Role Of Aquaporins Research Articles

Prolactin Directs Branchial and Intestinal Gene Expression of Solute Transporters and Aquaporins in Mummichog (Fundulus heteroclitus)

Mummichogs (Fundulus heteroclitus) can inhabit a wide range of environmental salinities because of their capacity to modulate the expression of genes that encode solute transporters and water channels within key osmoregulatory organs. Over 60 years ago, the pituitary hormone, prolactin (Prl), was identified as an essential factor that enables mummichogs to tolerate freshwater (FW) environments; nonetheless, the molecular targets of Prl signaling in this model teleost remain unknown. In the current study, we determined that two Prl receptors, designated prlra and prlrb, are expressed in osmoregulatory organs in salinity‐dependent fashions. We administered ovine Prl (oPrl; 1 or 5 mg g‐1 body weight) by intraperitoneal injection to mummichogs held in brackish water (12 ppt) and first characterized the expression of genes associated with FW‐type (ion absorptive) and seawater (SW)‐type (ion secretory) ionocytes. Within FW‐type ionocytes, oPrl stimulated the expression of Na+/Cl‐ cotransporter 2, aquaporin 3, and prlra. Branchial Na+/H+ exchanger 2and ‐3 gene expression did not respond to oPrl. The expression levels of genes associated with SW‐type ionocytes, such as Na+/K+/2Cl‐cotransporter 1and cystic fibrosis transmembrane regulator 1, were reduced following oPrl administration. Given the role of aquaporins in supporting fluid absorption by the intestine, we then assessed whether multiple aquaporin encoding genes were responsive to oPrl. We observed that aquaporin 1a and ‐8 were diminished by oPrl. As in the gill, oPrl stimulated the expression of prlra. Our collective data indicate that Prl promotes the survival of mummichogs in FW by simultaneously modulating a suite of genes within the gill and intestine that underlie critical ion‐ and water‐transporting processes.

Aquaporin-based membranes made by interfacial polymerization in hollow fibers: Visualization and role of aquaporin in water permeability

Aquaporins are water channel proteins with high permeability and solute rejection, making them ideal components for the preparation of desalination biomimetic membranes. In one strategy, E. coli aquaporin Z (AqpZ) proteoliposomes are immobilized in a polyamide layer formed by interfacial polymerization at the inner surface of hollow fibers. However, once polymerization occurs, the system is almost a black box where it is difficult to disentangle the relative contribution to performance of (i) water permeation through AqpZ channels and (ii) the possible modification of the properties or structure of the polymer layer by the mere presence of protein and lipid. Indeed, the fate of protein and lipid once the polymer is formed, and how much of it is actually used, is under debate. Also, the performance of these modules has been reported to be stable over several months. This is intriguing because of the expected degradation of functional AqpZ and lipid with time. Herein, we used lipid and AqpZ, both fluorescently labeled, to unequivocally localize both components only at the inner surface of the hollow fibers. To characterize module performance, we tested about 30 half-inch modules containing five hollow fibers each. Those reconstituted with wild type AqpZ produced higher permeability (∼8.5 ± 0.9 LMH/bar) than those reconstituted with AqpZ mutant (R189A) (∼5.6 ± 1.7 LMH/bar) or lipid-only liposomes (3.7 ± 1.1 LMH/bar). However, while these differences are significant, they are smaller than expected from the comparison of relative permeabilities of membranes incorporating wild-type AqpZ, R189A mutant and only-lipid. In addition, we show that in a five-month long experiment, performance of two of these modules showed only minor deterioration, if any, which is not consistent with the observed rapid degradation of proteoliposomes at room temperature. Overall, these data obtained in this set-up suggests that although both AqpZ and lipid are localized at the inner of the hollow fibers, they mainly behave as additives that modify the properties of the robust polyamide layer. A small contribution of AqpZ channel activity to module performance is possible, but to be significant it would require full coverage and a higher protein density in the proteoliposomes, which at present cannot be achieved in the current protocol.

