin expression using hydroponics experiments and stimulating drought stress with 10% PEG6000. Drought stress decreased the leaf photosynthetic rate and stomatal conductivity and increased the leaf temperature of plants supplied with either ammonium or nitrate, but especially under nitrate supply. After 4 h of PEG treatment, the root protoplast water permeability and the expression of root PIP and TIP genes decreased in plants supplied with ammonium or nitrate. After 24 h of PEG treatment, the root hydraulic conductivity, the protoplast water permeability, and the expression of some aquaporin genes increased in plants supplied with ammonium compared to those under non-PEG treatment. Root ABA accumulation was induced by 24 h of PEG treatment, especially in plants supplied with ammonium. The addition of exogenous ABA decreased the expression of PIP and TIP genes under non-PEG treatment but increased the expression of some of them under PEG treatment. We concluded that drought stress induced a down-regulation of aquaporin expression, which appeared earlier than did root ABA accumulation. With continued drought stress, aquaporin expression and activity increased due to root ABA accumulation in plants supplied with ammonium.

  9. Requirement for asparagine in the aquaporin NPA sequence signature motifs for cation exclusion

    DEFF Research Database (Denmark)

    Wree, Dorothea; Wu, Binghua; Zeuthen, Thomas;

    2011-01-01

    Two highly conserved NPA motifs are a hallmark of the aquaporin (AQP) family. The NPA triplets form N-terminal helix capping structures with the Asn side chains located in the centre of the water or solute-conducting channel, and are considered to play an important role in AQP selectivity. Althou...

  10. Demeclocycline Attenuates Hyponatremia by Reducing Aquaporin-2 Expression in the Renal Inner Medulla

    DEFF Research Database (Denmark)

    Kortenoeven, Marleen L. A.; Sinke, Anne P.; Hadrup, Niels;

    2013-01-01

    Binding of vasopressin to its type-2 receptor in renal collecting ducts induces cAMP signaling, transcription and translocation of aquaporin-2 (AQP2) water channels to the plasma membrane and water reabsorption from the pro-urine. Demeclocycline is currently used to treat hyponatremia in patients...

  11. Enhancement of proton conductance by mutations of the selectivity filter of aquaporin-1

    DEFF Research Database (Denmark)

    Li, Hui; Chen, Hanning; Steinbronn, Christina; Wu, Binghua; Beitz, Eric; Zeuthen, Thomas; Voth, Gregory A

    2011-01-01

    Prevention of cation permeation in wild-type aquaporin-1 (AQP1) is believed to be associated with the Asn-Pro-Ala (NPA) region and the aromatic/arginine selectivity filter (SF) domain. Previous work has suggested that the NPA region helps to impede proton permeation due to the protein backbone co...

  12. Putative role of aquaporins in variable hydraulic conductance of leaves in response to light.

    Science.gov (United States)

    Cochard, Hervé; Venisse, Jean-Stéphane; Barigah, Têtè Sévérien; Brunel, Nicole; Herbette, Stéphane; Guilliot, Agnès; Tyree, Melvin T; Sakr, Soulaiman

    2007-01-01

    Molecular and physiological studies in walnut (Juglans regia) are combined to establish the putative role of leaf plasma membrane aquaporins in the response of leaf hydraulic conductance (K(leaf)) to irradiance. The effects of light and temperature on K(leaf) are described. Under dark conditions, K(leaf) was low, but increased by 400% upon exposure to light. In contrast to dark conditions, K(leaf) values of light-exposed leaves responded to temperature and 0.1 mm cycloheximide treatments. Furthermore, K(leaf) was not related to stomatal aperture. Data of real-time reverse transcription-polymerase chain reaction showed that K(leaf) dynamics were tightly correlated with the transcript abundance of two walnut aquaporins (JrPIP2,1 and JrPIP2,2). Low K(leaf) in the dark was associated with down-regulation, whereas high K(leaf) in the light was associated with up-regulation of JrPIP2. Light responses of K(leaf) and aquaporin transcripts were reversible and inhibited by cycloheximide, indicating the importance of de novo protein biosynthesis in this process. Our results indicate that walnut leaves can rapidly change their hydraulic conductance and suggest that these changes can be explained by regulation of plasma membrane aquaporins. Model simulation suggests that variable leaf hydraulic conductance in walnut might enhance leaf gas exchanges while buffering leaf water status in response to ambient light fluctuations. PMID:17114274

  13. High-resolution x-ray structure of human aquaporin 5

    NARCIS (Netherlands)

    Horsefield, Rob; Nordén, Kristina; Fellert, Maria; Backmark, Anna; Törnroth-Horsefield, Susanna; Terwisscha van Scheltinga, Anke C.; Kvassman, Jan; Kjellbom, Per; Johanson, Urban; Neutze, Richard

    2008-01-01

    Human aquaporin 5 (HsAQP5) facilitates the transport of water across plasma membranes and has been identified within cells of the stomach, duodenum, pancreas, airways, lungs, salivary glands, sweat glands, eyes, lacrimal glands, and the inner ear. AQP5, like AQP2, is subject to posttranslational reg

  14. NH3 and NH4+ permeability in aquaporin-expressing Xenopus oocytes

    DEFF Research Database (Denmark)

    Holm, Lars M.; Jahn, Thomas Paul; Møller, Anders Laurell Blom;

    2005-01-01

    We have shown recently, in a yeast expression system, that some aquaporins are permeable to ammonia. In the present study, we expressed the mammalian aquaporins AQP8, AQQP9, AQP3, AQP1 and a plant aquaporin TIP2;1 in Xenopus oocytes to study the transport of ammonia (NH3) and ammonium (NH4+) under...... opencircuit and voltage-clamped conditions. TIP2;1 was tested as the wild-type and in a mutated version (tip2;1) in which the water permeability is intact. When AQP8-, AQP9-, AQP3- and TIP2;1-expressing oocytes were placed in a well-stirred bathing medium of low buffer capacity, NH3 permeability was evident...... oocytes as well as AQP1 and tip2;1-expressing oocytes showed small currents that were associated with small and even negative volume changes. We conclude that AQP8, AQP9, AQP3, and TIP2;1, apart from being water channels, also support significant fluxes of NH3. These aquaporins could support NH4...

  15. Aquaporin-1 Expression in Retinal Pigment Epithelial Cells Overlying Retinal Drusen

    DEFF Research Database (Denmark)

    Tran, Thuy Linh; Bek, Toke; la Cour, Morten;

    2016-01-01

    PURPOSE: In the outer retina, age-related macular degeneration (AMD) results in reduced hydraulic conductivity in Bruch's membrane, possibly leading to altered water transport in retinal pigment epithelial (RPE) cells. We hypothesize that RPE cells may express aquaporin-1 (AQP1) to compensate for...

  16. Gene interference regulates aquaporin-4 expression in swollen tissue of rats with cerebral ischemic edema Correlation with variation in apparent diffusion coefficient

    Institute of Scientific and Technical Information of China (English)

    Hui Hu; Hong Lu; Zhanping He; Xiangjun Han; Jing Chen; Rong Tu

    2012-01-01

    To investigate the effects of mRNA interference on aquaporin-4 expression in swollen tissue of rats with ischemic cerebral edema, and diagnose the significance of diffusion-weighted MRI, we injected 5 μL shRNA- aquaporin-4 (control group) or siRNA- aquaporin-4 solution (1:800) (RNA interference group) into the rat right basal ganglia immediately before occlusion of the middle cerebral artery. At 0.25 hours after occlusion of the middle cerebral artery, diffusion-weighted MRI displayed a high signal; within 2 hours, the relative apparent diffusion coefficient decreased markedly, aquaporin-4 expression increased rapidly, and intracellular edema was obviously aggravated; at 4 and 6 hours, the relative apparent diffusion coefficient slowly returned to control levels, aquaporin-4 expression slightly increased, and angioedema was observed. In the RNA interference group, during 0.25- 6 hours after injection of siRNA- aquaporin-4 solution, the relative apparent diffusion coefficient slightly fluctuated and aquaporin-4 expression was upregulated; during 0.5-4 hours, the relative apparent diffusion coefficient was significantly higher, while aquaporin-4 expression was significantly lower when compared with the control group, and intracellular edema was markedly reduced; at 0.25 and 6 hours, the relative apparent diffusion coefficient and aquaporin-4 expression were similar when compared with the control group; obvious angioedema remained at 6 hours. Pearson's correlation test results showed that aquaporin-4 expression was negatively correlated with the apparent diffusion coefficient (r = -0.806, P < 0.01). These findings suggest that upregulated aquaporin-4 expression is likely to be the main molecular mechanism of intracellular edema and may be the molecular basis for decreased relative apparent diffusion coefficient. Aquaporin-4 gene interference can effectively inhibit the upregulation of aquaporin-4 expression during the stage of intracellular edema with time

  17. Two putative-aquaporin genes are differentially expressed during arbuscular mycorrhizal symbiosis in Lotus japonicus

    Directory of Open Access Journals (Sweden)

    Giovannetti Marco

    2012-10-01

    Full Text Available Abstract Background Arbuscular mycorrhizas (AM are widespread symbioses that provide great advantages to the plant, improving its nutritional status and allowing the fungus to complete its life cycle. Nevertheless, molecular mechanisms that lead to the development of AM symbiosis are not yet fully deciphered. Here, we have focused on two putative aquaporin genes, LjNIP1 and LjXIP1, which resulted to be upregulated in a transcriptomic analysis performed on mycorrhizal roots of Lotus japonicus. Results A phylogenetic analysis has shown that the two putative aquaporins belong to different functional families: NIPs and XIPs. Transcriptomic experiments have shown the independence of their expression from their nutritional status but also a close correlation with mycorrhizal and rhizobial interaction. Further transcript quantification has revealed a good correlation between the expression of one of them, LjNIP1, and LjPT4, the phosphate transporter which is considered a marker gene for mycorrhizal functionality. By using laser microdissection, we have demonstrated that one of the two genes, LjNIP1, is expressed exclusively in arbuscule-containing cells. LjNIP1, in agreement with its putative role as an aquaporin, is capable of transferring water when expressed in yeast protoplasts. Confocal analysis have demonstrated that eGFP-LjNIP1, under its endogenous promoter, accumulates in the inner membrane system of arbusculated cells. Conclusions Overall, the results have shown different functionality and expression specificity of two mycorrhiza-inducible aquaporins in L. japonicus. One of them, LjNIP1 can be considered a novel molecular marker of mycorrhizal status at different developmental stages of the arbuscule. At the same time, LjXIP1 results to be the first XIP family aquaporin to be transcriptionally regulated during symbiosis.

  18. Rhubarb Tannins Extract Inhibits the Expression of Aquaporins 2 and 3 in Magnesium Sulphate-Induced Diarrhoea Model

    OpenAIRE

    Chunfang Liu; Yanfang Zheng; Wen Xu; Hui Wang; Na Lin

    2014-01-01

    Tannins, a group of major active components of Chinese rhubarb and widely distributed in nature, have a significant antidiarrhoeal activity. Aquaporins (AQPs) 2 and 3 play important roles in regulating water transfer during diarrhoea. The present study aims to determine the effect of the total tannins extract of rhubarb on aquaporins (AQPs) 2 and 3 in diarrhoea mice and HT-29 cells both induced by magnesium sulphate (MgSO4). Our results showed that rhubarb tannins extract (RTE) significantly ...

  19. The relationship between root hydraulics and scion vigour across Vitis rootstocks: what role do root aquaporins play?

    OpenAIRE

    GAMBETTA, G. A.; Manuck, C. M.; Drucker, S. T.; Shaghasi, T.; Fort, K.; Matthews, M A; Walker, M. A.; McElrone, A. J.

    2012-01-01

    Vitis vinifera scions are commonly grafted onto rootstocks of other grape species to influence scion vigour and provide resistance to soil-borne pests and abiotic stress; however, the mechanisms by which rootstocks affect scion physiology remain unknown. This study characterized the hydraulic physiology of Vitis rootstocks that vary in vigour classification by investigating aquaporin (VvPIP) gene expression, fine-root hydraulic conductivity (Lp r ), % aquaporin contribution to Lp r , scion tr...

  20. Expression of Fragaria vesca PIP Aquaporins in Response to Drought Stress: PIP Down-Regulation Correlates with the Decline in Substrate Moisture Content

    OpenAIRE

    Šurbanovski, Nada; Sargent, Daniel J.; Else, Mark A.; Simpson, David W; Zhang, Hanma; Grant, Olga M.

    2013-01-01

    PIP aquaporin responses to drought stress can vary considerably depending on the isoform, tissue, species or level of stress; however, a general down-regulation of these genes is thought to help reduce water loss and prevent backflow of water to the drying soil. It has been suggested therefore, that it may be necessary for the plant to limit aquaporin production during drought stress, but it is unknown whether aquaporin down-regulation is gradual or triggered by a particular intensity of the ...

  1. The response of Arabidopsis root water transport to a challenging environment implicates reactive oxygen species- and phosphorylation-dependent internalization of aquaporins

    OpenAIRE

    Boursiac, Yann; Prak, Sodana; Boudet, Julie; Postaire, Olivier; Luu, Doan-Trung; Tournaire-Roux, Colette; Santoni, Véronique; Maurel, Christophe

    2008-01-01

    Aquaporins, which facilitate the diffusion of water across biological membranes, are key molecules for the regulation of water transport at the cell and organ levels. We recently reported that hydrogen peroxide (H2O2) acts as an intermediate in the regulation of Arabidopsis root water transport and aquaporins in response to NaCl and salicylic acid (SA).1 Its action involves signaling pathways and an internalization of aquaporins from the cell surface. The present addendum connects these findi...

  2. Effect of Dexamethasone and Aquaporin-1 Antisense Oligonucleotides on the Aquaporin-1 Expression in Cultured Human Trabecular Meshwork Cells

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The changes in the expression of aquaporin-1 (AQP1) mRNA and protein in cultured human trabecular meshwork (HTM) cells treated with dexamethasone and transfected with antisense oligonucleotides (AS-ODN) were studied, and the implication of AQP1 regulation in corticosteroid-glaucoma and the possibility of AS-ODN inhibiting the AQP1 expression were evaluated.The cultured HTM cells in vitro were treated with different concentrations of dexamethasone and transfected with oligonucleotides for 5 days respectively. Then, total RNA and protein of HTM cells were extracted. The changes of AQP1 mRNA and protein were demonstrated qualitatively and quantitatively by RT-PCR and Western blot. Band intensities were detected by imaging analysis.There was a parallel relationship between the results of RT-PCR and those of Western blot. The expression levels of AQP1 mRNA and protein in dexamethasone-treated groups were increased initially and decreased later as dexamethasone concentration was stepped up. In the 0.04 μg/mL and 0.4 μg/mL groups, the levels of AQP1 were higher than in control group (0μg/mL). In the 4μg/mL and 40μg/mL groups, the AQP1 expression levels were lower than in control group. AS-ODN could down-regulate the expression of AQP1 mRNA and protein in a dose-dependent manner. At 5 μg/mL, down-regulation efficiency reached the maximum. There was no statistically significant difference in the expression of AQP1 mRNA and protein between all sense oligonucleotides groups and control group. It was suggested that dexamethasone may induce the changes of the AQP1 expression in HTM cells to be involved in the occurrence of corticosteroid-glaucoma. AS-ODN can down-regulate the AQP1 expression in HTM cells to some extent.

  3. Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gang, QiangQiang, E-mail: rousikang@163.com; Zhang, Jianing, E-mail: 1325916060@qq.com; Hao, Peng, E-mail: 1043600590@qq.com; Xu, Yikai, E-mail: yikaivip@163.com

    2013-11-01

    Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy.

  4. Detection of hypoxic-ischemic brain injury with 3D-enhanced T2* weighted angiography (ESWAN) imaging

    International Nuclear Information System (INIS)

    Objective: To demonstrate the use of 3D-enhanced T2* weighted angiography (ESWAN) imaging for the observation and quantification of the evolution of brain injury induced by a recently developed model of hypoxic-ischemic brain injury (HI/R) in neonatal piglets. Methods: For these experiments, newborn piglets were subjected to HI/R injury, during which ESWAN scanning was performed, followed by H and E staining and immunohistochemistry of AQP-4 expression. Results: In the striatum, values from T2* weighted magnetic resonance imaging (MRI) increased and reached their highest level at 3 days post injury, whereas T2* values increased and peaked at 24 h in the subcortical region. The change in T2* values was concordant with brain edema. Phase values in the subcortical border region were not dependent on time post-injury. Magnitude values were significantly different from the control group, and increased gradually over time in the subcortical border region. Susceptibility-weighted images (SWI) indicated small petechial hemorrhages in the striatum and thalamus, as well as dilated intramedullary veins. Conclusion: SWI images can be used to detect white and gray matter microhemorrhages and dilated intramedullary veins. The T2*, phase, and magnitude map can also reflect the development of brain injury. Our data illustrate that ESWAN imaging can increase the diagnostic sensitivity and specificity of MRI in neonatal hypoxic-ischemic encephalopathy

  5. 水通道蛋白4抗体对中枢神经炎性脱髓鞘疾病诊断及复发的预测价值%Prognostic value of aquaporin-4 antibody in patients of inflammatory demyelinating diseases in central nervous system

    Institute of Scientific and Technical Information of China (English)

    杨扬; 吴卫平; 黄德晖; 武雷

    2012-01-01

    Objective To determine the prognostic value of AQP4 antibody in the cohort of Chinese patients with neuromyelitis optica ( NMO),HR-NMO( high-risk NMO) and classic multiple sclerosis (MS).Methods Sera of patients with NMO,HR-NMO and MS were all investigated for the presence of AQP4 antibody by indirect immunofluorescence in human AQP4-transfected cells.The diagnostic and prognostic values of anti-AQP4 antibody were evaluated in 352 patients with NMO ( n =106),HR-NMO ( n =84 )including optico-spinal MS (OSMS),longitudinally extensive transverse myelitis (LETM),recurrent optic neuritis (RON) and optic neuritis (ON) or transverse myelitis (TM) with other antoimmune disease and classic MS (n =162).All patients were followed up at outpatient clinics or by telephone.Results In our study,the anti-AQP4 antibody's seropositivity in all demyelinating cases (n =352) was 31.3%.And 72 (65.5%) seropositive patients presented with severe ON,82(74.5% ) with TM,60(54.4% ) with spinalcord lesion more than 3 segments,16( 14.5% ) had relapses of ON and 38(34.5% ) relapses of TM during a follow-up period of 24 months.Significant differences existed between anti-AQP4 antibody seropositivity and seronegative in terms of concurrent severe ON,TM,spinal-cord lesion more than 3 segments and relapses of ON and TM (P < 0.05 ).Also,in NMO patient seropositive for anti-AQP4 antibody ( n =78),28 (35.9%)developed relapses of TM.However,in HR-NMO patient with seropositivity (n =28 ),4 (14.3%)developed relapses of ON and 10(35.7% ) relapses of TM.The relapse of ON or TM occurred in 57/110 seropositive patients versus 17/242 seronegative ones ( P < 0.05 ).Conclusion As compared with antiAQP4 antibody-negative ones,anti-AQP4 antibody-positive patients show significantly higher frequencies of severe ON,TM,longitudinal spinal-cord segments and they are more predisposed to ON or TM relapse.And seropositive NMO and HR-NMO patients are more likely to develop relapses of ON or TM.Anti-AQP

  6. Expression of aquaporin-1 in SMMC-7221 liver carcinoma cells promotes cell migration

    Institute of Scientific and Technical Information of China (English)

    LI Yongming; FENG Xuechao; YANG Hong; MA Tonghui

    2006-01-01

    Migration of tumor cells is a crucial step in tumor invasion and metastasis. Here we provide evidence that aquaporin expression is involved in tumor cell migration. RT-PCR, immunofluorescence and Western blot analysis demonstrated the AQP1 protein expression on the plasma membrane of SMMC-7221 human hepatoma cells. SMMC-7221 cell clones with high (SMMC-7221hPf) and low (SMMC-7221/Pf) water permeability were identified by functional assays with corresponding high and low AQP1 expression. Cell migration rate was remarkably higher in SMMC-7221hPf cells than SMMC-7221/Pf cells, assessed by Boyden chamber and wound healing assays, whereas cell growth and adhesion were not different. Adenovirus-mediated AQP1 expression in SMMC-7221/Pf cells increased their water permeability and migration rate. These results provide the first evidence that aquaporin-mediated membrane water permeability enhances tumor cell migration and may be associated with tumor invasion and metastasis.

