Role Of Aquaporins Research Articles

Pancreatic Aquaporin-7: A Novel Target for Anti-diabetic Drugs?

Aquaporins comprise a family of 13 members of water channels (AQP0-12) that facilitate a rapid transport of water across cell membranes. In some cases, these pores are also permeated by small solutes, particularly glycerol, urea or nitric oxide, among other solutes. Several aquaporins have been identified in the pancreas, an exocrine and endocrine organ that plays an essential role in the onset of insulin resistance and type 2 diabetes. The exocrine pancreas, which accounts for 90% of the total pancreas, secretes daily large volumes of a near-isotonic fluid containing digestive enzymes into the duodenum. AQP1, AQP5, and AQP8 contribute to fluid secretion especially from ductal cells, whereas AQP12 allows the proper maturation and exocytosis of secretory granules in acinar cells of the exocrine pancreas. The endocrine pancreas (10% of the total pancreatic cells) is composed by the islets of Langerhans, which are distributed in α, β, δ, ε, and pancreatic polypeptide (PP) cells that secrete glucagon, insulin, somatostatin, ghrelin and PP, respectively. AQP7, an aquaglyceroporin permeated by water and glycerol, is expressed in pancreatic β-cells and murine studies have confirmed its participation in insulin secretion, triacylglycerol synthesis and proliferation of these endocrine cells. In this regard, transgenic AQP7-knockout mice develop adult-onset obesity, hyperinsulinemia, increased intracellular triacylglycerol content and reduced β-cell mass in Langerhans islets. Moreover, we have recently reported that AQP7 upregulation in β-cells after bariatric surgery, an effective weight loss surgical procedure, contributes, in part, to the improvement of pancreatic steatosis and insulin secretion through the increase of intracytoplasmic glycerol in obese rats. Human studies remain scarce and controversial, with some rare cases of loss-of function mutations of the AQP7 gene being associated with the onset of type 2 diabetes. The present Review is focused on the role of aquaporins in the physiology and pathophysiology of the pancreas, highlighting the role of pancreatic AQP7 as a novel player in the control of β-cell function and a potential anti-diabetic-drug.

Age-Related Changes in Water Transport by Corneal Endothelial Cells in Rats

Senescence-associated alterations in structure and function of cornea make it more sensitive to traumas and disease. Trauma of cornea leads to edema and vision impairment and only corneal transplantation remains the effective for vision correction. Role of aquaporins for cornea endothelium function, as well as age-related changes of their activity, are not entirely understood. Herein, we studied changes with age the water permeability (Pf) of the plasma membranes of the corneal endothelial cells and the level of expression in them of the mRNA genes of the water channels of the aquaporins AQP1 and AQP3 in Wistar and senescence-accelerated OXYS rats. From the age of 3 to 18 months, Pf in Wistar rats increased, in OXYS - decreased and was twice lower than in Wistar rats. The expression of aqp1 mRNA (studied by RT-PCR) in the endothelium was the same in Wistar and OXYS rats at the age of 3 months. By the age of 18 months, it increased only in Wistar rats and became twice higher than in OXYS rats. The expression of aqp3 mRNA in the endothelium of 3-month-old OXYS rats was half that of Wistar rats and did not change with age, while in Wistar rats it decreased and at 18 months was 4 times lower than in 3 months. We supposed that increased water permeability of endothelial cells in Wistar rats is adaptive and compensates for the decrease in endothelial cell density with age, while the accelerated aging of OXYS rats abolishes this compensation.