Aquaporin 9 regulates Leydig cell steroidogenesis in diabetes

Diabetes mellitus induced hyperglycemia increases oxidative stress, which contributes to impairment of male reproductive function. Aquaporins (AQPs) belong to a transmembrane protein superfamily containing 13 isoforms (AQP0-12), differentially expressed in various organs, and play a pivotal role in male reproductive function. In the current study, we investigated the relationship between AQPs and testicular steroidogenesis under hyperglycemia in vivo and in vitro. The effect of high glucose on the role of AQPs in Leydig cell steroidogenesis was analyzed in diabetic rats (in-vivo) and LC540 rat Leydig cells (in vitro) via enzyme assays, quantitative RT-PCR, siRNA knock down and western blotting. AQP 9 was significantly up-regulated in STZ-induced diabetic rat testis and high glucose treated LC540 cells. Further, oxidative stress marker nuclear factor erythroid 2-related factor 2 (Nrf2) expression was decreased with impaired testicular steroidogenesis under hyperglycemia. Knock-down of AQP 9 resulted in increased Nrf2 expression and thus increased testicular steroidogenesis in hyperglycemia. Diabetes-associated hyperglycemia induced oxidative stress is a widely proven cause for diabetes-related male infertility. Our results collectively suggest that AQP 9 impairs testicular steroidogenesis via the regulation of oxidative stress in diabetes.

The Role of Aquaporin 7 in the Movement of Water and Cryoprotectants in Bovine In Vitro Matured Oocytes.

Simple SummaryThe permeability of the plasma membrane to water and cryoprotectants is a critical factor in the effective vitrification of oocytes. The goal of this study is to better understand the pathways used to transport water and other cryoprotectants through the plasma membrane of bovine in vitro matured oocytes, with a focus on the role of aquaporin 7 (AQP7). We demonstrated that cryoprotectants stimulated AQP3 and AQP7 but not AQP9 expression in mature bovine oocytes. Dimethyl sulfoxide upregulates AQP3 expression, while ethylene glycol upregulates AQP7 expression in oocytes in a CPA-dependent fashion. We also demonstrated that exogenous expression of aquaglyceroporins such as AQP7 is possible in in vitro matured oocytes. When permeability values for membrane transport of dimethyl sulfoxide, ethylene glycol and sucrose were assessed, we observed that AQP7 overexpressed oocytes are more permeable to water in the presence of dimethyl sulfoxide solution. These biophysical characteristics, together with the use of membrane transport modeling, will allow re-evaluation and possibly improvement of previously described protocols for bovine oocyte cryopreservation.Aquaglyceroporins are known as channel proteins, and are able to transport water and small neutral solutes. In this study, we evaluate the effect of exposure of in vitro matured bovine oocytes to hyperosmotic solutions containing ethylene glycol (EG), dimethyl sulfoxide (Me2SO) or sucrose on the expression levels of AQP3, AQP7 and AQP9. Moreover, we studied whether artificial protein expression of AQP7 in bovine oocytes increases their permeability to water and cryoprotectants. Exposure to hyperosmotic solutions stimulated AQP3 and AQP7 but not AQP9 expression. Oocytes exposed to hyperosmotic Me2SO solution exhibited upregulated AQP3 expression, while AQP7 expression was upregulated by EG hyperosmotic exposure. Microinjection of oocytes at the germinal vesicle stage with enhanced green fluorescent protein (EGFP) or EGFP+AQP7 cRNAs resulted in the expression of the corresponding proteins in ≈86% of the metaphase-II stage oocytes. AQP7 facilitated water diffusion when bovine MII oocytes were in presence of Me2SO solution but not EG or sucrose solution. However, the overexpression of this aquaporin did not increase membrane permeability to Me2SO or EG. In summary, cryoprotectant-induced increase of AQP3 and AQP7 expression could be one of the mechanisms underlying oocyte tolerance to hyperosmotic stress. Water diffusion appears to be improved when AQP7 overexpressed oocytes are exposed to Me2SO, shortening the time required for oocytes to achieve osmotic balance with cryoprotectant solutions.