  7. One-step extraction of functional recombinant aquaporin Z from inclusion bodies with optimal detergent.

    Science.gov (United States)

    Wang, Lili; Zhou, Hu; Li, Zhengjun; Lim, Teck Kwang; Lim, Xin Shan; Lin, Qingsong

    2015-11-01

    Aquaporins are integral membrane channel proteins found in all kingdoms of life. The Escherichia coli aquaporin Z (AqpZ) has been shown to solely conduct water at high permeability. Functional AqpZ is generally purified from the membrane fraction. However, the quantity of the purified protein is limited. In this study, a new method is developed to achieve high yield of bioactive AqpZ protein. A mild detergent n-dodecyl-β-D-maltopyranoside (DDM) was used to solubilize the over-expressed insoluble AqpZ from inclusion bodies without a refolding process. The recovered AqpZ protein showed high water permeability comparable with AqpZ obtained from the membrane fraction. In this way, the total yield of bioactive AqpZ has been increased greatly, which will facilitate the structural and functional characterization and future applications of AqpZ. PMID:26278820

  8. Effects of Proteoliposome Composition and Draw Solution Types on Separation Performance of Aquaporin-Based Proteoliposomes

    DEFF Research Database (Denmark)

    Zhao, Yang; Vararattanavech, Ardcharaporn; Li, Xuesong;

    2013-01-01

    Aquaporins are a large family of water transport proteins in cell membranes. Their high water permeability and solute rejection make them potential building blocks for high-performance biomimetic membranes for desalination. In the current study, proteoliposomes were prepared using AquaporinZ from...... Escherichia coli cells, and their separation properties were characterized by stopped-flow measurements. The current study systematically investigated the effect of proteoliposome composition (lipid type, protein-to-lipid ratio (PLR), and the addition of cholesterol) on water permeability and NaCl retention....... Among the various lipids investigated, 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC)-based proteoliposomes were found to have excellent osmotic water permeability and NaCl reflection coefficient values. Increasing the PLR of DOPC proteoliposomes up to 1:200 increased their osmotic water permeability...

  9. A Minireview on Vasopressin-regulated Aquaporin-2 in Kidney Collecting Duct Cells.

    Science.gov (United States)

    Park, Eui-Jung; Kwon, Tae-Hwan

    2015-06-01

    The kidney collecting duct is an important renal tubular segment for the regulation of body water and salt homeostasis. Water reabsorption in the collecting duct cells is regulated by arginine vasopressin (AVP) via the vasopressin V2-receptor (V2R). AVP increases the osmotic water permeability of the collecting duct cells through aquaporin-2 (AQP2) and aquaporin-3 (AQP3). AVP induces the apical targeting of AQP2 and transcription of AQP2 gene in the kidney collecting duct principal cells. The signaling transduction pathways resulting in the AQP2 trafficking to the apical plasma membrane of the collecting duct principal cells, include AQP2 phosphorylation, RhoA phosphorylation, actin depolymerization and calcium mobilization, and the changes of AQP2 protein abundance in water balance disorders have been extensively studied. These studies elucidate the underlying cellular and molecular mechanisms of body water homeostasis and provide the basis for the treatment of body water balance disorders. PMID:26240594

  10. The water channel aquaporin-1 contributes to renin cell recruitment during chronic stimulation of renin production

    DEFF Research Database (Denmark)

    Tinning, Anne Robdrup; Jensen, Boye L; Schweda, Frank; Machura, Katharina; Hansen, Pernille B L; Stubbe, Jane; Gramsbergen, Jan Bert; Madsen, Kirsten

    2014-01-01

    Processing and release of secretory granules involve water movement across granule membranes. It was hypothesized that the water channel aquaporin-1 (AQP-1) contributes directly to recruitment of renin-positive cells in the afferent arteriole. AQP1(-/-) and (+/+) mice were fed a low NaCl diet (LS......, 0.004% w/w) for 7 days and given enalapril (ACEI, 0.1 mg/ml) in the drinking water for 3 days. There were no differences in plasma renin concentration at baseline. After LS-ACEI, plasma renin concentration increased markedly in both genotypes but was significantly lower in AQP1(-/-) compared to...... baseline with no difference between genotypes. Plasma nitrite/nitrate concentration was unaffected by genotype and LS-ACEI. In AQP1(-/-) mice, the number of afferent arterioles with recruitment was significantly lower compared to (+/+) after LS-ACEI. It is concluded that aquaporin-1 is not necessary for...

  11. Seed imbibition and germination of Plathymenia reticulata Benth. (Fabaceae) affected by mercury: possible role of aquaporins

    OpenAIRE

    Amanda Ávila Cardoso; Eduardo Euclydes de Lima e Borges; Genaina Aparecida de Souza; Cristiane Jovelina da Silva; Raquel Maria de Oliveira Pires; Denise Cunha Fernandes dos Santos Dias

    2015-01-01

    ABSTRACTStudies that evaluate the physiological and biochemical mechanisms of germination within forest species are needed in order to improve our understanding of such processes. Mercury and dithiothreitol are indicated as important tools in studies that assess the activity of aquaporins during imbibition and germination of seeds. To investigate the alterations caused by mercury inPlathymenia reticulata seedsdifferent doses of mercury were used in the presence and absence of dithiothreitol. ...

  12. The Role of Aquaporins in pH-Dependent Germination of Rhizopus delemar Spores.

    Directory of Open Access Journals (Sweden)

    Tidhar Turgeman

    Full Text Available Rhizopus delemar and associated species attack a wide range of fruit and vegetables after harvest. Host nutrients and acidic pH are required for optimal germination of R. delemar, and we studied how this process is triggered. Glucose induced spore swelling in an acidic environment, expressed by an up to 3-fold increase in spore diameter, whereas spore diameter was smaller in a neutral environment. When suspended in an acidic environment, the spores started to float, indicating a change in their density. Treatment of the spores with HgCl2, an aquaporin blocker, prevented floating and inhibited spore swelling and germ-tube emergence, indicating the importance of water uptake at the early stages of germination. Two putative candidate aquaporin-encoding genes-RdAQP1 and RdAQP2-were identified in the R. delemar genome. Both presented the conserved NPA motif and six-transmembrane domain topology. Expressing RdAQP1 and RdAQP2 in Arabidopsis protoplasts increased the cells' osmotic water permeability coefficient (Pf compared to controls, indicating their role as water channels. A decrease in R. delemar aquaporin activity with increasing external pH suggested pH regulation of these proteins. Substitution of two histidine (His residues, positioned on two loops facing the outer side of the cell, with alanine eliminated the pH sensing resulting in similar Pf values under acidic and basic conditions. Since hydration is critical for spore switching from the resting to activate state, we suggest that pH regulation of the aquaporins can regulate the initial phase of R. delemar spore germination, followed by germ-tube elongation and host-tissue infection.

  13. Upregulation of aquaporin expression in the salivary glands of heat-acclimated rats

    OpenAIRE

    Naotoshi Sugimoto; Kentaro Matsuzaki; Hiroaki Ishibashi; Masao Tanaka; Toshioki Sawaki; Yoshimasa Fujita; Takafumi Kawanami; Yasufumi Masaki; Toshiro Okazaki; Joji Sekine; Shoichi Koizumi; Akihiro Yachie; Hisanori Umehara; Osamu Shido

    2013-01-01

    It is known that aquaporin (AQP) 5 expression in the apical membrane of acinar cells in salivary glands is important for the secretion of saliva in rodents and humans. Although heat acclimation enhances saliva secretion in rodents, the molecular mechanism of how heat induces saliva secretion has not been determined. Here, we found that heat acclimation enhanced the expression of AQP5 and AQP1 in rat submandibular glands concomitant with the promotion of the HIF-1α pathway, leading to VEGF ind...

  14. An upscaling model describing root radial hydraulic conductivity from cross section anatomy and aquaporin expression patterns

    OpenAIRE

    Couvreur, Valentin; Faget, Marc; Javaux, Mathieu; Chaumont, Francois; Draye, Xavier; 2016 Kirkham Conference

    2016-01-01

    Objectives: To improve our understanding of aquaporin (AQP) expression patterns and root anatomy effects on radial hydraulic conductivity by combining quantitative in vivo and in silico experiments from the cell to the root cross-section scales in various hydric environments. Methods: A program generates explicit 2D root cross-section hydraulic networks from cross-section anatomy images. The hydraulic network includes "cell wall" and "intra cell" nodes constituting connected pathways allowing...

  15. Cellular Localization of Aquaporin-1 in the Human and Mouse Trigeminal Systems

    OpenAIRE

    Gao, Junying; Tan, Meiyun; Gu, Minxia; Marshall, Charles; Ding, Jiong; Hu, Gang; Xiao, Ming

    2012-01-01

    Previous studies reported that a subpopulation of mouse and rat trigeminal neurons express water channel aquaporin-1 (AQP1). In this study we make a comparative investigation of AQP1 localization in the human and mouse trigeminal systems. Immunohistochemistry and immunofluorescence results showed that AQP1 was localized to the cytoplasm and cell membrane of some medium and small-sized trigeminal neurons. Additionally, AQP1 was found in numerous peripheral trigeminal axons of humans and mice. ...

  16. Comparative functional analysis of aquaporins/glyceroporins in mammals and anurans

    OpenAIRE

    Krane, Carissa M.; Goldstein, David L.

    2007-01-01

    Maintenance of fluid homeostasis is critical to establishing and maintaining normal physiology. The landmark discovery of membrane water channels (aquaporins; AQPs) ushered in a new area in osmoregulatory biology that has drawn from and contributed to diverse branches of biology, from molecular biology and genomics to systems biology and evolution, and from microbial and plant biology to animal and translational physiology. As a result, the study of AQPs provides a unique and integrated backd...

  17. Decreased Aquaporin Expression Leads to Increased Resistance to Apoptosis in Hepatocellular Carcinoma

    OpenAIRE

    Jablonski, Elizabeth M.; Mattocks, M. Adrian; Sokolov, Eugene; Koniaris, Leonidas G.; Hughes, Francis M; Fausto, Nelson; Pierce, Robert H.; Mckillop, Iain H.

    2006-01-01

    Cells undergoing apoptosis are characterized by decreased cell size due to changes in intracellular ion concentration and rapid, aquaporin (AQP)-dependent water movement out of the cell, events required for the activation of pro-apoptotic enzymes. The current study demonstrates AQP 8 and 9 expression is significantly decreased in hepatocellular carcinoma (HCC) versus normal liver. Isolation of hepatic tumor cells (H4IIE) and hepatocytes confirmed a lack of water movement across the H4IIE cell...

  18. Aquaporin-2: new mutations responsible for autosomal-recessive nephrogenic diabetes insipidus—update and epidemiology

    OpenAIRE

    Bichet, Daniel G.; El Tarazi, Abdulah; Matar, Jessica; Lussier, Yoann; Arthus, Marie-Françoise; Lonergan, Michèle; Bockenhauer, Detlef; Bissonnette, Pierre

    2012-01-01

    It is clinically useful to distinguish between two types of hereditary nephrogenic diabetes insipidus (NDI): a ‘pure’ type characterized by loss of water only and a complex type characterized by loss of water and ions. Patients with congenital NDI bearing mutations in the vasopressin 2 receptor gene, AVPR2, or in the aquaporin-2 gene, AQP2, have a pure NDI phenotype with loss of water but normal conservation of sodium, potassium, chloride and calcium. Patients with hereditary hypokalemic salt...

  19. Identification and characterization of plasma membrane aquaporins isolated from fiber cells of Calotropis procera

    OpenAIRE

    Aslam, Usman; Khatoon, Asia; Cheema, Hafiza Masooma Naseer; Bashir, Aftab

    2013-01-01

    Calotropis procera, commonly known as “milkweed”, possesses long seed trichomes for seed dispersal and has the ability to survive under harsh conditions such as drought and salinity. Aquaporins are water channel proteins expressed in all land plants, divided into five subfamilies plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), NOD26-like proteins (NIPs), small basic intrinsic proteins (SIPs), and the unfamiliar X intrinsic proteins (XIPs). PIPs constitute the l...

  20. Root ABA Accumulation Enhances Rice Seedling Drought Tolerance under Ammonium Supply: Interaction with Aquaporins.

    Science.gov (United States)

    Ding, Lei; Li, Yingrui; Wang, Ying; Gao, Limin; Wang, Min; Chaumont, François; Shen, Qirong; Guo, Shiwei

    2016-01-01

    In previous studies, we demonstrated that ammonium nutrition enhances the drought tolerance of rice seedlings compared to nitrate nutrition and contributes to a higher root water uptake ability. It remains unclear why rice seedlings maintain a higher water uptake ability when supplied with ammonium under drought stress. Here, we focused on the effects of nitrogen form and drought stress on root abscisic acid (ABA) concentration and aquaporin expression using hydroponics experiments and stimulating drought stress with 10% PEG6000. Drought stress decreased the leaf photosynthetic rate and stomatal conductivity and increased the leaf temperature of plants supplied with either ammonium or nitrate, but especially under nitrate supply. After 4 h of PEG treatment, the root protoplast water permeability and the expression of root PIP and TIP genes decreased in plants supplied with ammonium or nitrate. After 24 h of PEG treatment, the root hydraulic conductivity, the protoplast water permeability, and the expression of some aquaporin genes increased in plants supplied with ammonium compared to those under non-PEG treatment. Root ABA accumulation was induced by 24 h of PEG treatment, especially in plants supplied with ammonium. The addition of exogenous ABA decreased the expression of PIP and TIP genes under non-PEG treatment but increased the expression of some of them under PEG treatment. We concluded that drought stress induced a down-regulation of aquaporin expression, which appeared earlier than did root ABA accumulation. With continued drought stress, aquaporin expression and activity increased due to root ABA accumulation in plants supplied with ammonium. PMID:27559341

  1. The Role of Aquaporins in pH-Dependent Germination of Rhizopus delemar Spores.

    Science.gov (United States)

    Turgeman, Tidhar; Shatil-Cohen, Arava; Moshelion, Menachem; Teper-Bamnolker, Paula; Skory, Christopher D; Lichter, Amnon; Eshel, Dani

    2016-01-01

    Rhizopus delemar and associated species attack a wide range of fruit and vegetables after harvest. Host nutrients and acidic pH are required for optimal germination of R. delemar, and we studied how this process is triggered. Glucose induced spore swelling in an acidic environment, expressed by an up to 3-fold increase in spore diameter, whereas spore diameter was smaller in a neutral environment. When suspended in an acidic environment, the spores started to float, indicating a change in their density. Treatment of the spores with HgCl2, an aquaporin blocker, prevented floating and inhibited spore swelling and germ-tube emergence, indicating the importance of water uptake at the early stages of germination. Two putative candidate aquaporin-encoding genes-RdAQP1 and RdAQP2-were identified in the R. delemar genome. Both presented the conserved NPA motif and six-transmembrane domain topology. Expressing RdAQP1 and RdAQP2 in Arabidopsis protoplasts increased the cells' osmotic water permeability coefficient (Pf) compared to controls, indicating their role as water channels. A decrease in R. delemar aquaporin activity with increasing external pH suggested pH regulation of these proteins. Substitution of two histidine (His) residues, positioned on two loops facing the outer side of the cell, with alanine eliminated the pH sensing resulting in similar Pf values under acidic and basic conditions. Since hydration is critical for spore switching from the resting to activate state, we suggest that pH regulation of the aquaporins can regulate the initial phase of R. delemar spore germination, followed by germ-tube elongation and host-tissue infection. PMID:26959825

  2. Seed imbibition and germination of Plathymenia reticulata Benth. (Fabaceae affected by mercury: possible role of aquaporins

    Directory of Open Access Journals (Sweden)

    Amanda Ávila Cardoso

    2015-09-01

    Full Text Available ABSTRACTStudies that evaluate the physiological and biochemical mechanisms of germination within forest species are needed in order to improve our understanding of such processes. Mercury and dithiothreitol are indicated as important tools in studies that assess the activity of aquaporins during imbibition and germination of seeds. To investigate the alterations caused by mercury inPlathymenia reticulata seedsdifferent doses of mercury were used in the presence and absence of dithiothreitol. Mercury had a dose-dependent effect on the seeds; in the most dilute solutions mercury partially inhibited the imbibition process, whereas in the most concentrated solutions it caused the death of the embryos. A delay in the hydration of the seeds may have caused decreased germination as a result of the reduced functionality of the aquaporins that were oxidized by mercury. In the presence of the reducing agent dithiothreitol, the activity of these proteins was restored and the germination process was re-established. These findings indicate the importance of aquaporins in the imbibition and germination stages of P. reticulataseeds, and they provide a better understanding of these important developmental events in plants.

  3. Effects of Repeated Administration of Pilocarpine and Isoproterenol on Aquaporin-5 Expression in Rat Salivary Glands

    International Nuclear Information System (INIS)

    Aquaporins are water channel proteins which enable rapid water movement across the plasma membrane. Aquaporin-5 (AQP5) is the major aquaporin and is expressed on the apical membrane of salivary gland acinar cells. We examined the effects of repeated administration of pilocarpine, a clinically useful stimulant for salivary fluid secretion, and isoproterenol (IPR), a stimulant for salivary protein secretion, on the abundance of AQP5 protein in rat salivary glands by immunofluorescence microscopy and semi-quantitative immunoblotting. Unexpectedly AQP5 was decreased in pilocarpine-administered salivary glands, in which fluid secretion must be highly stimulated, implying that AQP5 might not be required for fluid secretion at least in pilocarpine-administered state. The abundance of AQP5, on the other hand, was found to be significantly increased in IPR-administered submandibular and parotid glands. To address the possible mechanism of the elevation of AQP5 abundance in IPR-administered animals, changes of AQP5 level in fasting animals, in which the exocytotic events are reduced, were examined. AQP5 was found to be decreased in fasting animals as expected. These results suggested that the elevation of cAMP and/or frequent exocytotic events could increase AQP5 protein. AQP5 expression seems to be easily changed by salivary stimulants, although these changes do not always reflect the ability in salivary fluid secretion

  4. The gating mechanism of the human aquaporin 5 revealed by molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Lorant Janosi

    Full Text Available Aquaporins are protein channels located across the cell membrane with the role of conducting water or other small sugar alcohol molecules (aquaglyceroporins. The high-resolution X-ray structure of the human aquaporin 5 (HsAQP5 shows that HsAQP5, as all the other known aquaporins, exhibits tetrameric structure. By means of molecular dynamics simulations we analyzed the role of spontaneous fluctuations on the structural behavior of the human AQP5. We found that different conformations within the tetramer lead to a distribution of monomeric channel structures, which can be characterized as open or closed. The switch between the two states of a channel is a tap-like mechanism at the cytoplasmic end which regulates the water passage through the pore. The channel is closed by a translation of the His67 residue inside the pore. Moreover, water permeation rate calculations revealed that the selectivity filter, located at the other end of the channel, regulates the flow rate of water molecules when the channel is open, by locally modifying the orientation of His173. Furthermore, the calculated permeation rates of a fully open channel are in good agreement with the reported experimental value.

  5. Role of Aquaporin-4 in Cerebral Edema and Stroke

    OpenAIRE

    Zador, Zsolt; Stiver, Shirley; Wang, Vincent; Manley, Geoffrey T.

    2009-01-01

    Cerebral edema plays a central role in the pathophysiology of many diseases of the central nervous system (CNS) including ischemia, trauma, tumors, inflammation, and metabolic disturbances. The formation of cerebral edema results in an increase in tissue water content and brain swelling which, if unchecked, can lead to elevated intracranial pressure (ICP), reduced cerebral blood flow, and ultimately cerebral herniation and death. Despite the clinical significance of cerebral edema, the mechan...

  6. Recombinant Production of Human Aquaporin-1 to an Exceptional High Membrane Density in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Bomholt, Julie; Helix Nielsen, Claus; Scharff-Poulsen, Peter; Pedersen, Per Amstrup

    2013-01-01

    -folding. Reduction of the expression temperature to 15°C almost completely prevented Aquaporin-1 mal-folding. Bioimaging of live yeast cells revealed that recombinant Aquaporin-1 accumulated in the yeast plasma membrane. A detergent screen for solubilization revealed that CYMAL-5 was superior in solubilizing...

  7. Neuromyelitis optica study model based on chronic infusion of autoantibodies in rat cerebrospinal fluid

    OpenAIRE

    Marignier, R.; Ruiz, A.; Cavagna, S.; Nicole, A; Watrin, C.; Touret, M.; Parrot, S; Malleret, G.; Peyron, C.; Benetollo, C.; Auvergnon, N.; Vukusic, S.; Giraudon, P.

    2016-01-01

    Background Devic’s neuromyelitis optica (NMO) is an autoimmune astrocytopathy, associated with central nervous system inflammation, demyelination, and neuronal injury. Several studies confirmed that autoantibodies directed against aquaporin-4 (AQP4-IgG) are relevant in the pathogenesis of NMO, mainly through complement-dependent toxicity leading to astrocyte death. However, the effect of the autoantibody per se and the exact role of intrathecal AQP4-IgG are still controversial. Methods To exp...