Renal aquaporin-4 associated pathology in TG-26 mice

Human immunodeficiency virus-associated nephropathy (HIVAN) is a leading cause of end-stage renal disease in HIV patients, which is characterized by glomerulosclerosis and renal tubular dysfunction. Aquaporin-4 (AQP-4) is a membrane bound water channel protein that plays a distinct role in water reabsorption from renal tubular fluid. It has been proven that failure of AQP-4 insertion into the renal tubular membrane leads to renal dysfunction. However, the role of AQP-4 in HIVAN is unclear. We hypothesize that impaired water reabsorption leads to renal injury in HIVAN, where AQP-4 plays a crucial role. Renal function is assessed by urinary protein and serum blood urea nitrogen (BUN). Kidneys from HIV Transgenic (TG26) mice (HIVAN animal model) were compared to wild type mice by immunostaining, immunoblotting and quantitative RT-PCR. TG26 mice had increased proteinuria and BUN. We found decreased AQP-4 levels in the renal medulla, increased endothelin-1, endothelin receptor A and reduced Sirtuin1 (SIRT-1) levels in TG26 mice. Also, oxidative and endoplasmic reticulum stress was enhanced in kidneys of TG26 mice. We provide the first evidence that AQP-4 is inhibited due to induction of HIV associated stress in the kidneys of TG26 mice which limits water reabsorption in the kidney which may be one of the cause associated with HIVAN, impairing kidney physiology. AQP-4 dysregulation in TG26 mice suggests that similar changes may occur in HIVAN patients. This work may identify new therapeutic targets to be evaluated in HIVAN.

Atomic scale simulation of H2O2 permeation through aquaporin: toward the understanding of plasma cancer treatment

Experiments have demonstrated the potential selective anticancer capacity of cold atmospheric plasmas (CAPs), but the underlying mechanisms remain unclear. Using computer simulations, we try to shed light on the mechanism of selectivity, based on aquaporins (AQPs), i.e. transmembrane protein channels transferring external H2O2 and other reactive oxygen species, created e.g. by CAPs, to the cell interior.Specifically, we perform molecular dynamics simulations for the permeation of H2O2 through AQP1 (one of the members of the AQP family) and the palmitoyl-oleoyl-phosphatidylcholine (POPC) phospholipid bilayer (PLB). The free energy barrier of H2O2 across AQP1 is lower than for the POPC PLB, while the permeability coefficient, calculated using the free energy and diffusion rate profiles, is two orders of magnitude higher. This indicates that the delivery of H2O2 into the cell interior should be through AQP.Our study gives a better insight into the role of AQPs in the selectivity of CAPs for treating cancer cells.

Composite Transport Model and Water and Solute Transport across Plant Roots: An Update.

The present review examines recent experimental findings in root transport phenomena in terms of the composite transport model (CTM). It has been a well-accepted conceptual model to explain the complex water and solute flows across the root that has been related to the composite anatomical structure. There are three parallel pathways involved in the transport of water and solutes in roots – apoplast, symplast, and transcellular paths. The role of aquaporins (AQPs), which facilitate water flows through the transcellular path, and root apoplast is examined in terms of the CTM. The contribution of the plasma membrane bound AQPs for the overall water transport in the whole plant level was varying depending on the plant species, age of roots with varying developmental stages of apoplastic barriers, and driving forces (hydrostatic vs. osmotic). Many studies have demonstrated that the apoplastic barriers, such as Casparian bands in the primary anticlinal walls and suberin lamellae in the secondary cell walls, in the endo- and exodermis are not perfect barriers and unable to completely block the transport of water and some solute transport into the stele. Recent research on water and solute transport of roots with and without exodermis triggered the importance of the extension of conventional CTM adding resistances that arrange in series (epidermis, exodermis, mid-cortex, endodermis, and pericycle). The extension of the model may answer current questions about the applicability of CTM for composite water and solute transport of roots that contain complex anatomical structures with heterogeneous cell layers.

Role of mitochondrial dysfunction in the pathogenesis of septic cardiomyopathy

The incidence and mortality of septic cardiomyopathy were high, which is the common cause of death in the patients with sepsis. The pathogenesis of sepsis induced myocardial injury is still unclear. The mitochondrial dysfunction of myocardial cells plays a very important role in the pathophysiological mechanism. This review attempts to introduce the mitochondrial damage of cardiomyocyte from the regulation of mitochondrial energy metabolism, the mechanism of mitochondrial damage, the role of aquaporin and the adjustment of mitochondrial dynamic, in order to provide help for the early prevention of septic cardiomyopathy.