Apoptotic changes and aquaporin-1 expression in the choroid plexus of cerebral malaria patients

BackgroundCerebral malaria (CM) is associated with sequestration of parasitized red blood cells (PRBCs) in the capillaries. Often, the association of CM with cerebral oedema is related with high mortality rate. Morphological changes of the choroid plexus (CP) and caspase-3 expression in CM have not been reported. In addition, limited knowledge is known regarding the role of aquaporin (AQP)-1 in CM. The present study evaluated changes in the CP, explored apoptotic changes and AQP-1 expression in CP epithelial cells (CPECs) in fatal CM patients.MethodsCP from fatal Plasmodium falciparum malaria patients (5 non-CM [NCM], 16 CM) were retrieved and prepared for histopathological evaluation. Caspase-3 and AQP-1 expressions in CPECs were investigated by immunohistochemistry.ResultsHistologically, apoptotic changes in CPECs were significantly observed in the CM group compared with the NCM and normal control (NC) groups (p < 0.05). These changes included cytoplasmic and nuclear condensation/shrinkage of CPECs and detachment of CPECs from the basement membrane. The apoptotic changes were positively correlated with caspase-3 expression in the nuclei of CPECs. In addition, AQP-1 expression in CPECs was significantly decreased in the CM group compared with the NCM and NC groups (all p < 0.001). A negative correlation (rs = − 0.450, p = 0.024) was documented between caspase-3 expression in the nuclei of CPECs and AQP-1.ConclusionsApoptotic changes and altered AQP-1 expression may contribute to CPEC dysfunction and subsequently reduce cerebrospinal fluid production, affecting the water homeostasis in the brains of patients with CM.

Aquaporins in Pacific White Shrimp (Litopenaeus vannamei): Molecular Characterization, Expression Patterns, and Transcriptome Analysis in Response to Salinity Stress

Aquaporins (AQPs) are integral membrane proteins that facilitate the transport of water and small solutes across cell membranes. These proteins are vital for maintaining water homeostasis in living organisms. In mammals, thirteen aquaporins have been characterized, but in crustaceans, especially penaeid shrimp, the diversity, structure, and substrate specificity of these membrane channel proteins are largely unknown. We here presented the three types of AQPs from Litopenaeus vannamei based on genome and transcriptome sequencing. Phylogenetic analysis showed that each AQP separately represented members of aquaglyceroporins, classical aquaporins, and unorthodox aquaporins, thus they were named as LvAQP3, LvAQP4, and LvAQP11. The LvAqp4 was mostly expressed in hepatopancreas, stomach, and gill, meanwhile LvAqp3 and LvAqp11 were separately predominantly expressed in intestine and muscle, respectively. To investigate possible roles of aquaporins in osmoregulation, mRNA expression changes in mainly expressed tissues were analyzed after acute exposure or long-term acclimation to different salinities. The results revealed that the expression levels of aquaporins genes were significantly decreased in most tissues (except hepatopancreas) under salinity stress, though the expression patterns were variable among isoforms and tissues. Moreover, comparative transcriptome analysis indicated the combination roles of aquaglyceroporin and amino acid metabolism related genes and pathways in response to acute salinity changes in the intestine. This study opened new windows for future investigations and provided new insights into the role of aquaporins in osmoregulation in L. vannamei.

Aquaporin-4 deletion attenuates opioid-induced addictive behaviours associated with dopamine levels in nucleus accumbens

There is a lack of safe and effective non-opioid medications for the treatment of opioid addiction. Aquaporin-4 (AQP4), a water channel protein expressed in astrocytes, regulates the progression of neurological diseases. Our previous work demonstrated that AQP4 deficiency in mice attenuated morphine-induced physiological dependence. However, the role of AQP4 in the neurobiology of behaviours related to opioid addiction in mice remains unclear. Here, we report that Aqp4-knockout mice exhibited attenuated heroin consumption and heroin-seeking behaviours. Furthermore, Aqp4-knockout mice displayed diminished hyperactivity induced by morphine and heroin and subsequently showed dramatically inhibited morphine-induced behavioural sensitization. This attenuated hyperlocomotion to opioids was accompanied by a decreased dopamine response to the opioid-induced increase in the levels of extracellular dopamine in the NAc. In addition, Aqp4-knockout mice displayed upregulation of dopamine transporters in the striatum, suggesting a probable neurobiological mechanism for uptake of the extracellular dopamine. The present findings suggest that deficiency of AQP4 decreases opiate-induced drug seeking and taking behaviours, and AQP4 may be involved in the treatment of addiction. Therefore, the development of a pharmacological antagonist to AQP4 may be valuable to investigate as opioid addiction therapy.