  8. Vasopressin receptors V1a and V2 are not osmosensors

    DEFF Research Database (Denmark)

    Lykke, Kasper; Assentoft, Mette; Fenton, Robert A;

    2015-01-01

    in AQP4-dependent water permeability was observed, although osmotic challenges failed to mimic vasopressin-dependent V1aR-mediated internalization of AQP4. Direct monitoring of inositol phosphate (IP) production of V1aR-expressing COS-7 cells demonstrated an efficient vasopressin-dependent response....... The V1aR-dependent response was monitored indirectly via its effects on aquaporin 4 (AQP4) when heterologously expressed in Xenopus oocytes and V1aR and V2R function was directly monitored following heterologous expression in COS-7 cells. A tendency toward an osmotically induced, V1aR-mediated reduction...

  9. Brain Basics

    Medline Plus

    Full Text Available ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  10. Brain Basics

    Science.gov (United States)

    ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  11. Brain Basics

    Medline Plus

    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... learning more about how the brain grows and works in healthy people, and how normal brain development ...

  12. Zinc modulation of water permeability reveals that aquaporin 0 functions as a cooperative tetramer.

    Science.gov (United States)

    Németh-Cahalan, Karin L; Kalman, Katalin; Froger, Alexandrine; Hall, James E

    2007-11-01

    We previously showed that the water permeability of AQP0, the water channel of the lens, increases with acid pH and that His40 is required (Németh-Cahalan, K.L., and J.E. Hall. 2000. J. Biol. Chem. 275:6777-6782; Németh-Cahalan, K.L., K. Kalman, and J.E. Hall. 2004. J. Gen. Physiol. 123:573-580). We have now investigated the effect of zinc (and other transition metals) on the water permeability of AQP0 expressed in Xenopus oocytes and determined the amino acid residues that facilitate zinc modulation. Zinc (1 mM) increased AQP0 water permeability by a factor of two and prevented any additional increase induced by acid pH. Zinc had no effect on water permeability of AQP1, AQP4 or MIPfun (AQP0 from killifish), or on mutants of AQP1 and MIPfun with added external histidines. Nickel, but not copper, had the same effect on AQP0 water permeability as zinc. A fit of the concentration dependence of the zinc effect to the Hill equation gives a coefficient greater than three, suggesting that binding of more than one zinc ion is necessary to enhance water permeability. His40 and His122 are necessary for zinc modulation of AQP0 water permeability, implying structural constraints for zinc binding and functional modulation. The change in water permeability was highly sensitive to a coinjected zinc-insensitive mutant and a single insensitive monomer completely abolished zinc modulation. Our results suggest a model in which positive cooperativity among subunits of the AQP0 tetramer is required for zinc modulation, implying that the tetramer is the functional unit. The results also offer the possibility of a pharmacological approach to manipulate the water permeability and transparency of the lens. PMID:17938229

  13. Serum peptide reactivities may distinguish neuromyelitis optica subgroups and multiple sclerosis

    Science.gov (United States)

    Metz, Imke; Beißbarth, Tim; Ellenberger, David; Pache, Florence; Stork, Lidia; Ringelstein, Marius; Aktas, Orhan; Jarius, Sven; Wildemann, Brigitte; Dihazi, Hassan; Friede, Tim; Ruprecht, Klemens; Paul, Friedemann

    2016-01-01

    Objective: To assess in an observational study whether serum peptide antibody reactivities may distinguish aquaporin-4 (AQP4) antibody (Ab)–positive and -negative neuromyelitis optica spectrum disorders (NMOSD) and relapsing-remitting multiple sclerosis (RRMS). Methods: We screened 8,700 peptides that included human and viral antigens of potential relevance for inflammatory demyelinating diseases and random peptides with pooled sera from different patient groups and healthy controls to set up a customized microarray with 700 peptides. With this microarray, we tested sera from 66 patients with AQP4-Ab-positive (n = 16) and AQP4-Ab-negative (n = 19) NMOSD, RRMS (n = 11), and healthy controls (n = 20). Results: Differential peptide reactivities distinguished NMOSD subgroups from RRMS in 80% of patients. However, the 2 NMOSD subgroups were not well-discriminated, although those patients are clearly separated by their antibody reactivities against AQP4 in cell-based assays. Elevated reactivities to myelin and Epstein-Barr virus peptides were present in RRMS and to AQP4 and AQP1 peptides in AQP4-Ab-positive NMOSD. Conclusions: While AQP4-Ab-positive and -negative NMOSD subgroups are not well-discriminated by peptide antibody reactivities, our findings suggest that peptide antibody reactivities may have the potential to distinguish between both NMOSD subgroups and MS. Future studies should thus concentrate on evaluating peptide antibody reactivities for the differentiation of AQP4-Ab-negative NMOSD and MS. PMID:26894206

  14. Aquaporin JcPIP2 is Involved in Drought Responses in Jatropha curcas

    Institute of Scientific and Technical Information of China (English)

    Ying ZHANG; Yunxiao WANG; Luding JIANG; Ying XU; Yingchun WANG; Daihua LU; Fang CHEN

    2007-01-01

    Water channel proteins, aquaporins, play fundamental roles in transmembrane water movements in plants. A new full-length cDNA encoding aquaporin was isolated from the seedlings of Jatropha curcas.The gene of the plasma membrane intrinsic protein (PIP) from J. curcas (JcPIP2) contained an 843 bp open reading frame encoding a protein of 280 amino acids. The amino acid sequence showed 94% identity with Ricinus communis PIP. Injection of JcPIP2 complementary RNA into Xenopus oocytes increased 10-fold the osmotic water permeability of the oocytes. Immunodetection of JcPIP2 with anti-JcPIP2 antibody indicated that this protein is ubiquitously located in all tested tissues of the plant. To investigate the relationship between aquaporins and drought resistance in J. curcas, the abundance of JcPIP2 was examined in seedlings of two J. curcas populations, Gao You CSC63 and YanBian S1, under water deficit with PEG6000. Under field conditions, those two populations, Gao You CSC63 was resistant to water deficit, but YanBian S1 was sensitive to water deprivation. With the increasing degree of drought stress, JcPIP2 level increased in seedlings of Gao You CSC63, whereas there was no significant change in seedlings of YanBian S1. Compared with YanBian S1, GaoYou CSC63 also showed higher root hydraulic conductivity and lower decreasing trend in the seedlings under water deficit. These results indicated that JcPIP2 probably played a role in drought resistance in J. curcas.

  15. Aquaporin expression and cell volume regulation in the SV40 immortalized rat submandibular acinar cell line.

    Science.gov (United States)

    Hansen, Ann-Kristin; Galtung, Hilde Kanli

    2007-03-01

    The amount of aquaporins present and the cellular ability to perform regulatory volume changes are likely to be important for fluid secretions from exocrine glands. In this work these phenomena were studied in an SV40 immortalized rat submandibular acinar cell line. The regulatory cell volume characteristics have not previously been determined in these cells. Cell volume regulation following hyposmotic exposure and aquaporin induction was examined with Coulter counter methodology, radioactive efflux studies, fura-2 fluorescence, and polymerase chain reaction and Western blot techniques. Cell volume regulation was inhibited by the K(+) channel antagonists quinine and BaCl(2) and the Cl(-) channel blocker 5-nitro-2-(3-phenypropylamino)benzoic acid. A concomitant increase in cellular (3)H-taurine release and Ca(2+) concentration was also observed. Chelation of both intra- and extracellular Ca(2+) with EGTA and the Ca(2+) ionophore A23187 did not, however, affect cell volume regulation. Aquaporin 5 (AQP5) mRNA and protein levels were upregulated in hyperosmotic conditions and downregulated upon return to isosmotic solutions, but were reduced by the mitogen-activated ERK-activating kinase (MEK) inhibitor U0126. A 24-h MEK inhibition also diminished hyposmotically induced cell swelling and cell volume regulation. In conclusion, it was determined that regulatory volume changes in this immortalized cell line are due to KCl and taurine efflux. In conditions that increased AQP5 levels, the cells showed a faster cell swelling and a more complete volume recovery following hyposmotic exposure. This response could be overturned by MEK inhibition. PMID:17021794

  16. Loop A is critical for the functional interaction of two Beta vulgaris PIP aquaporins.

    Science.gov (United States)

    Jozefkowicz, Cintia; Rosi, Pablo; Sigaut, Lorena; Soto, Gabriela; Pietrasanta, Lía Isabel; Amodeo, Gabriela; Alleva, Karina

    2013-01-01

    Research done in the last years strongly support the hypothesis that PIP aquaporin can form heterooligomeric assemblies, specially combining PIP2 monomers with PIP1 monomers. Nevertheless, the structural elements involved in the ruling of homo versus heterooligomeric organization are not completely elucidated. In this work we unveil some features of monomer-monomer interaction in Beta vulgaris PIP aquaporins. Our results show that while BvPIP2;2 is able to interact with BvPIP1;1, BvPIP2;1 shows no functional interaction. The lack of functional interaction between BvPIP2;1 and BvPIP1;1 was further corroborated by dose-response curves of water permeability due to aquaporin activity exposed to different acidic conditions. We also found that BvPIP2;1 is unable to translocate BvPIP1;1-ECFP from an intracellular position to the plasma membrane when co-expressed, as BvPIP2;2 does. Moreover we postulate that the first extracellular loop (loop A) of BvPIP2;1, could be relevant for the functional interaction with BvPIP1;1. Thus, we investigate BvPIP2;1 loop A at an atomic level by Molecular Dynamics Simulation (MDS) and by direct mutagenesis. We found that, within the tetramer, each loop A presents a dissimilar behavior. Besides, BvPIP2;1 loop A mutants restore functional interaction with BvPIP1;1. This work is a contribution to unravel how PIP2 and PIP1 interact to form functional heterooligomeric assemblies. We postulate that BvPIP2;1 loop A is relevant for the lack of functional interaction with BvPIP1;1 and that the monomer composition of PIP assemblies determines their functional properties. PMID:23483963

  17. Loop A is critical for the functional interaction of two Beta vulgaris PIP aquaporins.

    Directory of Open Access Journals (Sweden)

    Cintia Jozefkowicz

    Full Text Available Research done in the last years strongly support the hypothesis that PIP aquaporin can form heterooligomeric assemblies, specially combining PIP2 monomers with PIP1 monomers. Nevertheless, the structural elements involved in the ruling of homo versus heterooligomeric organization are not completely elucidated. In this work we unveil some features of monomer-monomer interaction in Beta vulgaris PIP aquaporins. Our results show that while BvPIP2;2 is able to interact with BvPIP1;1, BvPIP2;1 shows no functional interaction. The lack of functional interaction between BvPIP2;1 and BvPIP1;1 was further corroborated by dose-response curves of water permeability due to aquaporin activity exposed to different acidic conditions. We also found that BvPIP2;1 is unable to translocate BvPIP1;1-ECFP from an intracellular position to the plasma membrane when co-expressed, as BvPIP2;2 does. Moreover we postulate that the first extracellular loop (loop A of BvPIP2;1, could be relevant for the functional interaction with BvPIP1;1. Thus, we investigate BvPIP2;1 loop A at an atomic level by Molecular Dynamics Simulation (MDS and by direct mutagenesis. We found that, within the tetramer, each loop A presents a dissimilar behavior. Besides, BvPIP2;1 loop A mutants restore functional interaction with BvPIP1;1. This work is a contribution to unravel how PIP2 and PIP1 interact to form functional heterooligomeric assemblies. We postulate that BvPIP2;1 loop A is relevant for the lack of functional interaction with BvPIP1;1 and that the monomer composition of PIP assemblies determines their functional properties.

  18. Brain herniation

    Science.gov (United States)

    ... herniation; Uncal herniation; Subfalcine herniation; Tonsillar herniation; Herniation - brain ... Brain herniation occurs when something inside the skull produces pressure that moves brain tissues. This is most ...

  19. Role of renal aquaporins in escape from vasopressin-induced antidiuresis in rat.

    OpenAIRE

    Ecelbarger, C A; S. Nielsen; Olson, B R; Murase, T; Baker, E A; Knepper, M A; Verbalis, J G

    1997-01-01

    The purpose of this study was to investigate whether escape from vasopressin-induced antidiuresis is associated with altered regulation of any of the known aquaporin water channels. After 4-d pretreatment with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) by osmotic mini-pump, rats were divided into two groups: control (continued dDAVP) and water-loaded (continued dDAVP plus a daily oral water load). A significant increase in urine volume in the water-loaded rats was observed by the second day...

  20. Overexpression of the Wheat Aquaporin Gene, TaAQP7, Enhances Drought Tolerance in Transgenic Tobacco

    OpenAIRE

    Shiyi Zhou; Wei Hu; Xiaomin Deng; Zhanbing Ma; Lihong Chen; Chao Huang; Chen Wang,; Jie Wang; Yanzhen He; Guangxiao Yang; Guangyuan He

    2012-01-01

    Aquaporin (AQP) proteins have been shown to transport water and other small molecules through biological membranes, which is crucial for plants to combat stress caused by drought. However, the precise role of AQPs in drought stress response is not completely understood in plants. In this study, a PIP2 subgroup gene AQP, designated as TaAQP7, was cloned and characterized from wheat. Expression of TaAQP7-GFP fusion protein revealed its localization in the plasma membrane. TaAQP7 exhibited high ...

  1. Relationship between Hexokinase and the Aquaporin PIP1 in the Regulation of Photosynthesis and Plant Growth

    OpenAIRE

    Kelly, Gilor; Sade, Nir; Attia, Ziv; Secchi, Francesca; Zwieniecki, Maciej; Holbrook, N. Michele; Levi, Asher; Alchanatis, Victor; Moshelion, Menachem; Granot, David

    2014-01-01

    Increased expression of the aquaporin NtAQP1, which is known to function as a plasmalemma channel for CO2 and water, increases the rate of both photosynthesis and transpiration. In contrast, increased expression of Arabidopsis hexokinase1 (AtHXK1), a dual-function enzyme that mediates sugar sensing, decreases the expression of photosynthetic genes and the rate of transpiration and inhibits growth. Here, we show that AtHXK1 also decreases root and stem hydraulic conductivity and leaf mesophyll...

  2. Water transport and functional dynamics of aquaporins in osmoregulatory organs of fishes

    DEFF Research Database (Denmark)

    Madsen, Steffen S; Engelund, Morten B; Cutler, Christopher P

    2015-01-01

    salty desert lakes, the challenge to obtain consensus as well as specific knowledge about aquaporin physiology in these vertebrate clades is overwhelming. Because the integumental surfaces of these animals are in intimate contact with the surrounding milieu, passive water loss and uptake represent two...... transport in osmoregulatory organs in euryhaline species - primarily teleosts, but covering other taxonomic groups as well. Most current knowledge comes from teleosts, and there is a strong need for related information on older fish clades. Our survey aims to stimulate new, original research in this area...

  3. Increasing gene dosage greatly enhances recombinant expression of aquaporins in Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Kjellbom Per

    2011-05-01

    Full Text Available Abstract Background When performing functional and structural studies, large quantities of pure protein are desired. Most membrane proteins are however not abundantly expressed in their native tissues, which in general rules out purification from natural sources. Heterologous expression, especially of eukaryotic membrane proteins, has also proven to be challenging. The development of expression systems in insect cells and yeasts has resulted in an increase in successful overexpression of eukaryotic proteins. High yields of membrane protein from such hosts are however not guaranteed and several, to a large extent unexplored, factors may influence recombinant expression levels. In this report we have used four isoforms of aquaporins to systematically investigate parameters that may affect protein yield when overexpressing membrane proteins in the yeast Pichia pastoris. Results By comparing clones carrying a single gene copy, we show a remarkable variation in recombinant protein expression between isoforms and that the poor expression observed for one of the isoforms could only in part be explained by reduced transcript levels. Furthermore, we show that heterologous expression levels of all four aquaporin isoforms strongly respond to an increase in recombinant gene dosage, independent of the amount of protein expressed from a single gene copy. We also demonstrate that the increased expression does not appear to compromise the protein folding and the membrane localisation. Conclusions We report a convenient and robust method based on qPCR to determine recombinant gene dosage. The method is generic for all constructs based on the pPICZ vectors and offers an inexpensive, quick and reliable means of characterising recombinant P. pastoris clones. By using this method we show that: (1 heterologous expression of all aquaporins investigated respond strongly to an increase in recombinant gene dosage (2 expression from a single recombinant gene copy varies

  4. Concerted action of two cation filters in the aquaporin water channel

    DEFF Research Database (Denmark)

    Wu, Binghua; Steinbronn, Christina; Alsterfjord, Magnus;

    2009-01-01

    Aquaporin (AQP) facilitated water transport is common to virtually all cell membranes and is marked by almost perfect specificity and high flux rates. Simultaneously, protons and cations are strictly excluded to maintain ionic transmembrane gradients. Yet, the AQP cation filters have not been...... identified experimentally. We report that three point mutations turned the water-specific AQP1 into a proton/alkali cation channel with reduced water permeability and the permeability sequence: H(+) >>K(+) >Rb(+) >Na(+) >Cs(+) >Li(+). Contrary to theoretical models, we found that electrostatic repulsion...

  5. Downregulation of aquaporin-1 in alveolar microvessels in lungs adapted to chronic heart failure

    DEFF Research Database (Denmark)

    Müllertz, Katrine M; Strøm, Claes; Trautner, Simon;

    2011-01-01

    The threshold pressure for lung edema formation is increased in severe chronic heart failure (CHF) due to reduced microvascular permeability. The water channel aquaporin-1 (AQP1) is present in the pulmonary microvascular endothelium, and a number of studies suggest the importance of AQP1...... as a molecular determinant of pulmonary microvascular water transport. The present study examined the abundance and localization of AQP1 in lungs from rats with CHF. We used two different models of CHF: ligation of the left anterior descending coronary artery (LAD ligation) and aorta-banding (AB). Sham...

  6. Functional challenge affects aquaporin mRNA abundance in mouse blastocysts

    DEFF Research Database (Denmark)

    Offenberg, Hanne Kjær; Thomsen, Preben Dybdahl

    2005-01-01

    The aquaporins (AQPs) are a family of channel proteins that facilitate diffusion of water across cell membranes. Three members of the AQP family have been detected in the mouse blastocyst: AQP 3 and 8 are located in the basolateral domain and AQP 9 predominantly in the apical domain of the tropho...... in vivo developed blastocysts. We found that in vitro culture resulted in lower levels of AQP 8, 9, and 11 compared to in vivo development. These experiments show that mouse embryos are capable of regulating AQP mRNA abundances in response to environmental alterations....

  7. Brain Basics

    Medline Plus

    Full Text Available ... Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain growth in children with autism ...

  8. A novel mutation affecting the arginine-137 residue of AVPR2 in dizygous twins leads to nephrogenic diabetes insipidus and attenuated urine exosome aquaporin-2

    DEFF Research Database (Denmark)

    Hinrichs, Gitte R; Hansen, Louise H; Nielsen, Maria R;

    2016-01-01

    Mutations in the vasopressin V2 receptor gene AVPR2 may cause X-linked nephrogenic diabetes insipidus by defective apical insertion of aquaporin-2 in the renal collecting duct principal cell. Substitution mutations with exchange of arginine at codon 137 can cause nephrogenic syndrome of inappropr...... administration. While a similar urine exosome release rate was shown between probands and controls by western blotting for the marker ALIX, there was a selective decrease in exosome aquaporin-2 versus aquaporin-1 protein in probands compared to controls....

  9. X-ray structure of human aquaporin 2 and its implications for nephrogenic diabetes insipidus and trafficking

    NARCIS (Netherlands)

    Frick, A.; Eriksson, U.K.; Mattia, F.P. de; Oberg, F.; Hedfalk, K.; Neutze, R.; Grip, W.J. de; Deen, P.M.T.; Tornroth-Horsefield, S.

    2014-01-01

    Human aquaporin 2 (AQP2) is a water channel found in the kidney collecting duct, where it plays a key role in concentrating urine. Water reabsorption is regulated by AQP2 trafficking between intracellular storage vesicles and the apical membrane. This process is tightly controlled by the pituitary h

  10. 肺水通道蛋白的研究进展%Research Progress of Aquaporin in Lung

    Institute of Scientific and Technical Information of China (English)

    刘毅(综述); 史振伟(审校)

    2014-01-01

    Adjusting the water permeability of the cell membrane is the basic requirements for life main-tain. Aquaporin is a group of transporters which related to water permeability. Studies show that,aquaporin expression or function changes can rate-limiting the water transport speed. Aquaporin abnormity expressing may be related to variety of clinical forms of edema altering the water balance could treatment the diseases. Aquaporin plays an important role in maintains the balance of lung fluid in the pathogenesis of primary and secondary pulmonary edema.%调节细胞膜的水渗透性是维持生命的基本要求,水通道蛋白是细胞膜上一组与水通透性有关的转运蛋白。目前研究表明,水通道蛋白表达或功能的改变,可以改变细胞膜转运水的速度。水通道蛋白的异常表达可能与临床上各种形式的水肿形成相关,通过改变体内水的平衡可达到治疗疾病的目的。水通道蛋白在维持肺脏的液体平衡中同样起重要的作用。

  11. Does the hourglass shape of aquaporins optimize water permeability This research was supported by the ERC program, project Micromegas.