Role of Aquaporins in Determining Carbon and Nitrogen Status in Higher Plants.

Aquaporins (AQPs) are integral membrane proteins facilitating the transport of water and some small neutral molecules across cell membranes. In past years, much effort has been made to reveal the location of AQPs as well as their function in water transport, photosynthetic processes, and stress responses in higher plants. In the present review, we paid attention to the character of AQPs in determining carbon and nitrogen status. The role of AQPs during photosynthesis is characterized as its function in transporting water and CO2 across the membrane of chloroplast and thylakoid; recalculated results from published studies showed that over-expression of AQPs contributed to 25% and 50% increases in stomatal conductance (gs) and mesophyll conductance (gm), respectively. The nitrogen status in plants is regulated by AQPs through their effect on water flow as well as urea and NH4+ uptake, and the potential role of AQPs in alleviating ammonium toxicity is discussed. At the same time, root and/or shoot AQP expression is quite dependent on both N supply amounts and forms. Future research directions concerning the function of AQPs in regulating plant carbon and nitrogen status as well as C/N balance are also highlighted.

The role of aquaporin in the development of pulmonary diseases

The role of aquaporin in the development of pulmonary diseases

Aquaporins in neurological disorders

Aquaporins (AQPs) are water channel molecules that allow the passage of water through the lipid bilayers of cell membranes. AQP1, AQP4 and AQP9 are expressed in the central nervous system and AQP4 is well known as the target of auto-antibodies in Devic’s neuromyelitis optica. The role of AQPs in facilitating water movements suggests a link with oedema formation and resolution in the brain. Furthermore, AQPs are also involved in process formation in glial cells with a close link to neuroinflammation. This mini-review gives an overview of what is currently known about the role of AQPs in different neurological disorders.

Role of aquaporin 5 in the modulation of uterine contractility in pregnant rats at term

Role of aquaporin 5 in the modulation of uterine contractility in pregnant rats at term

Role of Aquaporin 3 in hydrogen peroxide transport and cellular signaling

Role of Aquaporin 3 in hydrogen peroxide transport and cellular signaling

The Role of Aquaporins in Ocular Lens Homeostasis.

Aquaporins (AQPs), by playing essential roles in the maintenance of ocular lens homeostasis, contribute to the establishment and maintenance of the overall optical properties of the lens over many decades of life. Three aquaporins, AQP0, AQP1 and AQP5, each with distinctly different functional properties, are abundantly and differentially expressed in the different regions of the ocular lens. Furthermore, the diversity of AQP functionality is increased in the absence of protein turnover by age-related modifications to lens AQPs that are proposed to alter AQP function in the different regions of the lens. These regional differences in AQP functionality are proposed to contribute to the generation and directionality of the lens internal microcirculation; a system of circulating ionic and fluid fluxes that delivers nutrients to and removes wastes from the lens faster than could be achieved by passive diffusion alone. In this review, we present how regional differences in lens AQP isoforms potentially contribute to this microcirculation system by highlighting current areas of investigation and emphasizing areas where future work is required.

Analysis of aquaporins from the euryhaline barnacle Balanus improvisus reveals differential expression in response to changes in salinity.