Impediment of Cerebrospinal Fluid Drainage Through Glymphatic System in Glioma.

BackgroundCerebrospinal fluid (CSF) plays an important role in maintaining tissue homeostasis in the central nervous system. In 2012, the new CSF outflow pathway, “the glymphatic system,” was discovered. The glymphatic system mediates CSF and interstitial fluid exchange through the perivascular pathway, which eliminates harmful solutes in the brain parenchyma. In recent studies, the importance of the glymphatic system has been demonstrated in healthy and neurodegenerative disease brains. However, there is limited research on the function of the CSF in brain tumors. Intracranial hypertension caused by glioma can affect CSF drainage, which impacts the delivery of chemotherapy drugs via intrathecal injection. This study focused on changes in the glymphatic system and the role of aquaporin 4 (AQP4) in glymphatic transport in glioma.MethodsIn glioma-bearing rats, the effect of tracer infusion on the intracranial pressure (ICP) was evaluated using an ICP microsensor. In vivo magnetic resonance imaging and ex vivo bright field were used to monitor CSF tracer distribution after cisterna magna injection. AQP4 expression was quantitatively detected, and AQP4 in the astrocytes around the vessels was observed using immunofluorescence.ResultsThe ICP of the tumor group was higher than that of the control group and the infusion rate of 2 µl/min did not affect ICP. In vivo and ex vivo imaging showed that the circulation of CSF tracers was significantly impaired in the tumor. High-power confocal microscopy revealed that, in the tumor, the surrounding of AQP4 by Evans Blue was decreased. In both tumor and contralateral areas, data indicated that the number of cluster designation 34 (CD34+) alpha-smooth muscle actin (α-SMA−) veins were more than that of CD34+α-SMA+ arteries. Moreover, in the tumor area, AQP4 in the astrocytes around the vessels was decreased.ConclusionsThese findings indicate that the para-arterial influx of subarachnoid CSF is limited in glioma, especially in those with reduced levels of the fundamental protein AQP4. Our results provide evidence toward a potential new treatment method for glioma in the future.

The role of aquaporin 4 (AQP4) in spinal cord injury.

Aquaporin-4 (AQP-4) is an aquaporin composed of six helical transmembrane domains and two highly conserved ASN-pro-ALA (NPA) motifs. It is strongly expressed in rodent and human spinal cord tissues and plays a key role in the pathological process after SCI. After SCI, edema, glial scarring, and inflammation can accelerate the progression of injury and lead to deterioration of function. Many studies have reported that AQP-4 plays an important role in SCI. In particular, it plays an important role in secondary pathological processes (spinal cord edema, glial scar formation, and inflammatory response) after SCI. Loss of AQP-4 has been associated with reduced spinal edema and improved prognosis after SCI in mice. In addition, downregulation of AQP-4 reduces glial scar formation and the inflammatory response after SCI. There is a consensus from numerous studies that AQP-4 may be a potential target for SCI therapy, which guides the ongoing investigation for molecular therapy of SCI. Here, we review the structure of AQP-4, its expression in normal and damaged spinal cord, and its role in SCI, as well as discuss the theoretical basis for the treatment of SCI.

Cerebral Microcirculation, Perivascular Unit, and Glymphatic System: Role of Aquaporin-4 as the Gatekeeper for Water Homeostasis.

In the past, water homeostasis of the brain was understood as a certain quantitative equilibrium of water content between intravascular, interstitial, and intracellular spaces governed mostly by hydrostatic effects i.e., strictly by physical laws. The recent achievements in molecular bioscience have led to substantial changes in this regard. Some new concepts elaborate the idea that all compartments involved in cerebral fluid homeostasis create a functional continuum with an active and precise regulation of fluid exchange between them rather than only serving as separate fluid receptacles with mere passive diffusion mechanisms, based on hydrostatic pressure. According to these concepts, aquaporin-4 (AQP4) plays the central role in cerebral fluid homeostasis, acting as a water channel protein. The AQP4 not only enables water permeability through the blood-brain barrier but also regulates water exchange between perivascular spaces and the rest of the glymphatic system, described as pan-cerebral fluid pathway interlacing macroscopic cerebrospinal fluid (CSF) spaces with the interstitial fluid of brain tissue. With regards to this, AQP4 makes water shift strongly dependent on active processes including changes in cerebral microcirculation and autoregulation of brain vessels capacity. In this paper, the role of the AQP4 as the gatekeeper, regulating the water exchange between intracellular space, glymphatic system (including the so-called neurovascular units), and intravascular compartment is reviewed. In addition, the new concepts of brain edema as a misbalance in water homeostasis are critically appraised based on the newly described role of AQP4 for fluid permeation. Finally, the relevance of these hypotheses for clinical conditions (including brain trauma and stroke) and for both new and old therapy concepts are analyzed.