    Science.gov (United States)

    Gravelle, Simon; Joly, Laurent; Detcheverry, François; Ybert, Christophe; Cottin-Bizonne, Cecile; Bocquet, Lyderic; Liquide et interfaces Team

    2013-11-01

    The ubiquitous aquaporin channels are able to conduct water across cell membranes, combining the seemingly antagonist functions of a very high selectivity with a remarkable permeability. While molecular details are obvious keys to perform these tasks, the overall efficiency of transport in such nanopores is also strongly limited by viscous dissipation arising at the connection between the nanoconstriction and the nearby bulk reservoirs. In this contribution, we focus on these so-called entrance effects and specifically examine whether the characteristic hourglass shape of aquaporins may arise from a geometrical optimum for such hydrodynamic dissipation. Using a combination of finite element calculations and analytical modeling, we show that conical entrances with suitable opening angle can indeed provide a large increase of the overall channel permeability. Moreover, the optimal opening angles that maximize the permeability are found to compare well with the angles measured in a large variety of aquaporins. This suggests that the hourglass shape of aquaporins could be the result of a natural selection process toward optimal hydrodynamic transport. Finally, in a biomimetic perspective, these results provide guidelines to design artificial nanopores with optimal performances.

  12. Structure and Stability of the Spinach Aquaporin SoPIP2;1 in Detergent Micelles and Lipid Membranes

    DEFF Research Database (Denmark)

    Plasencia, Ines; Survery, Sabeen; Ibragimova, Sania;

    2011-01-01

    Background: SoPIP2;1 constitutes one of the major integral proteins in spinach leaf plasma membranes and belongs to the aquaporin family. SoPIP2;1 is a highly permeable and selective water channel that has been successfully overexpressed and purified with high yields. In order to optimize...

  13. Population shift between the open and closed states changes the water permeability of an Aquaporin Z mutant.

    Science.gov (United States)

    Xin, Lin; Hélix-Nielsen, Claus; Su, Haibin; Torres, Jaume; Tang, Chuyang; Wang, Rong; Fane, Anthony Gordon; Mu, Yuguang

    2012-07-18

    Aquaporins are tetrameric transmembrane channels permeable to water and other small solutes. Wild-type (WT) and mutant Aquaporin Z (AqpZ) have been widely studied and multiple factors have been found to affect their water permeability. In this study, molecular dynamics simulations have been performed for the tetrameric AqpZ F43W/H174G/T183F mutant. It displayed ∼10% average water permeability compared to WT AqpZ, which had been attributed to the increased channel lumen hydrophobicity. Our simulations, however, show a ring stacking between W43 and F183 acting as a secondary steric gate in the triple mutant with R189 as the primary steric gate in both mutant and WT AqpZ. The double gates (R189 and W43-F183) result in a high population of the closed conformation in the mutant. Occasionally an open state, with diffusive water permeability very close to that of WT AqpZ, was observed. Taken together, our results show that the double-gate mechanism is sufficient to explain the reduced water permeability in the mutant without invoking effects arising from increased hydrophobicity of the channel lumen. Our findings provide insights into how aquaporin-mediated water transport can be modulated and may further point to how aquaporin function can be optimized for biomimetic membrane applications. PMID:22853898

  14. Toward understanding the selective anticancer capacity of cold atmospheric plasma--a model based on aquaporins (Review).

    Science.gov (United States)

    Yan, Dayun; Talbot, Annie; Nourmohammadi, Niki; Sherman, Jonathan H; Cheng, Xiaoqian; Keidar, Michael

    2015-01-01

    Selectively treating tumor cells is the ongoing challenge of modern cancer therapy. Recently, cold atmospheric plasma (CAP), a near room-temperature ionized gas, has been demonstrated to exhibit selective anticancer behavior. However, the mechanism governing such selectivity is still largely unknown. In this review, the authors first summarize the progress that has been made applying CAP as a selective tool for cancer treatment. Then, the key role of aquaporins in the H2O2 transmembrane diffusion is discussed. Finally, a novel model, based on the expression of aquaporins, is proposed to explain why cancer cells respond to CAP treatment with a greater rise in reactive oxygen species than homologous normal cells. Cancer cells tend to express more aquaporins on their cytoplasmic membranes, which may cause the H2O2 uptake speed in cancer cells to be faster than in normal cells. As a result, CAP treatment kills cancer cells more easily than normal cells. Our preliminary observations indicated that glioblastoma cells consumed H2O2 much faster than did astrocytes in either the CAP-treated or H2O2-rich media, which supported the selective model based on aquaporins. PMID:26700469

  15. Ovarian cancer: Ion channel and aquaporin expression as novel targets of clinical potential.

    Science.gov (United States)

    Frede, Julia; Fraser, Scott P; Oskay-Özcelik, Gülten; Hong, Yeosun; Ioana Braicu, E; Sehouli, Jalid; Gabra, Hani; Djamgoz, Mustafa B A

    2013-07-01

    Ovarian cancer is associated with limited overall survival, due to problems in early detection and therapy. Membrane ion channels have been proposed to play a significant, concerted role in the cancer process, from initial proliferation to metastasis, and promise to be early, functional biomarkers. We review the evidence for ion channel and aquaporin expression and functioning in human ovarian cancer cells and tissues. In vitro, K(+) channels, mainly voltage-gated, including Ca(2+)-activated channels, have been found to control the cell cycle, as in other cancers. Voltage-gated, volume-regulated and intracellular Cl(-) channels have been detected in vitro and in vivo and shown to be involved in proliferation, adhesion and invasion. Evidence for 'transient receptor potential', voltage-gated sodium and calcium channels, which have been shown to contribute to pathogenesis of other carcinomas, is also emerging in ovarian cancer. Aquaporins may be involved in cell growth, migration and formation of ascites via increased water permeability of micro-vessels. It is concluded that functional expression of ion channels and their regulation by steroid hormones and growth factors are an integral part of ovarian cancer development and progression. Furthermore, ion channels may be involved in multidrug resistance, commonly associated with treatment of ovarian cancer. We propose that ion channel studies can facilitate our understanding of the pathobiology of ovarian cancer and, ultimately, can serve as viable novel targets for its clinical management. PMID:23683551

  16. Aquaporin 1 Facilitated Hepatocellular Carcinoma SMMC7221 Cell Migration Associated with Water Permeability

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ai-li; LI Jiang; WANG Yan-qing; ZAKNROU Zohra; MA Tong-hui; LI Xiao-meng

    2011-01-01

    The authors investigated the regulation of human aquaporin l(hAQPl) and the involvement of aquaporin l(AQPl) in the migration of human hepatocellular carcinoma SMMC-7221 cells using RNA intereference technology.Firstly, two short hairpin RNA(shRNA) constructs in PBSU6 vector were reconstructed and their knockdown effects were identified in SMMC-7221 cells. Next, the involvement of endogenous hAQPl in regulating the migration of SMMC-7221 cells was investigated via siRNA technology. HAQPl-shRNA can specifically inhibit AQPl dependent osmotic water permeability. Meanwhile the migration of SMMC-7221 cells was inhibited remarkably after silencing AQPl by performing transwell cell migration assay and in vitro wound healing assay. Furthermore, in the presence of an inhibitor HgCl2, the water permeability of the cell membrane was remarkably decreased, the expression of AQPl was upregulated after HgCl2 treatment and the cell movement was decreased at the moment. Increased AQPl cannot attenuate cell migration ability when cell membrane loses its water permeability function. This demonstrates that the cell migration was remarkably related to the transporting water function of cell membrane.

  17. Importance of NPA motifs in the expression and function of water channel aquaporin-1

    Institute of Scientific and Technical Information of China (English)

    JIANG Yong; MA TongHui

    2007-01-01

    The asparagine-proline-alanine sequences (NPA motifs) are highly conserved in aquaporin water channel family. Crystallographic studies of AQP1 structure demonstrated that the two NPA motifs are in the narrow central constriction of the channel, serving to bind water molecules for selective and efficient water passage. To investigate the importance of the two NPA motifs in the structure, function and biogenesis of aquaporin water channels, we generated AQP1 mutations with NPA1 deletion, NPA2 deletion and NPA1,2 double deletion. The coding sequences of the three mutated cDNAs were subcloned into the mammalian expression vector pcDNA3.1 to form expression plasmids. We established stably transfected CHO cell lines expressing these AQP1 mutants. Immunofluorescence indicated that all the three mutated AQP1 proteins are expressed normally on the plasma membrane of stably transfected CHO cells, suggesting that deletion of NPA motifs does not influence the expression and intracellular processing of AQP1. Functional analysis demonstrated that NPA1 or NPA2 deletion reduced AQP1 water permeability by 49.6% and 46.7%, respectively, while NPA1,2 double deletion had little effect on AQP1 water permeability. These results provide evidence that NPA motifs are important for water per-meation but not essential for the expression, intracellular processing and the basic structure of AQP1 water channel.

  18. Noncanonical binding of calmodulin to aquaporin-0: implications for channel regulation.

    Science.gov (United States)

    Reichow, Steve L; Gonen, Tamir

    2008-09-10

    Aquaporins (AQPs) are a family of ubiquitous membrane channels that conduct water across cell membranes. AQPs form homotetramers containing four functional and independent water pores. Aquaporin-0 (AQP0) is expressed in the eye lens, where its water permeability is regulated by calmodulin (CaM). Here we use a combination of biochemical methods and NMR spectroscopy to probe the interaction between AQP0 and CaM. We show that CaM binds the AQP0 C-terminal domain in a calcium-dependent manner. We demonstrate that only two CaM molecules bind a single AQP0 tetramer in a noncanonical fashion, suggesting a form of cooperativity between AQP0 monomers. Based on these results, we derive a structural model of the AQP0/CaM complex, which suggests CaM may be inhibitory to channel permeability by capping the vestibules of two monomers within the AQP0 tetramer. Finally, phosphorylation within AQP0's CaM binding domain inhibits the AQP0/CaM interaction, suggesting a temporal regulatory mechanism for complex formation. PMID:18786401

  19. Molecular Dynamics Simulation and Bioinformatics Study on Yeast Aquaporin Aqy1 from Pichia pastoris

    Directory of Open Access Journals (Sweden)

    Yubao Cui, David A. Bastien

    2012-01-01

    Full Text Available In the present study, an equilibrated system for the Aqy1 tetramer was developed, and molecular biophysics modeling showed that the Aqy1 channel was blocked by Tyr-31 in the N-terminus, which was also supported by the free energy profiles. However, bioinformatics analysis of the amino acid sequence of Aqy1 indicated this Tyr-31 is not conserved across all fungi. Analysis of the equilibrated structure showed that the central pore along the four-fold axis of the tetramers is formed with hydrophobic amino acid residues. In particular, Phe-90, Trp-198, and Phe-202 form the narrowest part of the pore. Therefore, water molecules are not expected to translocate through the central pore, a hypothesis that we confirmed by molecular dynamics simulations. Each monomer of the Aqy1 tetramers forms a channel whose walls consist mostly of hydrophilic residues, transporting through the selectivity filter containing Arg-227, His-212, Phe-92, and Ala-221, and the two conserved Asn-Pro-Ala (NPA motifs containing asparagines 224 and 112. In summary, not all fungal aquaporins share the same gating mechanism by a tyrosine residue in the N-terminus, and the structural analysis in the present study should aid our understanding of aquaporin structure and its functional implications.

  20. Aquaporin 5 Expression in Mouse Mammary Gland Cells Is Not Driven by Promoter Methylation

    Directory of Open Access Journals (Sweden)

    Barbara Arbeithuber

    2015-01-01

    Full Text Available Several studies have revealed that aquaporins play a role in tumor progression and invasion. In breast carcinomas, high levels of aquaporin 5 (AQP5, a membrane protein involved in water transport, have been linked to increased cell proliferation and migration, thus facilitating tumor progression. Despite the potential role of AQP5 in mammary oncogenesis, the mechanisms controlling mammary AQP5 expression are poorly understood. In other tissues, AQP5 expression has been correlated with its promoter methylation, yet, very little is known about AQP5 promoter methylation in the mammary gland. In this work, we used the mouse mammary gland cell line EpH4, in which we controlled AQP5 expression via the steroid hormone dexamethasone (Dex to further investigate mechanisms regulating AQP5 expression. In this system, we observed a rapid drop of AQP5 mRNA levels with a delay of several hours in AQP5 protein, suggesting transcriptional control of AQP5 levels. Yet, AQP5 expression was independent of its promoter methylation, or to the presence of negative glucocorticoid receptor elements (nGREs in its imminent promoter region, but was rather influenced by the cell proliferative state or cell density. We conclude that AQP5 promoter methylation is not a universal mechanism for AQP5 regulation and varies on cell and tissue type.

  1. Diagnosis of neuromyelitis optica (NMO) spectrum disorders: is MRI obsolete?

    Energy Technology Data Exchange (ETDEWEB)

    Downer, Jonathan James; Carter, Ranjana; Kueker, Wilhelm; Quaghebeur, Gerardine [John Radcliffe Hospital, Department of Neuroradiology, Oxford (United Kingdom); Leite, Maria Isabel; Palace, Jacqueline [Oxford University, Department of Clinical Neurology, Oxford (United Kingdom)

    2012-04-15

    Neuromyelitis optica (NMO) is a severe demyelinating disease that preferentially involves spinal cord and optic nerve. It is part of a spectrum of neurological conditions associated with antibodies to aquaporin-4 (AQP4). This study investigates the role of MRI where novel, more sensitive AQP4 antibody immunoassay techniques are being used. Retrospective review of neuroimaging in 69 patients (25 antibody positive, 44 antibody negative), investigated in the context of suspected NMO or NMO spectrum disorder, was performed independently by two consultant neuroradiologists. Longitudinally extensive, central spinal cord lesions were more frequent in AQP4 positive patients (95.2% vs 35.5%, p < 0.0001; 85.7% vs 45.2%, p = 0.015). Multiple sclerosis diagnostic criteria were less frequently fulfilled on brain MRI in antibody positive patients (5.6% vs 33.3%, p = 0.035). Juxtacortical and corpus callosal lesions were also less common in this group (16.7% vs 46.7%, p = 0.063; 5.6% vs 46.7%, p = 0.0034). Hypothalamic and periependymal disease related to the aqueduct was not seen in antibody negative patients. T1 hypointensity was more common in cord lesions of antibody positive patients (75.0% vs 35.3%, p = 0.037). However, this characteristic did not discriminate antibody positive and negative longitudinally extensive cord lesions (73.3% vs 62.5%, p = 0.66). The NMO spectrum of diseases are among an increasing number of neurological conditions defined by serological tests. However, despite improved immunoassay techniques, MRI of the brain and spinal cord continues to be among the first-line investigations in these patients, providing valuable diagnostic information that will help guide patient management. (orig.)

  2. Atypical presentations of neuromyelitis optica

    Directory of Open Access Journals (Sweden)

    Douglas Sato

    2011-10-01

    Full Text Available Neuromyelitis optica (NMO is an inflammatory disease of central nervous system classically characterized by acute, severe episodes of optic neuritis and longitudinally extensive transverse myelitis, usually with a relapsing course. The identification of an autoantibody exclusively detected in NMO patients against aquaporin-4 (AQP-4 has allowed identification of cases beyond the classical phenotype. Brain lesions, once thought as infrequent, can be observed in NMO patients, but lesions have different characteristics from the ones seen in multiple sclerosis. Additionally, some AQP-4 antibody positive patients may present with a variety of symptoms not being restricted to optic neuritis and acute myelitis during the first attack or in a relapse. Examples are not limited to, but may include patients only with brain and/or brainstem lesions, narcolepsy with hypothalamic lesions or patients with intractable hiccups, nausea and vomiting. The prompt identification of NMO patients with atypical presentations may benefit these patients with institution of early treatment to reduce disability and prevent further attacks.

  3. Light-mediated Kleaf induction and contribution of both the PIP1s and PIP2s aquaporins in five tree species: walnut (Juglans regia) case study

    OpenAIRE

    Ben Baaziz, Khaoula; Lopez, David; Rabot, Amélie; Combes, Didier; Gousset, Aurelie; Bouzid, Sadok; Cochard, Hervé; Sakr, Soulaiman; Venisse, Jean-Stéphane

    2012-01-01

    Understanding the response of leaf hydraulic conductance (Kleaf) to light is a challenge in elucidating plant–water relationships. Recent data have shown that the effect of light on Kleaf is not systematically related to aquaporin regulation, leading to conflicting conclusions. Here we investigated the relationship between light, Kleaf, and aquaporin transcript levels in five tree species (Juglans regia L., Fagus sylvatica L., Quercus robur L., Salix alba L. and Populus tremula L.) grown in t...

  4. Identification and characterization of plasma membrane aquaporins isolated from fiber cells of Calotropis procera.

    Science.gov (United States)

    Aslam, Usman; Khatoon, Asia; Cheema, Hafiza Masooma Naseer; Bashir, Aftab

    2013-07-01

    Calotropis procera, commonly known as "milkweed", possesses long seed trichomes for seed dispersal and has the ability to survive under harsh conditions such as drought and salinity. Aquaporins are water channel proteins expressed in all land plants, divided into five subfamilies plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), NOD26-like proteins (NIPs), small basic intrinsic proteins (SIPs), and the unfamiliar X intrinsic proteins (XIPs). PIPs constitute the largest group of water channel proteins that are involved in different developmental and regulatory mechanisms including water permeability, cell elongation, and stomata opening. Aquaporins are also involved in abiotic stress tolerance and cell expansion mechanisms, but their role in seed trichomes (fiber cells) has never been investigated. A large number of clones isolated from C. procera fiber cDNA library showed sequence homology to PIPs. Both expressed sequence tags (ESTs) and real-time polymerase chain reaction (PCR) studies revealed that the transcript abundance of this gene family in fiber cells of C. procera is greater than that of cotton. Full-length cDNAs of CpPIP1 and CpPIP2 were isolated from C. procera fiber cDNA library and used for constructing plant expression vectors under constitutive (2×35S) and trichome-specific (GhLTP3) promoters. Transgenic tobacco plants were developed via Agrobacterium-mediated transformation. The phenotypic characteristics of the plants were observed after confirming the integration of transgene in plants. It was observed that CpPIP2 expression cassette under 2×35S and GhLTP3 promoter enhanced the numbers of stem and leave trichomes. However, 2×35S::CpPIP2 has a more amplified effect on trichome density and length than GhLTP3::CpPIP2 and other PIP constructs. These findings imply the role of C. procera PIP aquaporins in fiber cell elongation. The PIPs-derived cell expansion mechanism may be exploited through transgenic approaches for

  5. Cloning and characterization of porcine aquaporin 1 water channel expressed extensively in gastrointestinal system

    Institute of Scientific and Technical Information of China (English)

    Shun-Ying Jin; Yan-Li Liu; Li-Na Xu; Yong Jiang; Ying Wang; Bao-Xue Yang; Hong Yang; Tong-Hui Ma

    2006-01-01

    AIM: To clone and characterize the porcine aquaporins (AQPs) in the gastrointestinal system.METHODS: A PCR-based cloning strategy and RACE were used to clone full-length AQP coding sequence from reversely transcribed pig liver cDNA. Stopped-flow light scattering and a YFP-based fluorescence method were used to measure the osmotic water permeability of erythrocytes and the stably transfected CHO cells.RT-PCR, Northern blot, and immunohistochemistry were used to determine the gastrointestinal expression and localization of cloned AQPs. Protein expression in transfected cells and red blood cells was analyzed by Western blot.RESULTS: An 813 bp cDNA encoding a 271 amino acid porcine aquaporin (designated pAQP1) was cloned from liver mRNA (pAQP1 has a 93% identity with human AQP1 and contains two NPA motifs conserved in AQP family, one consensus sequence for N-linked glycosylation, and one mercury-sensitive site at cysteine 191). RT-PCR analysis revealed extensive expression of pAQP1 mRNA in porcine digestive glands and gut.Northern blot showed a single 3.0 kb transcript in selected digestive organs, pAQP1 protein was localized at central lacteals of the small intestine, microvessles of salivary glands, as well as epithelium of intrahepatic bile ducts by immunoperoxydase. High osmotic water permeability that is inhibitable by HgCl2 was detected in porcine erythrocytes and CHO cells stably transfected with pAQP1 cDNA. Tmmunoblot analysis of porcine erythrocytes and pAQP-transfected CHO cells revealed an unglycosylated 28 ku band and larger glycosylated proteins.CONCLUSION: pAQP1 is the first porcine aquaporin that can be molecularly identified so far. The broad distribution of pAQP1 in epithelium and endothelium of porcine digestive organs may suggest an important role of channel-mediated water transport in fluid secretion/absorption as well as in digestive function and pathophysiology of the gastrointestinal system.