Barnacles are sessile macro-invertebrates, found along rocky shores in coastal areas worldwide. The euryhaline bay barnacle Balanus improvisus (Darwin, 1854) (= Amphibalanus improvisus) can tolerate a wide range of salinities, but the molecular mechanisms underlying the osmoregulatory capacity of this truly brackish species are not well understood. Aquaporins are pore-forming integral membrane proteins that facilitate transport of water, small solutes and ions through cellular membranes, and that have been shown to be important for osmoregulation in many organisms. The knowledge of the function of aquaporins in crustaceans is, however, limited and nothing is known about them in barnacles. We here present the repertoire of aquaporins from a thecostracan crustacean, the barnacle B. improvisus, based on genome and transcriptome sequencing. Our analyses reveal that B. improvisus contains eight genes for aquaporins. Phylogenetic analysis showed that they represented members of the classical water aquaporins (Aqp1, Aqp2), the aquaglyceroporins (Glp1, Glp2), the unorthodox aquaporin (Aqp12) and the arthropod-specific big brain aquaporin (Bib). Interestingly, we also found two big brain-like proteins (BibL1 and BibL2) constituting a new group of aquaporins not yet described in arthropods. In addition, we found that the two water-specific aquaporins were expressed as C-terminal splice variants. Heterologous expression of some of the aquaporins followed by functional characterization showed that Aqp1 transported water and Glp2 water and glycerol, agreeing with the predictions of substrate specificity based on 3D modeling and phylogeny. To investigate a possible role for the B. improvisus aquaporins in osmoregulation, mRNA expression changes in adult barnacles were analysed after long-term acclimation to different salinities. The most pronounced expression difference was seen for AQP1 with a substantial (>100-fold) decrease in the mantle tissue in low salinity (3 PSU) compared to high salinity (33 PSU). Our study provides a base for future mechanistic studies on the role of aquaporins in osmoregulation.

Aquaporin 4 expression on trigeminal satellite glial cells under normal and inflammatory conditions

Abstract Aims Limited information is currently available for the expression and role of Aquaporin 4 (AQP4) (AQ4) in the peripheral nervous system (PNS). It has been demonstrated that AQP4 is expressed in sensory ganglia. Immunohistochemistry has revealed that satellite glial cells (SGCs) surrounding the cell bodies of the primary afferent sensory neurons in these sensory ganglia exclusively express AQP4 at a considerably lower level than what is seen in astrocytes. The pathophysiological relevance of AQP4 in peripheral nociception; however, remains unclear. Hence, this study aimed at investigating AQP4 expression in trigeminal neurons and SGCs under normal and inflammatory conditions relevant to craniofacial pain conditions. Methods Rat trigeminal ganglia (TG) were isolated from adult male Sprague-Dawley rats subjected to a model of trigeminal inflammation evoked by unilateral complete Freund’s adjuvant (CFA) injection in temporomandibular joint. Immunohistochemistry was performed on TG sections of CFA-treated animals. NeuN and GS markers were used for identification of neurons and SGCs, respectively. AQP4 expression was investigated in both ipsilateral and contralateral TG sections. The study protocol was approved by the local ethics committee. Results Co-localization of NeuN-AQP4 and GS-AQP4 were identified in both ipsi and contralateral trigeminal ganglia of the CFA-treated rats. However, we did not detect any difference between the ipsi- and contralateral side in terms of alteration in AQP4 receptor expression. Conclusions AQP4 was expressed both on trigeminal neurons and SGCs and CFA did not cause a remarkable change in AQP4 expression, when ipsilateral and contralateral TG of the test animals was compared. Previously, it has been shown that in a neuropathic pain model no difference is detectable between wild type and AQP4-deficient mice, for mechanical and thermal perception; however, in formalin pain model AQP4-deficient mice have higher thermal pain thresholds. Further investigation is required to clarify role of AQP4 in pain.