Abstract 10509: Aquaporin 1 Differentially Controls Endothelial Cell Senescence by Epigenetic and SASP Modulation

Introduction: Aquaporin 1 (AQP1) has been implicated in oxidant sensing, but little is known about its differential role in metabolism and function of proliferating (PEC) and senescent (SEC) endothelial cells. We sought to investigate 1) role of AQP1 in modulation of epigenetic modification and senescence-associated secretory phenotype (SASP) in PEC and SEC, and 2) reversal effects of Aqp1 deletion/inhibition on endothelial senescence and dysfunction. Methods: We executed Aqp1 deletion or selective blockade of AQP1 pore (with Bacopaside II 10 μM) to inhibit H 2 O 2 transport in human aortic endothelial cells (PEC p.5 vs SEC p.15 ) and examined its effects on cellular senescence (via SA-β-galactosidase staining) and function (via in vitro angiogenesis and migration assays), and H 2 O 2 -modulated epigenetic modification and SASP (via biochemical assays). Results: We found that AQP1 facilitates physiological H 2 O 2 supply which is necessary for angiogenesis and cell migration in PEC accompanied by marked increase in AMPK T172 phosphorylation and inhibition of acetyl-coA carboxylase (ACC) that provides acetyl-coA for an increased histone 3 (H3) acetylation. Importantly, Aqp1 deletion/inhibition significantly induced senescence and mitochondrial dysfunction in PEC associated with increased SA-β-gal positive cells, upregulated SASP (TNF-α and ICAM-1), and downregulated Idh2. By contrast, decreased AMPK T172 phosphorylation and H3 acetylation accompanied by increased SA-β-gal positive cells, upregulated SASP and mitochondrial dysfunction seen in SEC were reversed by Aqp1 deletion/inhibition. In SEC, we have shown that Aqp1 deletion restores angiogenesis and migration comparable to PEC. Conclusion: We conclude that AQP1 differentially controls metabolism and function in young and senescent ECs via epigenetic and SASP modulation and that AQP1 inhibition represent new possibilities for rejuvenating senescent ECs and treating cardiovascular disease.

Aquaporin 2 regulation: implications for water balance and polycystic kidney diseases.

Targeting the collecting duct water channel aquaporin 2 (AQP2) to the plasma membrane is essential for the maintenance of mammalian water homeostasis. The vasopressin V2 receptor (V2R), which is a GS protein-coupled receptor that increases intracellular cAMP levels, has a major role in this targeting process. Although a rise in cAMP levels and activation of protein kinase A are involved in facilitating the actions of V2R, studies in knockout mice and cell models have suggested that cAMP signalling pathways are not an absolute requirement for V2R-mediated AQP2 trafficking to the plasma membrane. In addition, although AQP2 phosphorylation is a known prerequisite for V2R-mediated plasma membrane targeting, none of the known AQP2 phosphorylation events appears to be rate-limiting in this process, which suggests the involvement of other factors; cytoskeletal remodelling has also been implicated. Notably, several regulatory processes and signalling pathways involved in AQP2 trafficking also have a role in the pathophysiology of autosomal dominant polycystic kidney disease, although the role of AQP2 in cyst progression is unknown. Here, we highlight advances in the field of AQP2 regulation that might be exploited for the treatment of water balance disorders and provide a rationale for targeting these pathways in autosomal dominant polycystic kidney disease.