  6. Identification and characterization of plasma membrane aquaporins isolated from fiber cells of Calotropis procera

    Institute of Scientific and Technical Information of China (English)

    Usman ASLAM; Asia KHATOON; Hafiza Masooma Naseer CHEEMA; Aftab BASHIR

    2013-01-01

    Calotropis procera,commonly known as "milkweed",possesses long seed trichomes for seed dispersal and has the ability to survive under harsh conditions such as drought and salinity.Aquaporins are water channel proteins expressed in all land plants,divided into five subfamilies plasma membrane intrinsic proteins (PIPs),tonoplast intrinsic proteins (TIPs),NOD26-1ike proteins (NIPs),small basic intrinsic proteins (SIPs),and the unfamiliar X intrinsic proteins (XlPs).PIPs constitute the largest group of water channel proteins that are involved in different developmental and regulatory mechanisms including water permeability,cell elongation,and stomata opening.Aquaporins are also involved in abiotic stress tolerance and cell expansion mechanisms,but their role in seed trichomes (fiber cells) has never been investigated.A large number of clones isolated from C.procera fiber cDNA library showed sequence homology to PIPs.Both expressed sequence tags (ESTs) and real-time polymerase chain reaction (PCR) studies revealed that the transcript abundance of this gene family in fiber cells of C.procera is greater than that of cotton.Full-length cDNAs of CpPIP1 and CpPIP2 were isolated from C.procera fiber cDNA library and used for constructing plant expression vectors under constitutive (2x35S) and trichome-specific (GhLTP3) promoters.Transgenic tobacco plants were developed via Agrobacterium-mediated transformation.The phenotypic characteristics of the plants were observed after confirming the integration of transgene in plants.It was observed that CpPIP2 expression cassette under 2x35S and GhLTP3 promoter enhanced the numbers of stem and leave trichomes.However,2x35S::CpPIP2 has a more amplified effect on trichome density and length than GhLTP3::CpPIP2 and other PIP constructs.These findings imply the role of C.procera PIP aquaporins in fiber cell elongation.The PIPs-derived cell expansion mechanism may be exploited through transgenic approaches for improvement of fiber staple

  7. Herbivory of maize by southern corn rootworm induces expression of the major intrinsic protein ZmNIP1;1 and leads to the discovery of a novel aquaporin ZmPIP2;8

    OpenAIRE

    Lawrence, Susan D.; Novak, Nicole G.; Xu, Hao; Cooke, Janice E. K.

    2013-01-01

    Aquaporins channel water and other neutral molecules through cell membranes. Aquaporin gene expression is subject to transcriptional control and can be modulated by factors affecting water balance such as salt, abscisic acid and drought. During infestation of maize by southern corn rootworm (SCR), an insect that chews into and significantly damages maize roots, three maize aquaporins were differentially expressed upon prolonged infestation. Using a brief infestation of maize roots ZmNIP1;1 tr...

  8. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, or ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are metastatic, ...

  9. Brain Basics

    Medline Plus

    Full Text Available ... Basics will introduce you to some of this science, such as: How the brain develops How genes and the environment affect the brain The basic structure of the brain How different parts of the brain communicate and work with each other How changes in the brain ...

  10. Brain Tumors

    Science.gov (United States)

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  11. Brain Fingerprinting

    Directory of Open Access Journals (Sweden)

    ravi kumar

    2012-12-01

    Full Text Available Brain Fingerprinting is a scientific technique to determine whether or not specific information is stored in an individual's brain by measuring a electrical brain wave response to Word, phrases, or picture that are presented on computer screen. Brain Fingerprinting is a controversial forensic science technique that uses electroencephalograph y (EEG to determine whether specific information is stored in a subject's brain

  12. 临床孤立综合征转归为视神经脊髓炎的相关因素分析%Correlative factor analysis for clinically isolated syndrome turning to neuromyelitis optica

    Institute of Scientific and Technical Information of China (English)

    郭海霞; 张美妮; 郝洪军

    2012-01-01

    目的 探讨临床孤立综合征(CIS)转归为视神经脊髓炎(NMO)的影响因素.方法 收集2004-09-2011-09就诊于作者医院神经内科CIS患者109例.回顾性分析所有患者首次发病时头颅和脊髓MRI特点及临床表现.采用酶联免疫吸附法(ELISA)检测血清水通道蛋白4抗体(AQP4-Ab)水平,另备30份健康者血清作为健康对照组,以高于健康对照组血清AQP4-Ab浓度的均值+3倍标准差者为阳性.结果 (1)随访0.5~7年,中位数为3.0年,四分位数间距为4.6年,转归为NMO 46例,转归为多发性硬化(MS)29例,其余仍是CIS,包括24例脊髓炎,10例视神经炎(ON).(2)转归为NMO组血清AQP4-Ab水平明显高于MS组、脊髓炎组、ON组和健康对照组(P<0.05).(3)转归为NMO组AQP4-Ab阳性率为63.03%(29/46),高于转归为MS组的13.79%(4/29)、脊髓炎组的29.17%(7/24)、ON组的20.00%(2/10),差异均有统计学意义(P<0.05).(4)多因素分析结果提示:AQP4-Ab阳性、NMO颅内典型病灶、脊髓损伤>3个节段、扩展残疾状态量表(EDSS)与CIS转归为NMO有关.结论 AQP4-Ab阳性、NMO颅内典型病灶或者脊髓损伤>3个节段、EDSS评分对预测CIS转归为NMO有临床价值.%Objective To explore influential factors for the evolution of clinically isolated syndrome (CIS) to optic nerve myelitis (NMO). Methods One hundred and nine patients with CIS were included in author' s hospital form Sep 2004 to Nov 2011. Brain and spinal cord MRI characteristics and clinical manifestations were retrospectively analyzed among all of the patients on the first attack. 30 healthy subjects were taken as normal controls and their serum were collected. Serum aquaporin-4 antibody (AQP4-Ab) level was detected with Enzyme-linked Immunosorbent Assay (ELISA). The serum AQP4-Ab level higher than the mean value of normal control group plus 3 times of standard deviation was regarded as positive. Results (1) All the patients were followed up for 0. 5 tp 7 years, with a

  13. Aquaporins in the Colon as a New Therapeutic Target in Diarrhea and Constipation

    Science.gov (United States)

    Ikarashi, Nobutomo; Kon, Risako; Sugiyama, Kiyoshi

    2016-01-01

    Aquaporins (AQPs) play important roles in the water transport system in the human body. There are currently 13 types of AQP, AQP0 through AQP12, which are expressed in various organs. Many members of the AQP family are expressed in the intestinal tract. AQP3 is predominantly expressed in the colon, ultimately controlling the water transport. Recently, it was clarified that several laxatives exhibit a laxative effect by changing the AQP3 expression level in the colon. In addition, it was revealed that morphine causes severe constipation by increasing the AQP3 expression level in the colon. These findings have shown that AQP3 is one of the most important functional molecules in water transport in the colon. This review will focus on the physiological and pathological roles of AQP3 in the colon, and discuss clinical applications of colon AQP3. PMID:27447626

  14. Impact of monoolein on aquaporin1-based supported lipid bilayer membranes

    Science.gov (United States)

    Wang, Zhining; Wang, Xida; Ding, Wande; Wang, Miaoqi; Qi, Xin; Gao, Congjie

    2015-08-01

    Aquaporin (AQP) based biomimetic membranes have attracted considerable attention for their potential water purification applications. In this paper, AQP1 incorporated biomimetic membranes were prepared and characterized. The morphology and structure of the biomimetic membranes were characterized by in situ atomic force microscopy (AFM), infrared absorption spectroscopy, fluorescence microscopy, and contact angle measurements. The nanofiltration performance of the AQP1 incorporated membranes was investigated at 4 bar by using 2 g l-1 NaCl as feed solution. Lipid mobility plays an important role in the performance of the AQP1 incorporated supported lipid bilayer (SLB) membranes. We demonstrated that the lipid mobility is successfully tuned by the addition of monoolein (MO). Through in situ AFM and fluorescence recovery after photo-bleaching (FRAP) measurements, the membrane morphology and the molecular mobility were studied. The lipid mobility increased in the sequence DPPC rejection. This study may provide some useful insights for improving the water purification performance of biomimetic membranes.

  15. Fouling Characterization of Forward Osmosis Biomimetic Aquaporin Membranes Used for Water Recovery from Municipal Wastewater

    DEFF Research Database (Denmark)

    Zarebska, Agata; Petrinic, Irena; Hey, Tobias;

    Generally more than 99.93% of municipal wastewater is composed of water, therefore water recovery can alleviate global water stress which currently exists. Traditional ways to extract water from wastewater by the use of membrane bioreactors combined with reverse osmosis (RO), or micro....../ultrafiltration coupled with RO and sand filtration, or advanced oxidation process require high energy. Contrary to pressure driven membrane processes, forward osmosis (FO) offers advantages such as no need of high hydraulic pressure, reduced fouling and simple cleaning. Even though fouling of FO membranes is less severe......, organic, and biological fouling, membrane characterization is not a trivial task. The aim of this work is to characterize fouling of FO biomimetic aquaporin membranes during water recovery from municipal wastewater. Membrane fouling was characterized using Scanning Electron Microscopy, X-ray Dispersive...

  16. Stimulation of aquaporin-5 and transepithelial water permeability in human airway epithelium by hyperosmotic stress

    DEFF Research Database (Denmark)

    Pedersen, Peter Steen; Braunstein, Thomas Hartig; Jørgensen, Anders;

    2006-01-01

    Osmotic water permeability (P(f )) was measured in spheroid-shaped human nasal airway epithelial explants pre-exposed to increasing levels of hyperosmotic stress. The fluid-filled spheroids, derived from nasal polyps, were lined by a single cell layer with the ciliated apical cell membrane facing......-CF spheroids and were not significantly influenced by hyperosmotic stress. The results suggest that hyperosmotic stress is an important activator of AQP-5 in human airway epithelium, leading to significantly increased transepithelial water permeability....... of aquaporin-5 (AQP5), studied by immunofluorescence and confocal microscopy, showed an increase in parallel with the increase in P(f ) following hyperosmotic stress. The AQP5 was localized both in cytoplasmic vesicles and in apical cell membranes. Spontaneous fluid absorption rates were equal in CF and non...

  17. Control of the selectivity of the aquaporin water channel family by global orientational tuning

    DEFF Research Database (Denmark)

    Jensen, Morten Østergaard; Tajkhorshid, E.; Nollert, P.;

    2002-01-01

    Aquaporins are transmembrane channels found in cell membranes of all life forms. We examine their apparently paradoxical property, facilitation of efficient permeation of water while excluding protons, which is of critical importance to preserving the electrochemical potential across the cell......, this dictates opposite orientations of water molecules in the two halves of the channel, and thus prevents the formation of a "proton wire," while permitting rapid water diffusion. Both simulations and observations revealed a more regular distribution of channel water and an increased water permeability...... membrane. We have determined the structure of the Escherichia coli aquaglyceroporin GlpF with bound water, in native (2.7 angstroms) and in W48F/F200T mutant (2.1 angstroms) forms, and carried out 12-nanosecond molecular dynamics simulations that define the spatial and temporal probability distribution...

  18. Experimental Evaluation of Proposed Small-Molecule Inhibitors of Water Channel Aquaporin-1.

    Science.gov (United States)

    Esteva-Font, Cristina; Jin, Byung-Ju; Lee, Sujin; Phuan, Puay-Wah; Anderson, Marc O; Verkman, A S

    2016-06-01

    The aquaporin-1 (AQP1) water channel is a potentially important drug target, as AQP1 inhibition is predicted to have therapeutic action in edema, tumor growth, glaucoma, and other conditions. Here, we measured the AQP1 inhibition efficacy of 12 putative small-molecule AQP1 inhibitors reported in six recent studies, and one AQP1 activator. Osmotic water permeability was measured by stopped-flow light scattering in human and rat erythrocytes that natively express AQP1, in hemoglobin-free membrane vesicles from rat and human erythrocytes, and in plasma membrane vesicles isolated from AQP1-transfected Chinese hamster ovary cell cultures. As a positive control, 0.3 mM HgCl2 inhibited AQP1 water permeability by >95%. We found that none of the tested compounds at 50 µM significantly inhibited or increased AQP1 water permeability in these assays. Identification of AQP1 inhibitors remains an important priority. PMID:26993802

  19. Water deprivation up-regulates urine osmolality and renal aquaporin 2 in Mongolian gerbils (Meriones unguiculatus).

    Science.gov (United States)

    Xu, Meng-Meng; Wang, De-Hua

    2016-04-01

    To better understand how desert rodents adapt to water scarcity, we examined urine osmolality, renal distribution and expression of aquaporins (AQPs) in Mongolian gerbils (Meriones unguiculatus) during 7 days of water deprivation (WD). Urine osmolality of the gerbils during WD averaged 7503 mOsm kg(-1). Renal distributions of AQP1, AQP2, and AQP3 were similar to that described in other rodents. After the 7 day WD, renal AQP2 was up-regulated, while resting metabolic rate and total evaporative water loss decreased by 43% and 36%, respectively. Our data demonstrated that Mongolian gerbils showed high urine concentration, renal AQPs expression and body water conservation to cope with limited water availability, which may be critical for their survival during dry seasons in cold deserts. PMID:26806059

  20. Neuro-ophthalmic manifestation of neuromyelitis optica spectrum disorders

    Directory of Open Access Journals (Sweden)

    Xiao-jun ZHANG

    2014-10-01

    Full Text Available Neuromyelitis optica spectrum disorders (NMOSDs include classic neuromyelitis optica (NMO, opticospinal multiple sclerosis (OSMS, limited form of NMO and isolated optic neuritis or myelitis accompanied by either systemic autoimmune diseases or typical MRI findings of NMO. The common neuro-ophthalmic features of NMOSDs include simultaneous or consecutive bilateral optic neuritis, more commonly seen optic disk edema and surrounding exudate, poor visual recovery, steroid responsiveness and dependency. Combined with serum aquaporin 4 (AQP4 antibody and brain MRI examination, these clinical features can be helpful to the early differential diagnosis between NMOSDs and MS. Some types of eye movement abnormalities have been reported in patients with NMOSDs, but further investigation needs to be done before the specificity of these features are confirmed. doi: 10.3969/j.issn.1672-6731.2014.10.003

  1. Brain Basics

    Medline Plus

    Full Text Available ... The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the ... distant nerve cells (via axons) to form brain circuits. These circuits control specific body functions such as ...

  2. Brain Basics

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    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies ...

  3. Brain Basics

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    Full Text Available ... Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... others live with symptoms of mental illness every day. They can be moderate, or serious and cause ...

  4. Brain Basics

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    Full Text Available ... helps Sarah to better cope with her feelings. Brain Research Modern research tools and techniques are giving scientists ... the treatment for a person's specific conditions. Such brain research help increase the understanding of how the brain ...

  5. Brain Basics

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    Full Text Available ... little dopamine or problems using dopamine in the thinking and feeling regions of the brain may play ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses ...

  6. Brain Basics

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    Full Text Available ... as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are the basic working unit of the brain ... specialized for the function of conducting messages. A neuron has three basic parts: Cell body which includes ...

  7. Brain Malformations

    Science.gov (United States)

    Most brain malformations begin long before a baby is born. Something damages the developing nervous system or causes it ... medicines, infections, or radiation during pregnancy interferes with brain development. Parts of the brain may be missing, ...

  8. Brain Basics

    Medline Plus

    Full Text Available ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ... grow there are differences in brain development in children who develop bipolar disorder than children who do ...

  9. Brain Basics

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    Full Text Available ... Basics will introduce you to some of this science, such as: How the brain develops How genes and the environment affect the brain The basic structure of the brain How different parts of ...

  10. Brain Basics

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    Full Text Available ... understanding of the brain than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures ...

  11. Brain Basics

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    Full Text Available ... science, such as: How the brain develops How genes and the environment affect the brain The basic ... that with brain development in people mental disorders. Genes and environmental cues both help to direct this ...

  12. Brain surgery

    Science.gov (United States)

    Craniotomy; Surgery - brain; Neurosurgery; Craniectomy; Stereotactic craniotomy; Stereotactic brain biopsy; Endoscopic craniotomy ... cut depends on where the problem in the brain is located. The surgeon creates a hole in ...

  13. Aquaporin 3 (AQP3 participates in the cytotoxic response to nucleoside-derived drugs

    Directory of Open Access Journals (Sweden)

    Trigueros-Motos Laia

    2012-09-01

    Full Text Available Abstract Background Nucleoside analogs used in the chemotherapy of solid tumors, such as the capecitabine catabolite 5′-deoxy-5-fluorouridine (5′-DFUR trigger a transcriptomic response that involves the aquaglyceroporin aquaporin 3 along with other p53-dependent genes. Here, we examined whether up-regulation of aquaporin 3 (AQP3 mRNA in cancer cells treated with 5′-DFUR represents a collateral transcriptomic effect of the drug, or conversely, AQP3 participates in the activity of genotoxic agents. Methods The role of AQP3 in cell volume increase, cytotoxicity and cell cycle arrest was analyzed using loss-of-function approaches. Results 5′-DFUR and gemcitabine, but not cisplatin, stimulated AQP3 expression and cell volume, which was partially and significantly blocked by knockdown of AQP3. Moreover, AQP3 siRNA significantly blocked other effects of nucleoside analogs, including G1/S cell cycle arrest, p21 and FAS up-regulation, and cell growth inhibition. Short incubations with 5-fluorouracil (5-FU also induced AQP3 expression and increased cell volume, and the inhibition of AQP3 expression significantly blocked growth inhibition triggered by this drug. To further establish whether AQP3 induction is related to cell cycle arrest and apoptosis, cells were exposed to long incubations with escalating doses of 5-FU. AQP3 was highly up-regulated at doses associated with cell cycle arrest, whereas at doses promoting apoptosis induction of AQP3 mRNA expression was reduced. Conclusions Based on the results, we propose that the aquaglyceroporin AQP3 is required for cytotoxic activity of 5’-DFUR and gemcitabine in the breast cancer cell line MCF7 and the colon adenocarcinoma cell line HT29, and is implicated in cell volume increase and cell cycle arrest.