Aquaporins in regulation of plant protective responses to drought

Plasmolemma permeability is an integral indicator of the functional state of plant cells under stress. Aquaporins (AQPs), specialized transmembrane proteins that form water channels and play an important role in the adaptation of plants to adverse conditions and, in particular, to lack or excess of water, are involved in the formation of the response to drought. The main function of AQPs is to facilitate the movement of water across cell membranes and maintain aqueous cell homeostasis. Under stressful conditions, there is both an increase and decrease in the expression of individual aquaporin genes. Analysis of the data revealed differences in the expression of AQPs genes in stable and sensitive plant genotypes. It turned out that aquaporins in different stress-resistant varieties of the same species also respond differently to drought. The review provides brief information on the history of the discovery of aquaporins, the structure and function of these proteins, summarizes the latest information on the role of aquaporins in the regulation of metabolism and the response of plants to stressors, with particular emphasis on aquaporins in drought protection. The discovery and study of AQPs expands the possibilities of using genetic engineering methods for the selection of new plant species, in particular, more resistant to drought and salinization of the soil, as well as to increase their productivity. The use of aquaporins in biotechnology to improve drought resistance of various species has many prospects.

MO002THE EXPRESSION OF AQUAPORINS IN A MOUSE CEREBRAL ISCHEMIC MODEL WITH MANNITOL EFFECTS

Abstract Background and Aims As the brain edema influences the outcomes of many edematous brain diseases due to the limited intracranial space, the role of aquaporins (AQPs) in brain edema needs to be clarified to advance its treatment especially in increasing ischemic brain diseases. Although the importance of AQP4 at the Blood Brain Barrier (BBB) has been well characterized, the roles of other AQPs is still unknown, especially a relatively new AQP11. As AQP11 is expressed in the brain capillary (Koike S et al. Int J Mol Sci. 17:861, 2016), AQP11 may also be important for the regulation of brain edema. The aim of the present study is to clarify the role of AQP11 in cerebral ischemic model to identify new treatment of cerebral edema. Method AQP expression in the brain was examined by RT-PCR. Common cervical artery was ligated for 15 min to produce ischemic-reperfusion model of brain infarction to induce brain edema. As the first step to study the involvement of AQPs in this process, the mRNA expression of AQP1, AQP4, AQP11 and GFAP were monitored after reperfusion which are expressed at BBB. As mannitol is often employed for the treatment of brain edema, the effects of single or twice doses of 1.1M mannitol 0.1 mL/g body weight i.p. on the expression of AQP1, AQP4 and AQP11 mRNA were examined after 6 h in control mice. Furthermore, hypertonic 2M NaCl was also challenged to simulate the osmotic effect: a single or twice doses of 2M NaCl 0.16 mL/g body weight were administered intraperitoneally, i.p. Results The expression of AQP1 mRNA increased by 20% one and two hours after 15-min ligation, while the expression of AQP4 mRNA decreased transiently just after the ligation but increased at 24 h by 10%. On the other hand, the expression of AQP11 mRNA started to decrease from 30 min after the ligation to continue decreasing up to 24h by 40% in wild mice, while the decrease of AQP11 mRNA only observed at 24h by 20% in AQP11 heterogenous KO mice. A single mannitol i.p. did not change serum osmolality from 320 to 317 mOsm, while twice i.p. in 6 h interval increased serum osmolality to 328 mOsm. Both procedures similarly decreased the expression of all AQPs: AQP1 by 80%, AQP4 by 40%, and AQP11 by 50%. Similar studies were conducted with 2M NaCl. A single dose of 2M NaCl increased serum Na/Osm from 151/319 to 154/322 mEq/mOsm, which decreased AQP1 by 50%, AQP11 by 35% and no change of AQP4. On the other hand, twice doses in 3 h interval increased serum Na/Osm to 208/435 mEq/Osm, which did not change all AQP expressions. Conclusion As AQP4 KO mice survive longer in brain edema models, decrease of AQP4 by mannitol will be beneficial as brain infarction increased AQP4 expression in our study. However, further decrease of AQP11 by mannitol will be detrimental as AQP11 was already decreased in brain infarction. As AQP11 KO mice die within a month due to polycystic kidneys, the studies on brain infarction in brain capillary specific AQP11 conditionaly KO mice are currently underway.

Role of AQP3 in the Vascular Leakage of Sepsis and the Protective Effect of Ss-31.