  14. Cardiac Morphology and Function, and Blood Gas Transport in Aquaporin-1 Knockout Mice

    Science.gov (United States)

    Al-Samir, Samer; Wang, Yong; Meissner, Joachim D.; Gros, Gerolf; Endeward, Volker

    2016-01-01

    We have studied cardiac and respiratory functions of aquaporin-1-deficient mice by the Pressure-Volume-loop technique and by blood gas analysis. In addition, the morphological properties of the animals' hearts were analyzed. In anesthesia under maximal dobutamine stimulation, the mice exhibit a moderately elevated heart rate of < 600 min−1 and an O2 consumption of ~0.6 ml/min/g, which is about twice the basal rate. In this state, which is similar to the resting state of the conscious animal, all cardiac functions including stroke volume and cardiac output exhibited resting values and were identical between deficient and wildtype animals. Likewise, pulmonary and peripheral exchange of O2 and CO2 were normal. In contrast, several morphological parameters of the heart tissue of deficient mice were altered: (1) left ventricular wall thickness was reduced by 12%, (2) left ventricular mass, normalized to tibia length, was reduced by 10–20%, (3) cardiac muscle fiber cross sectional area was decreased by 17%, and (4) capillary density was diminished by 10%. As the P-V-loop technique yielded normal end-diastolic and end-systolic left ventricular volumes, the deficient hearts are characterized by thin ventricular walls in combination with normal intraventricular volumes. The aquaporin-1-deficient heart thus seems to be at a disadvantage compared to the wild-type heart by a reduced left-ventricular wall thickness and an increased diffusion distance between blood capillaries and muscle mitochondria. While under the present quasi-resting conditions these morphological alterations have no consequences for cardiac function, we expect that the deficient hearts will show a reduced maximal cardiac output. PMID:27252655

  15. Aquaporin 2-increased renal cell proliferation is associated with cell volume regulation.

    Science.gov (United States)

    Di Giusto, Gisela; Flamenco, Pilar; Rivarola, Valeria; Fernández, Juan; Melamud, Luciana; Ford, Paula; Capurro, Claudia

    2012-12-01

    We have previously demonstrated that in renal cortical collecting duct cells (RCCD(1)) the expression of the water channel Aquaporin 2 (AQP2) raises the rate of cell proliferation. In this study, we investigated the mechanisms involved in this process, focusing on the putative link between AQP2 expression, cell volume changes, and regulatory volume decrease activity (RVD). Two renal cell lines were used: WT-RCCD(1) (not expressing aquaporins) and AQP2-RCCD(1) (transfected with AQP2). Our results showed that when most RCCD(1) cells are in the G(1)-phase (unsynchronized), the blockage of barium-sensitive K(+) channels implicated in rapid RVD inhibits cell proliferation only in AQP2-RCCD(1) cells. Though cells in the S-phase (synchronized) had a remarkable increase in size, this enhancement was higher and was accompanied by a significant down-regulation in the rapid RVD response only in AQP2-RCCD(1) cells. This decrease in the RVD activity did not correlate with changes in AQP2 function or expression, demonstrating that AQP2-besides increasing water permeability-would play some other role. These observations together with evidence implying a cell-sizing mechanism that shortens the cell cycle of large cells, let us to propose that during nutrient uptake, in early G(1), volume tends to increase but it may be efficiently regulated by an AQP2-dependent mechanism, inducing the rapid activation of RVD channels. This mechanism would be down-regulated when volume needs to be increased in order to proceed into the S-phase. Therefore, during cell cycle, a coordinated modulation of the RVD activity may contribute to accelerate proliferation of cells expressing AQP2. PMID:22786728

  16. Aquaporin 3 (AQP3) participates in the cytotoxic response to nucleoside-derived drugs

    International Nuclear Information System (INIS)

    Nucleoside analogs used in the chemotherapy of solid tumors, such as the capecitabine catabolite 5′-deoxy-5-fluorouridine (5′-DFUR) trigger a transcriptomic response that involves the aquaglyceroporin aquaporin 3 along with other p53-dependent genes. Here, we examined whether up-regulation of aquaporin 3 (AQP3) mRNA in cancer cells treated with 5′-DFUR represents a collateral transcriptomic effect of the drug, or conversely, AQP3 participates in the activity of genotoxic agents. The role of AQP3 in cell volume increase, cytotoxicity and cell cycle arrest was analyzed using loss-of-function approaches. 5′-DFUR and gemcitabine, but not cisplatin, stimulated AQP3 expression and cell volume, which was partially and significantly blocked by knockdown of AQP3. Moreover, AQP3 siRNA significantly blocked other effects of nucleoside analogs, including G1/S cell cycle arrest, p21 and FAS up-regulation, and cell growth inhibition. Short incubations with 5-fluorouracil (5-FU) also induced AQP3 expression and increased cell volume, and the inhibition of AQP3 expression significantly blocked growth inhibition triggered by this drug. To further establish whether AQP3 induction is related to cell cycle arrest and apoptosis, cells were exposed to long incubations with escalating doses of 5-FU. AQP3 was highly up-regulated at doses associated with cell cycle arrest, whereas at doses promoting apoptosis induction of AQP3 mRNA expression was reduced. Based on the results, we propose that the aquaglyceroporin AQP3 is required for cytotoxic activity of 5’-DFUR and gemcitabine in the breast cancer cell line MCF7 and the colon adenocarcinoma cell line HT29, and is implicated in cell volume increase and cell cycle arrest

  17. An aquaporin PvTIP4;1 from Pteris vittata may mediate arsenite uptake.

    Science.gov (United States)

    He, Zhenyan; Yan, Huili; Chen, Yanshan; Shen, Hongling; Xu, Wenxiu; Zhang, Haiyan; Shi, Lei; Zhu, Yong-Guan; Ma, Mi

    2016-01-01

    The fern Pteris vittata is an arsenic hyperaccumulator. The genes involved in arsenite (As(III)) transport are not yet clear. Here, we describe the isolation and characterization of a new P. vittata aquaporin gene, PvTIP4;1, which may mediate As(III) uptake. PvTIP4;1 was identified from yeast functional complement cDNA library of P. vittata. Arsenic toxicity and accumulating activities of PvTIP4;1 were analyzed in Saccharomyces cerevisiae and Arabidopsis. Subcellular localization of PvTIP4;1-GFP fusion protein in P. vittata protoplast and callus was conducted. The tissue expression of PvTIP4;1 was investigated by quantitative real-time PCR. Site-directed mutagenesis of the PvTIP4;1 aromatic/arginine (Ar/R) domain was studied. Heterologous expression in yeast demonstrates that PvTIP4;1 was able to facilitate As(III) diffusion. Transgenic Arabidopsis showed that PvTIP4;1 increases arsenic accumulation and induces arsenic sensitivity. Images and FM4-64 staining suggest that PvTIP4;1 localizes to the plasma membrane in P. vittata cells. A tissue location study shows that PvTIP4;1 transcripts are mainly expressed in roots. Site-directed mutation in yeast further proved that the cysteine at the LE1 position of PvTIP4;1 Ar/R domain is a functional site. PvTIP4;1 is a new represented tonoplast intrinsic protein (TIP) aquaporin from P. vittata and the function and location results imply that PvTIP4;1 may be involved in As(III) uptake. PMID:26372374

  18. A decrease in the permeability of aquaporin zero as a possible cause for presbyopia.

    Science.gov (United States)

    Gerometta, R; Candia, O A

    2016-01-01

    The crystalline lens appears to be a simple organ with the sole role of focusing light upon the retina. However, numerous studies have underscored its dynamic nature with a host of compartmentalized physiological processes. As the individual ages, the normal lens develops two inescapable processes, presbyopia and cataracts. Yet, to date, there is no uniform explanation for presbyopia and many factors have been proposed as contributors including continuous enlargement of the lens, loss of power of the ciliary muscle and hardening of the lens fibers. Proposed explanations are incomplete and need experimental confirmation. This paper analyzes the possible causes for presbyopia and proposes a new one for it: a decrease in the permeability of aquaporin zero (AQP-0) also known as major intrinsic protein (MIP). Based on original findings of our laboratory, this paper proposes that a fluid flow exists inside the avascular lens. This fluid enters and leaves the lens during the accommodation process. We believe that for this to occur the lens utilizes the permeability of aquaporin zero which is abundant in the membrane of the fiber cells. Volume change due to fluid traversing the surface of the lens occurs during accommodation. We present the hypothesis that increasing the permeability of AQP-0 would facilitate accommodation. Therefore, defects in AQP-0 permeability may be a cause for presbyopia. We would also like to propose that it is possible to visualize and measure the fluid volume lost during un-accommodation and determine if the fluid is lost across the anterior, posterior or both surfaces. An age-related loss in lens water permeability could reduce fluid fluxes during the shape changes of accommodation potentially contributing to presbyopia. PMID:26615967

  19. Brain mapping

    OpenAIRE

    Blaž Koritnik

    2004-01-01

    Cartography of the brain ("brain mapping") aims to represent the complexities of the working brain in an understandable and usable way. There are four crucial steps in brain mapping: (1) acquiring data about brain structure and function, (2) transformation of data into a common reference, (3) visualization and interpretation of results, and (4) databasing and archiving. Electrophysiological and functional imaging methods provide information about function of the human brain. A prere...

  20. Seronegative Neuromyelitis Optica: A Case Report of a Hispanic Male

    Directory of Open Access Journals (Sweden)

    Nabeel Badri

    2016-05-01

    Full Text Available Neuromyelitis optica (NMO is a rare disease, common in white females and rarely reported in Hispanic males. It is usually associated with recurrent demyelinating spectrum that is autoimmune in nature. The diagnosis is usually confirmed by antibody biomarkers; however, they can be negative and lead to more dilemma in diagnosis. Furthermore, the course of disease and prognosis are different in seronegative as compared to seropositive NMO. Treatment is similar in both subgroups with new approaches under investigation for seronegative NMO patients. We present an interesting case of a 37-year-old Hispanic male who presented with sudden onset of lower extremity weakness, numbness, blurry vision, and urinary retention. Magnetic resonance imaging (MRI of the thoracic spine showed multiphasic demyelinating process involving the thoracic spinal cord. His brain MRI also revealed changes suggesting optic neuritis. The patient met the criteria for diagnosis of NMO by having optic neuritis and myelitis by imaging studies despite having negative aquaporin-4 antibodies (AQP4-Ab. His condition improved after plasma exchange. NMO can be difficult to distinguish from acute multiple sclerosis in the early stages of the disease. Having AQP4-Ab testing is important for diagnosis with imaging studies; however, negative antibody results cannot exclude the diagnosis, but rather group it in seronegative subtype. Ongoing studies and research suggest that seronegative NMO might have a different pathophysiology, manifestation, and prognosis.

  1. Neuromyelitis optica IgG stimulates an immunological response in rat astrocyte cultures

    Institute of Scientific and Technical Information of China (English)

    Howe CL; Kaptzan T; Magaa SM; Ayers-Ringler JR; LaFrance-Corey RG; Lucchinetti CF

    2014-01-01

    Neuromyelitis optica (NMO) is a primary astrocyte disease associated with central nervous system inflammation, demyelination, and tissue injury. Brain lesions are frequently observed in regions enriched in expression of the aquaporin-4 (AQP4) water channel, an antigenic target of the NMO IgG serologic marker. Based on observations of disease reversibility and careful characterization of NMO lesion development, we propose that the NMO IgG may induce a dynamic immunological response in astrocytes. Using primary rat astrocyte-enriched cultures and treatment with NMO patient-derived serum or purified IgG, we observed a robust pattern of gene expression changes consistent with the induction of a reactive and inflammatory phenotype in astrocytes. The reactive astrocyte factor lipocalin-2 and a broad spectrum of chemokines, cytokines, and stress response factors were induced by either NMO patient serum or purified IgG. Treatment with IgG from healthy controls had no effect. The effect is disease-specific, as serum from patients with relapsing-remitting multiple sclerosis, Sj gren's, or systemic lupus erythematosus did not induce a response in the cultures. We hypothesize that binding of the NMO IgG to AQP4 induces a cellular response that results in transcriptional and translational events within the astrocyte that are consistent with a reactive and inflammatory phenotype. Strategies aimed at reducing the inflammatory response of astrocytes may short circuit an amplification loop associated with NMO lesion development.

  2. Myopathy associated with neuromyelitis optica spectrum disorders.

    Science.gov (United States)

    He, Dian; Li, Ya; Dai, Qingqing; Zhang, Yifan; Xu, Zhu; Li, Yuan; Cai, Gang; Chu, Lan

    2016-10-01

    Neuromyelitis optica spectrum disorders (NMOSD) were generally thought to affect only central nervous system and spare peripheral aquaporin-4 (AQP4)-expressing organs. In recent years, however, increasing evidence has shown that skeletal muscle is involved in NMOSD. We provided a comprehensive review of the relevant literature and summarized the clinical and pathological characteristics of myopathy associated with NMOSD. NMOSD-associated myopathy seems to be characterized by mild muscle symptoms with prominent hyperCKemia and minimal changes on conventional pathological staining. Loss of AQP4 and deposition of IgG and activated complement products on sarcolemma of type II fibers are diagnostic features on immunohistochemical examinations. Creatine kinase leakage as a result of AQP4-IgG-induced, complement-mediated sarcolemmal injury may be a potential mechanism for hyperCKemia. Myopathy should be considered a component of NMOSD unified by AQP4-IgG seropositivity. PMID:26514543

  3. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

    Directory of Open Access Journals (Sweden)

    Jarius Sven

    2012-01-01

    Full Text Available Abstract Background The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab in patients with neuromyelitis optica spectrum disorders (NMOSD has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. Objective To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. Methods Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%. Results Seropositive patients were found to be predominantly female (p 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome. Conclusion This study provides an overview of the clinical and paraclinical features of NMOSD in Caucasians and demonstrates a number of distinct disease characteristics in seropositive and seronegative patients.

  4. Development of supported biomimetic membranes for insertion of aquaporin protein water channels for novel water filtration applications

    DEFF Research Database (Denmark)

    Hansen, Jesper Søndergaard

    Aquaporins represent a class of membrane protein channels found in all living organisms that selectively transport water molecules across biological membranes. The work presented in this thesis was motivated by the conceptual idea of incorporating aquaporin water channels into biomimetic membranes...... to develop novel water separation technologies. To accomplish this, it is necessary to construct an efficient platform to handle biomimetic membranes. Moreover, general methods are required to reliable and controllable reconstitute membrane proteins into artificially made model membranes. These are...... the topics of this thesis, and are divided into three main chapters. Chapter 2 reviews recent advances in the design and construction of biomimetic membrane arrays. Moreover, current and novel strategies for the reconstitution of membrane proteins into biomimetic membranes are reviewed. Chapter 3...

  5. Human Aquaporin 4 Gating Dynamics under Perpendicularly-Oriented Electric-Field Impulses: A Molecular Dynamics Study.

    Science.gov (United States)

    Marracino, Paolo; Liberti, Micaela; Trapani, Erika; Burnham, Christian J; Avena, Massimiliano; Garate, José-Antonio; Apollonio, Francesca; English, Niall J

    2016-01-01

    Human aquaporin 4 has been studied using molecular dynamics (MD) simulations in the absence and presence of pulses of external static electric fields. The pulses were 10 ns in duration and 0.012-0.065 V/Å in intensity acting along both directions perpendicular to the pores. Water permeability and the dipolar response of all residues of interest (including the selectivity filter) within the pores have been studied. Results showed decreased levels of water osmotic permeability within aquaporin channels during orthogonally-oriented field impulses, although care must be taken with regard to statistical certainty. This can be explained observing enhanced "dipolar flipping" of certain key residues, especially serine 211, histidine 201, arginine 216, histidine 95 and cysteine 178. These residues are placed at the extracellular end of the pore (serine 211, histidine 201, and arginine 216) and at the cytoplasm end (histidine 95 and cysteine 178), with the key role in gating mechanism, hence influencing water permeability. PMID:27428954

  6. Expression and subcellular localization of aquaporin water channels in the polarized hepatocyte cell line, WIF-B

    OpenAIRE

    Marinelli Raúl A; Splinter Patrick L; Tietz Pamela S; Gradilone Sergio A; LaRusso Nicholas F

    2005-01-01

    Abstract Background Recent data suggest that canalicular bile secretion involves selective expression and coordinated regulation of aquaporins (AQPs), a family of water channels proteins. In order to further characterize the role of AQPs in this process, an in vitro cell system with retained polarity and expression of AQPs and relevant solute transporters involved in bile formation is highly desirable. The WIF-B cell line is a highly differentiated and polarized rat hepatoma/human fibroblast ...

  7. Concurrent expression of erythroid and renal aquaporin CHIP and appearance of water channel activity in perinatal rats.

    OpenAIRE

    Smith, B L; Baumgarten, R; Nielsen, S; D. Raben; Zeidel, M L; Agre, P

    1993-01-01

    Major phenotypic changes occur in red cell membranes during the perinatal period, but the underlying molecular explanations remain poorly defined. Aquaporin CHIP, the major erythroid and renal water channel, was studied in perinatal rats using affinity-purified anti-CHIP IgG for immunoblotting, flow cytometry, and immunofluorescence microscopy. CHIP was not detected in prenatal red cells but was first identified in circulating red cells on the third postnatal day. Most circulating red cells w...

  8. An Herbal Galactagogue Mixture Increases Milk Production and Aquaporin Protein Expression in the Mammary Glands of Lactating Rats

    OpenAIRE

    Haibin Liu; Ying Hua; Hui Luo; Zhaojun Shen; Xuejiao Tao; Xueqiong Zhu

    2015-01-01

    Background. Herbal galactagogues have been increasingly used to treat postpartum hypogalactia. The mechanism of action of herbal galactagogues remains unclear. The purpose of this study was to investigate the effect of an herbal galactagogue mixture on milk production and aquaporin (AQP) expression in lactating rats. Methods. Thirty female Sprague Dawley rats were randomized into virgin, lactating + H2O, and lactating + galactagogue groups (n = 10 per group). Lactating rats were administered ...

  9. Regulation of the perilymphatic–endolymphatic water shunt in the cochlea by membrane translocation of aquaporin-5

    OpenAIRE

    Eckhard, A.; dos Santos, A; Liu, W; Bassiouni, M.; H. Arnold; Gleiser, C; Hirt, B; Harteneck, C; Müller, M.; Rask-Andersen, H.; Löwenheim, H

    2015-01-01

    Volume homeostasis of the cochlear endolymph depends on radial and longitudinal endolymph movements (LEMs). LEMs measured in vivo have been exclusively recognized under physiologically challenging conditions, such as experimentally induced alterations of perilymph osmolarity or endolymph volume. The regulatory mechanisms that adjust LEMs to the physiological requirements of endolymph volume homeostasis remain unknown. Here, we describe the formation of an aquaporin (AQP)-based “water shunt” d...

  10. Regulation of the perilymphatic-endolymphatic water shunt in the cochlea by membrane translocation of aquaporin-5

    OpenAIRE

    Eckhard, A.; dos Santos, A; Liu, Wei; Bassiouni, M.; H. Arnold; Gleiser, C; Hirt, B; Harteneck, C; Müller, M.; Rask-Andersen, Helge; Löwenheim, H

    2015-01-01

    Volume homeostasis of the cochlear endolymph depends on radial and longitudinal endolymph movements (LEMs). LEMs measured in vivo have been exclusively recognized under physiologically challenging conditions, such as experimentally induced alterations of perilymph osmolarity or endolymph volume. The regulatory mechanisms that adjust LEMs to the physiological requirements of endolymph volume homeostasis remain unknown. Here, we describe the formation of an aquaporin (AQP)-based “water shunt” d...

  11. Sorting of Lens Aquaporins and Connexins into Raft and Nonraft Bilayers: Role of Protein Homo-Oligomerization

    OpenAIRE

    Tong, Jihong; Briggs, Margaret M.; Mlaver, David; Vidal, Adriana; McIntosh, Thomas J.

    2009-01-01

    Two classes of channel-forming proteins in the eye lens, the water channel aquaporin-0 (AQP-0) and the connexins Cx46 and Cx50, are preferentially located in different regions of lens plasma membranes (1,2). Because these membranes contain high concentrations of cholesterol and sphingomyelin, as well as phospholipids such as phosphatidylcholine with unsaturated hydrocarbon chains, microdomains (rafts) form in these membranes. Here we test the hypothesis that sorting into lipid microdomains ca...

  12. Short-term functional adaptation of aquaporin-1 surface expression in the proximal tubule, a component of glomerulotubular balance

    OpenAIRE

    Pohl, Marcus; Shan, Qixian; Petsch, Thomas; Styp-Rekowska, Beata; Matthey, Patricia; Bleich, Markus; Bachmann, Sebastian; Theilig, Franziska

    2014-01-01

    Transepithelial water flow across the renal proximal tubule is mediated predominantly by aquaporin-1 (AQP1). Along this nephron segment, luminal delivery and transepithelial reabsorption are directly coupled, a phenomenon called glomerulotubular balance. We hypothesized that the surface expression of AQP1 is regulated by fluid shear stress, contributing to this effect. Consistent with this finding, we found that the abundance of AQP1 in brush border apical and basolateral membranes was augmen...

  13. Short-Term Functional Adaptation of Aquaporin-1 Surface Expression in the Proximal Tubule, a Component of Glomerulotubular Balance

    OpenAIRE

    Pohl, Marcus; Shan, Qixian; Petsch, Thomas; Styp-Rekowska, Beata; Matthey, Patricia; Bleich, Markus; Bachmann, Sebastian; Theilig, Franziska

    2014-01-01

    Transepithelial water flow across the renal proximal tubule is mediated predominantly by aquaporin-1 (AQP1). Along this nephron segment, luminal delivery and transepithelial reabsorption are directly coupled, a phenomenon called glomerulotubular balance. We hypothesized that the surface expression of AQP1 is regulated by fluid shear stress, contributing to this effect. Consistent with this finding, we found that the abundance of AQP1 in brush border apical and basolateral membranes was augmen...

  14. Gene Structures, Evolution, Classification and Expression Profiles of the Aquaporin Gene Family in Castor Bean (Ricinus communis L.)

    OpenAIRE

    Zhi Zou; Jun Gong; Qixing Huang; Yeyong Mo; Lifu Yang; Guishui Xie

    2015-01-01

    Aquaporins (AQPs) are a class of integral membrane proteins that facilitate the passive transport of water and other small solutes across biological membranes. Castor bean (Ricinus communis L., Euphobiaceae), an important non-edible oilseed crop, is widely cultivated for industrial, medicinal and cosmetic purposes. Its recently available genome provides an opportunity to analyze specific gene families. In this study, a total of 37 full-length AQP genes were identified from the castor bean gen...