Aquaporins (AQPs) are a group of membrane proteins related to water permeability. Studies have shown that AQPs play a vital role in various diseases. Whether AQPs participate in regulating vascular permeability after sepsis and whether the subtype of AQPs is related are unknown. Ss-31, as a new antioxidant, had protective effects on a variety of diseases. However, whether Ss-31 has a protective effect on pulmonary vascular permeability in sepsis and whether its effect is related to AQPs are unclear. Using the cecum ligation perforation-induced septic rat and LPS-treated pulmonary vein endothelial cells, the role of AQPs in the regulation of the permeability of pulmonary vascular and its relationship to Ss-31 were studied. The results showed that the pulmonary vascular permeability significantly increased after sepsis, meanwhile the expressions of AQP3, 4, and 12 increased. Among those, the AQP3 was closely correlated with pulmonary vascular permeability. The inhibition of AQP3 antagonized the increase of the permeability of monolayer pulmonary vein endothelial cells. Further study showed that the expression of caveolin-1 (Cav-1) increased and occludin decreased after sepsis. The inhibition of AQP3 antagonized the decrease of Cav-1 and the increase of occludin in sepsis. Antioxidant Ss-31 decreased the expression of AQP3 and ROS levels. At the same time, Ss-31 improved pulmonary vascular permeability and prolonged survival of sepsis rats. In conclusion, AQP3 participates in the regulation of pulmonary vascular permeability after sepsis, and the antioxidant Ss-31 has a protective effect on pulmonary vascular permeability by downregulating the expression of AQP3 and inhibiting ROS production.

Aquaporin 4 expression in the hippocampus in sudden infant death syndrome and sudden unexplained death in childhood

Aquaporin 4 (AQP4) is the main membrane water channel in the brain involved in regulating water homeostasis. The water distribution in neural tissue is often dysregulated after hypoxic neural injury. Previous research has indicated that victims of sudden infant death syndrome (SIDS) and sudden unexplained death in childhood (SUDC) have an underlying brain dysfunction that impairs their critical arousal response to hypoxic stress during sleep. The aim of this study was to determine the expression levels of AQP4 in the hippocampus in SIDS/SUDC cases and controls, and compare the findings with AQP4 genotypes that previously have been shown to be associated with SIDS. Immunochemical staining and morphometry were used to evaluate the density of AQP4-positive astrocytes in 30 SIDS/SUDC cases and 26 controls. AQP4-positive cells were counted in grids covering three layers in the hippocampus, which revealed that their count in any of the layers did not differ significantly between cases and controls. A decline in AQP4 expression was observed for infants older than 12 weeks. The AQP4 expression was lower in infants and children with the rs2075575 CT/TT genotype than in those with the CC genotype. This study indicates that AQP4 expression may be influenced by both age and genotype in infants. The role of AQP4 in the pathogenesis of SIDS remains to be elucidated.

Plant aquaporins: A frontward to make crop plants drought resistant.

Drought stress alters gene expression and causes cellular damage in crop plants. Drought inhibits photosynthesis by reducing the content and the activity of the photosynthetic carbon reduction cycle, ultimately decreasing the crop yield. The role of aquaporins (AQP) in improving the growth and adaptation of crop plants under drought stress is of importance. AQP form channels and control water transport in and out of the cells and are associated with drought tolerance mechanisms. The current review addresses: (1) the evolution of AQPs in plants, (2) the classification of plant AQPs, (3) the role of AQPs in drought alleviation in crop plants, and (4) the phytohormone crosstalk with AQPs in crops exposed to drought stress.