  15. Effects of abiotic stimuli and the phytohormone ABA on the expression of the aquaporin gene family in maize roots

    OpenAIRE

    Zhu, Chuanfeng

    2005-01-01

    Major intrinsic proteins (MIPs) are an ancient family that were found in various bacteria, fungi, amphibians, plants and animals. They are collectively called aquaporins (AQPs) because some members were found to transport water, and others were shown to be permeable to small uncharged molecules such as glycerol, urea, ammonium, or formamide. In the crop plant maize, 34 cDNA sequences encoding putative AQPs had been previously identified. They include 13 plasma membrane intrinsi...

  16. Two putative-aquaporin genes are differentially expressed during arbuscular mycorrhizal symbiosis in Lotus japonicus

    OpenAIRE

    Giovannetti Marco; Balestrini Raffaella; Volpe Veronica; Guether Mike; Straub Daniel; Costa Alex; Ludewig Uwe; Bonfante Paola

    2012-01-01

    Abstract Background Arbuscular mycorrhizas (AM) are widespread symbioses that provide great advantages to the plant, improving its nutritional status and allowing the fungus to complete its life cycle. Nevertheless, molecular mechanisms that lead to the development of AM symbiosis are not yet fully deciphered. Here, we have focused on two putative aquaporin genes, LjNIP1 and LjXIP1, which resulted to be upregulated in a transcriptomic analysis performed on mycorrhizal roots of Lotus japonicus...

  17. A Nanoscale Interface Promoting Molecular and Functional Differentiation of Neural Cells.

    Science.gov (United States)

    Posati, Tamara; Pistone, Assunta; Saracino, Emanuela; Formaggio, Francesco; Mola, Maria Grazia; Troni, Elisabetta; Sagnella, Anna; Nocchetti, Morena; Barbalinardo, Marianna; Valle, Francesco; Bonetti, Simone; Caprini, Marco; Nicchia, Grazia Paola; Zamboni, Roberto; Muccini, Michele; Benfenati, Valentina

    2016-01-01

    Potassium channels and aquaporins expressed by astrocytes are key players in the maintenance of cerebral homeostasis and in brain pathophysiologies. One major challenge in the study of astrocyte membrane channels in vitro, is that their expression pattern does not resemble the one observed in vivo. Nanostructured interfaces represent a significant resource to control the cellular behaviour and functionalities at micro and nanoscale as well as to generate novel and more reliable models to study astrocytes in vitro. However, the potential of nanotechnologies in the manipulation of astrocytes ion channels and aquaporins has never been previously reported. Hydrotalcite-like compounds (HTlc) are layered materials with increasing potential as biocompatible nanoscale interface. Here, we evaluate the effect of the interaction of HTlc nanoparticles films with primary rat neocortical astrocytes. We show that HTlc films are biocompatible and do not promote gliotic reaction, while favouring astrocytes differentiation by induction of F-actin fibre alignment and vinculin polarization. Western Blot, Immunofluorescence and patch-clamp revealed that differentiation was accompanied by molecular and functional up-regulation of both inward rectifying potassium channel Kir 4.1 and aquaporin 4, AQP4. The reported results pave the way to engineering novel in vitro models to study astrocytes in a in vivo like condition. PMID:27503424

  18. Aquaporins in the wild: natural genetic diversity and selective pressure in the PIP gene family in five Neotropical tree species

    Directory of Open Access Journals (Sweden)

    Vendramin Giovanni G

    2010-06-01

    Full Text Available Abstract Background Tropical trees undergo severe stress through seasonal drought and flooding, and the ability of these species to respond may be a major factor in their survival in tropical ecosystems, particularly in relation to global climate change. Aquaporins are involved in the regulation of water flow and have been shown to be involved in drought response; they may therefore play a major adaptive role in these species. We describe genetic diversity in the PIP sub-family of the widespread gene family of Aquaporins in five Neotropical tree species covering four botanical families. Results PIP Aquaporin subfamily genes were isolated, and their DNA sequence polymorphisms characterised in natural populations. Sequence data were analysed with statistical tests of standard neutral equilibrium and demographic scenarios simulated to compare with the observed results. Chloroplast SSRs were also used to test demographic transitions. Most gene fragments are highly polymorphic and display signatures of balancing selection or bottlenecks; chloroplast SSR markers have significant statistics that do not conform to expectations for population bottlenecks. Although not incompatible with a purely demographic scenario, the combination of all tests tends to favour a selective interpretation of extant gene diversity. Conclusions Tropical tree PIP genes may generally undergo balancing selection, which may maintain high levels of genetic diversity at these loci. Genetic variation at PIP genes may represent a response to variable environmental conditions.

  19. Brain Basics

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    Full Text Available ... in Real Life Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video ... early brain development, and may also assist in learning and memory. ... rise to disabilities or diseases. neural circuit —A network of neurons ...

  20. Brain Basics

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    Full Text Available ... than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...

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    Full Text Available ... Research Modern research tools and techniques are giving scientists a more detailed understanding of the brain than ever before. Brain Imaging Using brain imaging technologies such as magnetic resonance imaging (MRI), which uses magnetic fields to take pictures of the brain's structure, studies ...

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    Full Text Available ... Welcome. Brain Basics provides information on how the brain works, how mental illnesses are disorders of the brain, ... highly developed area at the front of the brain that, in humans, plays a role in executive functions such as ...

  3. Distribution of autoimmune antibodies and clinical features in 54 cases with recurrent optic neuritis%复发性视神经炎54例临床特点及自身免疫抗体的分布

    Institute of Scientific and Technical Information of China (English)

    王颖云; 魏世辉; 范珂; 闫洪欣; 张译心; 戴艳丽

    2013-01-01

    目的 观察复发性视神经炎的临床特点以及自身免疫抗体(水通道蛋白4抗体和血清抗核抗体)的分布.方法 收集2010年10月至2012年4月间在解放军总医院神经眼科住院诊治的复发性视神经炎患者54例的临床资料,回顾分析其一般临床特点,统计其水通道蛋白4抗体(AQP4-Ab)(36例)和血清抗核抗体(ANAs)的阳性率,并与相关文献数据分析比较.结果 男女比例1∶2.6,发病年龄平均30.3岁;病程50d~20年,发病次数2~8次.病程中最差视力(矫正后)在0.1以下者44例,占81.5%.ANAs阳性率22.2% (12/54),AQP4-Ab阳性率27.8% (10/36);颅脑和/或脊髓核磁异常者占48.0% (24/50);脑脊液异常70.0% (16/23).结论 复发性视神经炎多发于青壮年,视力损害较重,自身免疫抗体(AQP4-Ab和ANAs)阳性率较视神经脊髓炎及复发性长节段横贯性脊髓炎略低,中枢神经系统影像检查对其诊治有重要价值.%ObJective To investigate the clinical features and seroprevalence of autoimmune antibodies (aquaporin-4 antibodies,AQP4-Ab and antinuclear antibodies,ANAs) in patients with recurrent optic neuritis (RON).Methods Fifty-four RON patients who were in-hospital in Ophthalmology Department of PLA from October 2010 to April 2012 were enrolled in the study.The general clinical features and statistic the positive rate of AQP4-Ab and ANAs were analyzed retrospectively,and the relative data in other studies were compared.Results The ratio of male to female was 1:2.6 and the average age of onset was 30.3 years old.The recurrent attacks of optic neuritis were 2 to 8 times during 50 days to 20 years.There were 44 patients (81.5%) who had ever appeared the lowest visual acuity (corrected) of <0.1 in the course of disease.The rate of seropositive ANAs was 22.2% (12/54) while 27.8% (10/36) for AQP4-Ab.The 48.0% (24/50) cases were abnormal in Brain and/or spinal cord MRI and 70.0% (16/23) in CSF.Conclusions RON is more appeared in

  4. Brain mapping

    Directory of Open Access Journals (Sweden)

    Blaž Koritnik

    2004-08-01

    Full Text Available Cartography of the brain ("brain mapping" aims to represent the complexities of the working brain in an understandable and usable way. There are four crucial steps in brain mapping: (1 acquiring data about brain structure and function, (2 transformation of data into a common reference, (3 visualization and interpretation of results, and (4 databasing and archiving. Electrophysiological and functional imaging methods provide information about function of the human brain. A prerequisite for multisubject, multidimensional and multimodal mapping is transformation of individual images to match a standard brain template. To produce brain maps, color, contours, and other visual cues are used to differentiate metabolic rates, electrical field potentials, receptor densities, and other attributes of structure or function. Databases are used to organize and archive data records. By relating the maps to cognitive functions and psychological models, brain mapping offers a prerequisite for the understanding of organizational principles of the human brain.

  5. Aquaporin-mediated long-distance polyphosphate translocation directed towards the host in arbuscular mycorrhizal symbiosis: application of virus-induced gene silencing.

    Science.gov (United States)

    Kikuchi, Yusuke; Hijikata, Nowaki; Ohtomo, Ryo; Handa, Yoshihiro; Kawaguchi, Masayoshi; Saito, Katsuharu; Masuta, Chikara; Ezawa, Tatsuhiro

    2016-09-01

    Arbuscular mycorrhizal fungi translocate polyphosphate through hyphae over a long distance to deliver to the host. More than three decades ago, suppression of host transpiration was found to decelerate phosphate delivery of the fungal symbiont, leading us to hypothesize that transpiration provides a primary driving force for polyphosphate translocation, probably via creating hyphal water flow in which fungal aquaporin(s) may be involved. The impact of transpiration suppression on polyphosphate translocation through hyphae of Rhizophagus clarus was evaluated. An aquaporin gene expressed in intraradical mycelia was characterized and knocked down by virus-induced gene silencing to investigate the involvement of the gene in polyphosphate translocation. Rhizophagus clarus aquaporin 3 (RcAQP3) that was most highly expressed in intraradical mycelia encodes an aquaglyceroporin responsible for water transport across the plasma membrane. Knockdown of RcAQP3 as well as the suppression of host transpiration decelerated polyphosphate translocation in proportion to the levels of knockdown and suppression, respectively. These results provide the first insight into the mechanism underlying long-distance polyphosphate translocation in mycorrhizal associations at the molecular level, in which host transpiration and the fungal aquaporin play key roles. A hypothetical model of the translocation is proposed for further elucidation of the mechanism. PMID:27136716

  6. Expression of Fragaria vesca PIP aquaporins in response to drought stress: PIP down-regulation correlates with the decline in substrate moisture content.

    Science.gov (United States)

    Šurbanovski, Nada; Sargent, Daniel J; Else, Mark A; Simpson, David W; Zhang, Hanma; Grant, Olga M

    2013-01-01

    PIP aquaporin responses to drought stress can vary considerably depending on the isoform, tissue, species or level of stress; however, a general down-regulation of these genes is thought to help reduce water loss and prevent backflow of water to the drying soil. It has been suggested therefore, that it may be necessary for the plant to limit aquaporin production during drought stress, but it is unknown whether aquaporin down-regulation is gradual or triggered by a particular intensity of the stress. In this study, ten Fragaria PIP genes were identified from the woodland strawberry (Fragaria vesca L.) genome sequence and characterised at the sequence level. The water relations of F. vesca were investigated and the effect of different intensities of drought stress on the expression of four PIP genes, as well as how drought stress influences their diurnal transcription was determined. PIP down-regulation in the root corresponded to the level of drought stress. Moreover, transcript abundance of two genes highly expressed in the root (FvPIP1;1 and FvPIP2;1) was strongly correlated to the decline in substrate moisture content. The amplitude of diurnal aquaporin expression in the leaves was down-regulated by drought without altering the pattern, but showing an intensity-dependent effect. The results show that transcription of PIP aquaporins can be fine-tuned with the environment in response to declining water availability. PMID:24086403

  7. Bilateral optic neuritis in a boy - More than the eyes.

    Science.gov (United States)

    Loh, M A; Alex Khoo, P C; Chong, M F

    2016-04-01

    Neuromyelitis optica (NMO) is a rare disorder in children with variable presentation. We report a 7-year-old boy who presented with bilateral retrobulbar optic neuritis and responded very well to treatment. He was also positive for aquaporin 4 (AQP4) antibodies, which is part of an emerging endophenotype within autoimmune neurological disorders in childhood. PMID:27326949

  8. A systematic analysis of the complement pathways in patients with neuromyelitis optica indicates alteration but no activation during remission

    DEFF Research Database (Denmark)

    Veszeli, Nóra; Füst, György; Csuka, Dorottya;

    2014-01-01

    Neuromyelitis optica (NMO) is an autoimmune demyelinating inflammatory disorder, mediated by pathogenic autoantibodies against aquaporin 4 (AQP4), the main water channel of the central nervous system (CNS). NMO is characterized by local IgG deposition and complement activation within the CNS, but...

  9. Light-mediated K(leaf) induction and contribution of both the PIP1s and PIP2s aquaporins in five tree species: walnut (Juglans regia) case study.

    Science.gov (United States)

    Baaziz, Khaoula Ben; Lopez, David; Rabot, Amelie; Combes, Didier; Gousset, Aurelie; Bouzid, Sadok; Cochard, Herve; Sakr, Soulaiman; Venisse, Jean-Stephane

    2012-04-01

    Understanding the response of leaf hydraulic conductance (K(leaf)) to light is a challenge in elucidating plant-water relationships. Recent data have shown that the effect of light on K(leaf) is not systematically related to aquaporin regulation, leading to conflicting conclusions. Here we investigated the relationship between light, K(leaf), and aquaporin transcript levels in five tree species (Juglans regia L., Fagus sylvatica L., Quercus robur L., Salix alba L. and Populus tremula L.) grown in the same environmental conditions, but differing in their K(leaf) responses to light. Moreover, the K(leaf) was measured by two independent methods (high-pressure flow metre (HPFM) and evaporative flux method (EFM)) in the most (J. regia) and least (S. alba) responsive species and the transcript levels of aquaporins were analyzed in perfused and unperfused leaves. Here, we found that the light-induced K(leaf) value was closely related to stronger expression of both the PIP1 and PIP2 aquaporin genes in walnut (J. regia), but to stimulation of PIP1 aquaporins alone in F. sylvatica and Q. robur. In walnut, all newly identified aquaporins were found to be upregulated in the light and downregulated in the dark, further supporting the relationship between the light-mediated induction of K(leaf) and aquaporin expression in walnut. We also demonstrated that the K(leaf) response to light was quality-dependent, K(leaf) being 60% lower in the absence of blue light. This decrease in K(leaf) was correlated with strong downregulation of three PIP2 aquaporins and of all the PIP1 aquaporins tested. These data support a relationship between light-mediated K(leaf) regulation and the abundance of aquaporin transcripts in the walnut tree. PMID:22544048

  10. Synthesis of robust and high-performance aquaporin-based biomimetic membranes by interfacial polymerization-membrane preparation and RO performance characterization

    DEFF Research Database (Denmark)

    Zhao, Yang; Qiu, Changquan; Li, Xuesong;

    2012-01-01

    Aquaporins are water channel proteins with excellent water permeability and solute rejection, which makes them promising for preparing high-performance biomimetic membranes. Despite the growing interest in aquaporin-based biomimetic membranes (ABMs), it is challenging to produce robust and defect...... or with inactive (mutant) aquaporins, were also similarly prepared. The separation performance of these membranes was evaluated by cross-flow reverse osmosis (RO) tests. Compared to the controls, the active ABM achieved significantly higher water permeability (∼4L/m2hbar) with comparable NaCl rejection (∼97......%) at an applied pressure of 5bar. Its permeability was ∼40% higher compared to a commercial brackish water RO membrane (BW30) and an order of magnitude higher compared to a seawater RO membrane (SW30HR), which clearly demonstrates the great potential of the TFC ABM for desalination applications....

  11. Brain Basics

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    Full Text Available ... Trials — Participants Statistics Help for Mental Illnesses Outreach Research Priorities Funding Labs at NIMH News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The ...

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  8. Brain Diseases

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  9. Brain Basics

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    Full Text Available ... of brain scan called magnetoencephalography, or MEG, can capture split-second changes in the brain. Using MEG, ... The study of how environmental factors like diet, stress and post-natal care can change gene expression ( ...

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  3. Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

    Directory of Open Access Journals (Sweden)

    Kiminori Sada

    Full Text Available We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs, cellular hypoxia increased after incubation with high glucose (HG. A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1, a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

  4. Aquaporin-9 immunohistochemistry in varicocele testes as a consequence of hypoxia in the sperm production site.

    Science.gov (United States)

    Arena, S; Arena, F; Maisano, D; Di Benedetto, V; Romeo, C; Nicòtina, P A

    2011-02-01

    Aquaporin-9 (AQP-9) regulates tissue hydration by promoting transmembrane exchanges of both water and solutes, such as lactate. The latter is a key metabolite of primary spermatocytes and of maturing haploid germ cells (h-GCs). The present investigation was aimed at immunolocalising human AQP-9 in both normal and varicocele testes. Histology and immmunocytochemistry were investigated in archival biopsies from 20 varicocele testes and in eight unaffected ones. AQP-9 immunostaining was performed using a rabbit antibody, and either focal or diffuse cell membrane labelling was recorded. Varicocele testes showed disarranged tubular compartments, with sloughing h-GCs, tissue hyperhydration, spermiogenesis failure and fibrosis. AQP-9 immunohistology of the control testes showed a diffuse cell membrane staining of the primary spermatocytes and h-GCs, without any positive reaction of spermatogonia and Sertoli cells. AQP-9 cell expression in the varicocele testes was focal or lacking in both adluminal and sloughing GCs. AQP-9 expression occurs in normal human testis, at cell membrane of primary spermatocytes and h-GCs, suggesting a possible role of AQP-9 in the water and lactate transport from Sertoli cells to GCs. AQP-9 is focal or lacking in adolescent varicocele testes, and this suggests AQP-9 to be downregulated in such testicular disorder, leading to lactate deprivation with subsequent hypospermatogenesis. PMID:21219380

  5. Overexpression of the wheat aquaporin gene, TaAQP7, enhances drought tolerance in transgenic tobacco.

    Science.gov (United States)

    Zhou, Shiyi; Hu, Wei; Deng, Xiaomin; Ma, Zhanbing; Chen, Lihong; Huang, Chao; Wang, Chen; Wang, Jie; He, Yanzhen; Yang, Guangxiao; He, Guangyuan

    2012-01-01

    Aquaporin (AQP) proteins have been shown to transport water and other small molecules through biological membranes, which is crucial for plants to combat stress caused by drought. However, the precise role of AQPs in drought stress response is not completely understood in plants. In this study, a PIP2 subgroup gene AQP, designated as TaAQP7, was cloned and characterized from wheat. Expression of TaAQP7-GFP fusion protein revealed its localization in the plasma membrane. TaAQP7 exhibited high water channel activity in Xenopus laevis oocytes and TaAQP7 transcript was induced by dehydration, and treatments with polyethylene glycol (PEG), abscisic acid (ABA) and H(2)O(2). Further, TaAQP7 was upregulated after PEG treatment and was blocked by inhibitors of ABA biosynthesis, implying that ABA signaling was involved in the upregulation of TaAQP7 after PEG treatment. Overexpression of TaAQP7 increased drought tolerance in tobacco. The transgenic tobacco lines had lower levels of malondialdehyde (MDA) and H(2)O(2), and less ion leakage (IL), but higher relative water content (RWC) and superoxide dismutase (SOD) and catalase (CAT) activities when compared with the wild type (WT) under drought stress. Taken together, our results show that TaAQP7 confers drought stress tolerance in transgenic tobacco by increasing the ability to retain water, reduce ROS accumulation and membrane damage, and enhance the activities of antioxidants. PMID:23285044

  6. Aquaporin-3 potentiates allergic airway inflammation in ovalbumin-induced murine asthma

    Science.gov (United States)

    Ikezoe, Kohei; Oga, Toru; Honda, Tetsuya; Hara-Chikuma, Mariko; Ma, Xiaojun; Tsuruyama, Tatsuaki; Uno, Kazuko; Fuchikami, Jun-ichi; Tanizawa, Kiminobu; Handa, Tomohiro; Taguchi, Yoshio; Verkman, Alan S.; Narumiya, Shuh; Mishima, Michiaki; Chin, Kazuo

    2016-01-01

    Oxidative stress plays a pivotal role in the pathogenesis of asthma. Aquaporin-3 (AQP3) is a small transmembrane water/glycerol channel that may facilitate the membrane uptake of hydrogen peroxide (H2O2). Here we report that AQP3 potentiates ovalbumin (OVA)-induced murine asthma by mediating both chemokine production from alveolar macrophages and T cell trafficking. AQP3 deficient (AQP3−/−) mice exhibited significantly reduced airway inflammation compared to wild-type mice. Adoptive transfer experiments showed reduced airway eosinophilic inflammation in mice receiving OVA-sensitized splenocytes from AQP3−/− mice compared with wild-type mice after OVA challenge, consistently with fewer CD4+ T cells from AQP3−/− mice migrating to the lung than from wild-type mice. Additionally, in vivo and vitro experiments indicated that AQP3 induced the production of some chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized alveolar macrophages. These results imply a critical role of AQP3 in asthma, and AQP3 may be a novel therapeutic target. PMID:27165276

  7. Expression, localization and possible functions of aquaporins 3 and 8 in rat digestive system.

    Science.gov (United States)

    Zhao, G X; Dong, P P; Peng, R; Li, J; Zhang, D Y; Wang, J Y; Shen, X Z; Dong, L; Sun, J Y

    2016-01-01

    Although aquaporins (AQPs) play important roles in transcellular water movement, their precise quantification and localization remains controversial. We investigated expression levels and localizations of AQP3 and AQP8 and their possible functions in the rat digestive system using real-time polymerase chain reactions, western blot analysis and immunohistochemistry. We investigated the expression levels and localizations of AQP3 and AQP8 in esophagus, forestomach, glandular stomach, duodenum, jejunum, ileum, proximal and distal colon, and liver. AQP3 was expressed in the basolateral membranes of stratified epithelia (esophagus and forestomach) and simple columnar epithelia (glandular stomach, ileum, and proximal and distal colon). Expression was particularly abundant in the esophagus, and proximal and distal colon. AQP8 was found in the subapical compartment of columnar epithelial cells of the jejunum, ileum, proximal colon and liver; the most intense staining occurred in the jejunum. Our results suggest that AQP3 and AQP8 play significant roles in intestinal function and/or fluid homeostasis and may be an important subject for future investigation of disorders that involve disruption of intestinal fluid homeostasis, such as inflammatory bowel disease and irritable bowel syndrome. PMID:26983346

  8. Two isoforms of aquaporin 2 responsive to hypertonic stress in the bottlenose dolphin.

    Science.gov (United States)

    Suzuki, Miwa; Wakui, Hitomi; Itou, Takuya; Segawa, Takao; Inoshima, Yasuo; Maeda, Ken; Kikuchi, Kiyoshi

    2016-04-15

    This study investigated the expression of aquaporin 2 (AQP2) and its newly found alternatively spliced isoform (alternative AQP2) and the functions of these AQP2 isoforms in the cellular hyperosmotic tolerance in the bottlenose dolphin, ITALIC! Tursiops truncatus mRNA sequencing revealed that alternative AQP2 lacks the fourth exon and instead has a longer third exon that includes a part of the original third intron. The portion of the third intron, now part of the coding region of alternative AQP2, is highly conserved among many species of the order Cetacea but not among terrestrial mammals. Semi-quantitative PCR revealed that AQP2 was expressed only in the kidney, similar to terrestrial mammals. In contrast, alternative AQP2 was expressed in all organs examined, with strong expression in the kidney. In cultured renal cells, expression of both AQP2 isoforms was upregulated by the addition to the medium of NaCl but not by the addition of mannitol, indicating that the expression of both isoforms is induced by hypersalinity. Treatment with small interfering RNA for both isoforms resulted in a decrease in cell viability in hypertonic medium (500 mOsm kg(-1)) when compared with controls. These findings indicate that the expression of alternatively spliced AQP2 is ubiquitous in cetacean species, and it may be one of the molecules important for cellular osmotic tolerance throughout the body. PMID:26944501

  9. Red blood cell aquaporin-1 expression is decreased in hereditary spherocytosis.

    Science.gov (United States)

    Crisp, Renée L; Maltaneri, Romina E; Vittori, Daniela C; Solari, Liliana; Gammella, Daniel; Schvartzman, Gabriel; García, Eliana; Rapetti, María C; Donato, Hugo; Nesse, Alcira

    2016-10-01

    Aquaporin-1 (AQP1) is the membrane water channel responsible for changes in erythrocyte volume in response to the tonicity of the medium. As the aberrant distribution of proteins in hereditary spherocytosis (HS) generates deficiencies of proteins other than those codified by the mutated gene, we postulated that AQP1 expression might be impaired in spherocytes. AQP1 expression was evaluated through flow cytometry in 5 normal controls, 1 autoimmune hemolytic anemia, 10 HS (2 mild, 3 moderate, 2 severe, and 3 splenectomized), and 3 silent carriers. The effect of AQP1 inhibitors was evaluated through water flow-based tests: osmotic fragility and hypertonic cryohemolysis. Serum osmolality was measured in 20 normal controls and 13 HS. The effect of erythropoietin (Epo) on AQP1 expression was determined in cultures of erythroleukemia UT-7 cells, dependent on Epo to survive. Independent of erythrocyte size, HS patients showed a lower content of AQP1 in erythrocyte membranes which correlated with the severity of the disease. Accordingly, red blood cells from HS subjects were less sensitive to cryohemolysis than normal erythrocytes after inhibition of the AQP1 water channel. A lower serum osmolality in HS with respect to normal controls suggests alterations during reticulocyte remodeling. The decreased AQP1 expression could contribute to explain variable degrees of anemia in hereditary spherocytosis. The finding of AQP1 expression induced by Epo in a model of erythroid cells may be interpreted as a mechanism to restore the balance of red cell water fluxes. PMID:27465156

  10. Unexpected complexity of the Aquaporin gene family in the moss Physcomitrella patens

    Directory of Open Access Journals (Sweden)

    Johanson Urban

    2008-04-01

    Full Text Available Abstract Background Aquaporins, also called major intrinsic proteins (MIPs, constitute an ancient superfamily of channel proteins that facilitate the transport of water and small solutes across cell membranes. MIPs are found in almost all living organisms and are particularly abundant in plants where they form a divergent group of proteins able to transport a wide selection of substrates. Results Analyses of the whole genome of Physcomitrella patens resulted in the identification of 23 MIPs, belonging to seven different subfamilies, of which only five have been previously described. Of the newly discovered subfamilies one was only identified in P. patens (Hybrid Intrinsic Protein, HIP whereas the other was found to be present in a wide variety of dicotyledonous plants and forms a major previously unrecognized MIP subfamily (X Intrinsic Proteins, XIPs. Surprisingly also some specific groups within subfamilies present in Arabidopsis thaliana and Zea mays could be identified in P. patens. Conclusion Our results suggest an early diversification of MIPs resulting in a large number of subfamilies already in primitive terrestrial plants. During the evolution of higher plants some of these subfamilies were subsequently lost while the remaining subfamilies expanded and in some cases diversified, resulting in the formation of more specialized groups within these subfamilies.

  11. Relationship between hexokinase and the aquaporin PIP1 in the regulation of photosynthesis and plant growth.

    Directory of Open Access Journals (Sweden)

    Gilor Kelly

    Full Text Available Increased expression of the aquaporin NtAQP1, which is known to function as a plasmalemma channel for CO₂ and water, increases the rate of both photosynthesis and transpiration. In contrast, increased expression of Arabidopsis hexokinase1 (AtHXK1, a dual-function enzyme that mediates sugar sensing, decreases the expression of photosynthetic genes and the rate of transpiration and inhibits growth. Here, we show that AtHXK1 also decreases root and stem hydraulic conductivity and leaf mesophyll CO₂ conductance (g(m. Due to their opposite effects on plant development and physiology, we examined the relationship between NtAQP1 and AtHXK1 at the whole-plant level using transgenic tomato plants expressing both genes simultaneously. NtAQP1 significantly improved growth and increased the transpiration rates of AtHXK1-expressing plants. Reciprocal grafting experiments indicated that this complementation occurs when both genes are expressed simultaneously in the shoot. Yet, NtAQP1 had only a marginal effect on the hydraulic conductivity of the double-transgenic plants, suggesting that the complementary effect of NtAQP1 is unrelated to shoot water transport. Rather, NtAQP1 significantly increased leaf mesophyll CO₂ conductance and enhanced the rate of photosynthesis, suggesting that NtAQP1 facilitated the growth of the double-transgenic plants by enhancing mesophyll conductance of CO₂.

  12. Overexpression of the wheat aquaporin gene, TaAQP7, enhances drought tolerance in transgenic tobacco.

    Directory of Open Access Journals (Sweden)

    Shiyi Zhou

    Full Text Available Aquaporin (AQP proteins have been shown to transport water and other small molecules through biological membranes, which is crucial for plants to combat stress caused by drought. However, the precise role of AQPs in drought stress response is not completely understood in plants. In this study, a PIP2 subgroup gene AQP, designated as TaAQP7, was cloned and characterized from wheat. Expression of TaAQP7-GFP fusion protein revealed its localization in the plasma membrane. TaAQP7 exhibited high water channel activity in Xenopus laevis oocytes and TaAQP7 transcript was induced by dehydration, and treatments with polyethylene glycol (PEG, abscisic acid (ABA and H(2O(2. Further, TaAQP7 was upregulated after PEG treatment and was blocked by inhibitors of ABA biosynthesis, implying that ABA signaling was involved in the upregulation of TaAQP7 after PEG treatment. Overexpression of TaAQP7 increased drought tolerance in tobacco. The transgenic tobacco lines had lower levels of malondialdehyde (MDA and H(2O(2, and less ion leakage (IL, but higher relative water content (RWC and superoxide dismutase (SOD and catalase (CAT activities when compared with the wild type (WT under drought stress. Taken together, our results show that TaAQP7 confers drought stress tolerance in transgenic tobacco by increasing the ability to retain water, reduce ROS accumulation and membrane damage, and enhance the activities of antioxidants.

  13. Regulatory Effect of Dexamethasone on Aquaporin-1 Expression in Cultured Bovine Trabecular Meshwork Cells

    Institute of Scientific and Technical Information of China (English)

    XIONG Xinchun; MIAO Juan; XI Zulian; ZHANG Haijiang; HAN Bo; HU Yizhen

    2005-01-01

    To evaluate the effect of dexamethasone on the expression of aquaporin-1 (AQP-1) in cultured bovine trabecular meshwork cells, bovine trabecular meshwork cells were cultured in vitro and reproduced to the third and the fourth generation, then treated with dexamethasone at the concentrations of 5, 25, 50, 250 μg/L respectively for 7 days. Immunohistochemical technique-supervision method was employed to measure, and image analysis system to analyze the expression of AQP-1 in normal cultured bovine trabecular meshwork cells and those treated with dexamethasone.In normal bovine trabecular meshwork cells, the grayscale of AQP-1 positive staining was 167.94±1.18, while it was 168.92±0.91, 176.72±1.80, 180.64±1.31, 185.64±1.58 in cells treated with 5, 25, 50, 250 tg/L concentrations of dexamethasone. When the concentration of dexamethasone was higher than 25 μg/L, the expression of AQP-1 was significantly inhibited (P<0.05).The regulation of AQP-1 expression by dexamethasone in cultured bovine trabecular meshwork cells in vitro may be one of causes that retard the aqueous outflow in glucocorticoid induced glaucoma.

  14. Cloning, identification, and bioinformatics analysis of a putative aquaporin TsAQP from Trichinella spiralis.

    Science.gov (United States)

    Cui, J M; Zhang, N Z; Li, W H; Yan, H B; Fu, B Q

    2015-01-01

    Vaccination as a preventative strategy against Trichinella spiralis infection is an ongoing effort, although no ideal vaccine candidates have been identified until now. Identification of more effective antigens that have a role in essential life stages of the parasite and that may be effective vaccine candidates is therefore of importance. In the present study, we identified a novel aquaporin gene (TsAQP) from T. spiralis, and the potential antigenicity of TsAQP was evaluated by epitope prediction. A total of 11 post-translational modification sites were predicted in the protein and fell into 4 categories: N-glycosylation; casein kinase II phosphorylation; protein kinase C phosphorylation; and N-myristoylation sites. TsAQP is a membrane intrinsic protein with high hydrophobicity; the main hydrophobic domains comprised up to 38.5% of the protein and were distributed at amino acid positions 21-43, 54-71, 83-91, 107-121, 163-174, 187-200, and 242-261. The protein consisted mainly of helices (39.58%) and loops (50%). The advanced structure of TsAQP was predicted using homology modeling, which showed that the protein was formed from 6 membrane-spanning domains connected by 5 loops. Based on these analyses, 6 potential B-cell epitopes and 4 potential T-cell epitopes were further predicted. These results suggest that TsAQP could be a promising antigen candidate for vaccination against T. spiralis. PMID:26505421

  15. Aquaporin 5 distribution pattern during development of the mouse sublingual salivary gland.

    Science.gov (United States)

    Aure, Marit H; Larsen, Helga S; Ruus, Ann-Kristin; Galtung, Hilde K

    2011-10-01

    Aquaporin 5 (AQP5) is important in salivary fluid secretion, and has been found in acinar cells of salivary glands in several species. Recently, studies have shown the AQP5 transcript and protein expression patterns as well as the temporal-spatial protein distribution during development of the mouse submandibular salivary gland. The AQP5 distribution pattern of the closely located sublingual gland (SLG) is, however, not well known. Thus, in this study, the Aqp5 RNA expression pattern and the temporal-spatial distribution of AQP5 protein in prenatal development and in adult mouse SLG was investigated. SLGs from embryonic day 14.5 (E14.5) to 18.5 and postnatal days 0 (P0), 25, and 60 were examined using real time PCR and immunohistochemistry. The Aqp5 transcript was detected from E13.5 and was found to increase towards birth and in young adults. The protein was first detected in a scattered pattern in the canalicular stage and became more organized in the luminal membrane of the acinar cells towards birth. During all postnatal developmental stages studied, AQP5 was localized in the luminal and lateral membrane of acinar cells. AQP5 was also detected in the intercalated duct and additional apical membrane staining in the entire intralobular duct was found in the terminal bud stage. These results indicate that AQP5 plays a role during embryonic salivary gland development. PMID:21818558

  16. Aquaporin-3 potentiates allergic airway inflammation in ovalbumin-induced murine asthma.

    Science.gov (United States)

    Ikezoe, Kohei; Oga, Toru; Honda, Tetsuya; Hara-Chikuma, Mariko; Ma, Xiaojun; Tsuruyama, Tatsuaki; Uno, Kazuko; Fuchikami, Jun-Ichi; Tanizawa, Kiminobu; Handa, Tomohiro; Taguchi, Yoshio; Verkman, Alan S; Narumiya, Shuh; Mishima, Michiaki; Chin, Kazuo

    2016-01-01

    Oxidative stress plays a pivotal role in the pathogenesis of asthma. Aquaporin-3 (AQP3) is a small transmembrane water/glycerol channel that may facilitate the membrane uptake of hydrogen peroxide (H2O2). Here we report that AQP3 potentiates ovalbumin (OVA)-induced murine asthma by mediating both chemokine production from alveolar macrophages and T cell trafficking. AQP3 deficient (AQP3(-/-)) mice exhibited significantly reduced airway inflammation compared to wild-type mice. Adoptive transfer experiments showed reduced airway eosinophilic inflammation in mice receiving OVA-sensitized splenocytes from AQP3(-/-) mice compared with wild-type mice after OVA challenge, consistently with fewer CD4(+) T cells from AQP3(-/-) mice migrating to the lung than from wild-type mice. Additionally, in vivo and vitro experiments indicated that AQP3 induced the production of some chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized alveolar macrophages. These results imply a critical role of AQP3 in asthma, and AQP3 may be a novel therapeutic target. PMID:27165276

  17. Dexamethasone increases aquaporin-2 protein expression in ex vivo inner medullary collecting duct suspensions.

    Science.gov (United States)

    Chen, Minguang; Cai, Hui; Klein, Janet D; Laur, Oskar; Chen, Guangping

    2015-01-01

    Aquaporin-2 (AQP2) is the vasopressin-regulated water channel that controls renal water reabsorption and plays an important role in the maintenance of body water homeostasis. Excessive glucocorticoid as often seen in Cushing's syndrome causes water retention. However, whether and how glucocorticoid regulates AQP2 remains unclear. In this study, we examined the direct effect of dexamethasone on AQP2 protein expression and activity. Dexamethasone increased AQP2 protein abundance in rat inner medullary collecting duct (IMCD) suspensions. This was confirmed in HEK293 cells transfected with AQP2 cDNA. Cell surface protein biotinylation showed an increase of dexamethasone-induced cell membrane AQP2 expression and this effect was blocked by glucocorticoid receptor antagonist RU486. Functionally, dexamethasone treatment of oocytes injected with an AQP2 cRNA increased water transport activity as judged by cell rupture time in a hypo-osmotic solution (66 ± 13 s in dexamethasone vs. 101 ± 11 s in control, n = 15). We further found that dexamethasone treatment reduced AQP2 protein degradation, which could result in an increase of AQP2 protein. Interestingly, dexamethasone promoted cell membrane AQP2 moving to less buoyant lipid raft submicrodomains. Taken together, our data demonstrate that dexamethasone promotes AQP2 protein expression and increases water permeability mainly via inhibition of AQP2 protein degradation. The increase in AQP2 activity promotes water reabsorption, which may contribute to glucocorticoid-induced water retention and hypertension. PMID:26578982

  18. Aquaporin gene therapy corrects Sjögren's syndrome phenotype in mice.

    Science.gov (United States)

    Lai, Zhennan; Yin, Hongen; Cabrera-Pérez, Javier; Guimaro, Maria C; Afione, Sandra; Michael, Drew G; Glenton, Patricia; Patel, Ankur; Swaim, William D; Zheng, Changyu; Nguyen, Cuong Q; Nyberg, Fred; Chiorini, John A

    2016-05-17

    Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease that is estimated to affect 35 million people worldwide. Currently, no effective treatments exist for Sjögren's syndrome, and there is a limited understanding of the physiological mechanisms associated with xerostomia and hyposalivation. The present work revealed that aquaporin 5 expression, a water channel critical for salivary gland fluid secretion, is regulated by bone morphogenetic protein 6. Increased expression of this cytokine is strongly associated with the most common symptom of primary Sjögren's syndrome, the loss of salivary gland function. This finding led us to develop a therapy in the treatment of Sjögren's syndrome by increasing the water permeability of the gland to restore saliva flow. Our study demonstrates that the targeted increase of gland permeability not only resulted in the restoration of secretory gland function but also resolved the hallmark salivary gland inflammation and systemic inflammation associated with disease. Secretory function also increased in the lacrimal gland, suggesting this local therapy could treat the systemic symptoms associated with primary Sjögren's syndrome. PMID:27140635

  19. Spreading of porous vesicles subjected to osmotic shocks: the role of aquaporins.

    Science.gov (United States)

    Berthaud, Alice; Quemeneur, François; Deforet, Maxime; Bassereau, Patricia; Brochard-Wyart, Françoise; Mangenot, Stéphanie

    2016-02-01

    Aquaporin 0 (AQP0) is a transmembrane protein specific to the eye lens, involved as a water carrier across the lipid membranes. During eye lens maturation, AQP0s are truncated by proteolytic cleavage. We investigate in this work the capability of truncated AQP0 to conduct water across membranes. We developed a method to accurately determine water permeability across lipid membranes and across proteins from the deflation under osmotic pressure of giant unilamellar vesicles (GUVs) deposited on an adhesive substrate. Using reflection interference contrast microscopy (RICM), we measure the spreading area of GUVs during deswelling. We interpret these results using a model based on hydrodynamic, binder diffusion towards the contact zone, and Helfrich's law for the membrane tension, which allows us to relate the spread area to the vesicle internal volume. We first study the specific adhesion of vesicles coated with biotin spreading on a streptavidin substrate. We then determine the permeability of a single functional AQP0 and demonstrate that truncated AQP0 is no more a water channel. PMID:26662491

  20. New Findings on the Mechanism of Perspiration Including Aquaporin-5 Water Channel.

    Science.gov (United States)

    Inoue, Risako

    2016-01-01

    Aquaporin-5 (AQP5) is a member of the water channel protein family. Although AQP5 has been shown to be present in sweat glands, the presence or absence of regulated intracellular translocation of AQP5 in sweat glands remains to be determined. In this article, recent findings on AQP5 in sweat glands are presented. (1) Immunoreactive AQP5 was detected in the apical membranes and the intercellular canaliculi of secretory coils, and in the basolateral membranes of the clear cells in human eccrine sweat glands. (2) AQP5 rapidly concentrated at the apical membranes during sweating in mouse sweat glands. (3) Treatment of human AQP5-expressing Madin-Darby canine kidney cells with calcium ionophore A23187 resulted in a twofold increase in the AQP5 level in the apical membranes within 5 min. (4) Anoctamin-1, a calcium-activated chloride channel was detected in the apical membranes and it completely colocalized with AQP5 in the apical membranes in mouse sweat glands. AQP5 may be involved in sweating and its translocation may help to increase the water permeability of the apical membranes of sweat glands. AQP5 is a potential target molecule for the design of a sweat-modulating drug. PMID:27584958