Aquaporins in platelet function

Structurally, aquaporins (AQPs) are small channel proteins with monomers of ~ 30 kDa that are assembled as tetramers to form pores on cell membranes. Aquaporins mediate the conduction of water but at times also small solutes including glycerol across cell membranes and along osmotic gradients. Thirteen isoforms of AQPs have been reported in mammalian cells, and several of these are likely expressed in platelets. Osmotic swelling mediated by AQP1 sustains the calcium entry required for platelet phosphatidylserine exposure and microvesiculation, through calcium permeable stretch-activated or mechanosensitive cation channels. Notably, deletion of AQP1 diminishes platelet procoagulant membrane dynamics in vitro and arterial thrombosis in vivo, independent of platelet granule secretion and without affecting hemostasis. Water entry into platelets promotes procoagulant activity, and AQPs may also be critical for the initiation and progression of venous thrombosis. Platelet AQPs may therefore represent valuable targets for future development of a new class of antithrombotics, namely, anti-procoagulant antithrombotics, that are mechanistically distinct from current antithrombotics. However, the structure of AQPs does not make for easy targeting of these channels, hence they remain elusive drug targets. Nevertheless, thrombosis data in animal models provide compelling reasons to continue the pursuit of AQP-targeted antithrombotics. In this review, we discuss the role of aquaporins in platelet secretion, aggregation and procoagulation, the challenge of drugging AQPs, and the prospects of targeting AQPs for arterial and venous antithrombosis.

The role of aquaporin-4 in optic nerve head astrocytes in experimental glaucoma.

To study aquaporin channel expression in astrocytes of the mouse optic nerve (ON) and the response to IOP elevation in mice lacking aquaporin 4 (AQP4 null). C57BL/6 (B6) and AQP4 null mice were exposed to bead-induced IOP elevation for 3 days (3D-IOP), 1 and 6 weeks. Mouse ocular tissue sections were immunolabeled against aquaporins 1(AQP1), 4(AQP4), and 9(AQP9). Ocular tissue was imaged to identify normal AQP distribution, ON changes, and axon loss after IOP elevation. Ultrastructure examination, cell proliferation, gene expression, and transport block were also analyzed. B6 mice had abundant AQP4 expression in Müller cells, astrocytes of retina and myelinated ON (MON), but minimal AQP4in prelaminar and unmyelinated ON (UON). MON of AQP4 nulls had smaller ON area, smaller axon diameter, higher axon density, and larger proportionate axon area than B6 (all p≤0.05). Bead-injection led to comparable 3D-IOP elevation (p = 0.42) and axonal transport blockade in both strains. In B6, AQP4 distribution was unchanged after 3D-IOP. At baseline, AQP1 and AQP9 were present in retina, but not in UON and this was unaffected after IOP elevation in both strains. In 3D-IOP mice, ON astrocytes and microglia proliferated, more in B6 than AQP4 null. After 6 week IOP elevation, axon loss occurred equally in the two mouse types (24.6%, AQP4 null vs. 23.3%, B6). Lack of AQP4 was neither protective nor detrimental to the effects of IOP elevation. The minimal presence of AQP4 in UON may be a vital aspect of the regionally specific phenotype of astrocytes in the mouse optic nerve head.

Osmotic adaptation of nucleus pulposus cells: the role of aquaporin 1, aquaporin 4 and transient receptor potential vanilloid 4.

The microenvironment of the nucleus pulposus is hyperosmotic and fluctuates diurnally due to mechanical loading. Changes in extracellular osmolality result in cell volume alterations, responsiveness to such changes is essential for cellular homeostasis. Aquaporins allow movement of water across cell membranes and control water permeability in response to osmotic gradients. Furthermore, transient receptor potential vanilloid 4 has been shown to sense osmotic and mechanical stimuli resulting in changes to intracellular Ca2+. It has been shown previously that aquaporin 1 and 4 expression decreases during disc degeneration. Here, the expression of transient receptor potential vanilloid 4 by human nucleus pulposus cells during disc degeneration, and the roles of aquaporin 1, 4 and transient receptor potential vanilloid 4 in regulating responses to osmotic gradients was investigated. Transient receptor potential vanilloid 4 was expressed by the majority of human nucleus pulposus cells and not affected by disc degeneration. Aquaporin 4 staining co-localised with primary cilia. Nucleus pulposus cells modulated their rate of volume change, water permeability and Ca2+ influx in response to extracellular osmolality. These responses were inhibited by chemical inhibition of aquaporin 4, transient receptor potential vanilloid 4, and to a lesser extent aquaporin 1; suggesting that both aquaporins and transient receptor potential vanilloid 4 play important roles in the fundamental adaptation of nucleus pulposus cells to their osmotic environment. Co-localisation with primary cilia indicates these proteins may function synergistically to achieve adaptation, which may be lost during disc degeneration, when aquaporin 1 and 4 expression is reduced.