AQP-4 AND ITS ROLE IN MAINTAINING THE HYDRIC BALANCE IN THE BRAIN

Aquaporins are a vast family of channel proteins whose main role is the bidirectional transport, depending on the osmotic gradient, of water across the lipid membranes, which have low permeability for this solvent. The aquaporins are also involved in the lipid metabolism, the cell proliferation and migration processes, the transport of glycerol, neuroexcitation and epithelial fluids secretion, having numerous roles such as ensuring the water transport in the central nervous system, the production of CSF, aqueous humor and saliva, epithelial hydration, urine concentration and nervous impulse transmission. Up to now, in mammals there have been identified 13 types of aquaporins, each of them annotated from 0 to 12 (Aqp 0 – Aqp 12). Of these, aquaporin-4 (AQP-4) – located in the astroglia - is the most abundant aquaporin in the brain. Although this type of aquaporin is also present inside the brain parenchyma, especially in the astroglial processes lining the neuronal synapses, AQP-4 is mainly located in the astroglial end-feet adjacent to the ependymocyes or endothelial cells, where its main role is to ensure the bidirectional transport of water between the astroglia and the cerebrospinal fluid (CSF) or blood vessels. The presence of AQP-4 on the surface of astroglial processes promotes, in the initial stages of ischemia, the formation of the cytotoxic oedema, but has a protective role against vasogenic oedema. This review aims to describe the roles of AQP-4, and especially the role that this protein has in maintaining the hydric balance in the brain.

低温下でのイネの水吸収とアクアポリン(セミナー「生物のストレス受容のメカニズム-分子レベルから細胞レベルまで-」)

低温下でのイネの水吸収とアクアポリン(セミナー「生物のストレス受容のメカニズム-分子レベルから細胞レベルまで-」)

The role of aquaporins in pancreatic ductal fluid secretion

The role of aquaporins in pancreatic ductal fluid secretion

Silicon-mediated Improvement in Plant Salinity Tolerance: The Role of Aquaporins.

Silicon (Si) is an abundant and differentially distributed element in soils that is believed to have important biological functions. However, the benefits of Si and its essentiality in plants are controversial due to differences among species in their ability to take up this element. Despite this, there is a consensus that the application of Si improves the water status of plants under abiotic stress conditions. Hence, plants treated with Si are able to maintain a high stomatal conductance and transpiration rate under salt stress, suggesting that a reduction in Na+ uptake occurs due to deposition of Si in the root. In addition, root hydraulic conductivity increases when Si is applied. As a result, a Si-mediated upregulation of aquaporin (PIP) gene expression is observed in relation to increased root hydraulic conductivity and water uptake. Aquaporins of the subclass nodulin 26-like intrinsic proteins are further involved in allowing Si entry into the cell. Therefore, on the basis of available published results and recent developments, we propose a model to explain how Si absorption alleviates stress in plants grown under saline conditions through the conjugated action of different aquaporins.

The role of aquaporins in polycystic ovary syndrome – A way towards a novel drug target in PCOS

Aquaporins (AQPs) are transmembrane proteins, able to transport water (and in some cases also small solutes, e. g. glycerol) through the cell membrane. There are twelve types of aquaporins (AQP1–AQP12) expressed in mammalian reproductive systems. According to literature, many diseases of the reproductive organs are correlated with changes of AQPs expression and their malfunction. That is the case in the polycystic ovary syndrome (PCOS), where dysfunctions of AQPs 7–9 and alterations in its levels occur.In this work, we postulate how AQPs are involved in PCOS-related disorders, in order to emphasize their potential therapeutic meaning as a drug target. Our research allows for a surprising inference, that genetic mutation causing malfunction and/or decreased expression of aquaporins, may be incorporated in the popular insulin-dependent hypothesis of PCOS pathogenesis. What is more, changes in AQP’s expression may affect the folliculogenesis and follicular atresia in PCOS.

AQP4 Association with Amyloid Deposition and Astrocyte Pathology in the Tg-ArcSwe Mouse Model of Alzheimer's Disease.

Amyloid-β deposition in senile plaques is one of the main pathological changes in Alzheimer's disease (AD). We previously reported that aquaporin-4 (AQP4) is redistributed within the astrocytes in cerebral amyloid angiopathy in the tg-ArcSwe mouse model of AD, suggesting that AQP4 may participate in amyloid-β deposition. However, the role of AQP4 in plaque formation is not currently clear. The objective of the current study was to explore the AQP4 distribution within plaques in the tg-ArcSwe mice in more depth by the combined application of immunofluorescence cytochemistry and immunogold electron microscopy. In addition, the astrocyte marker, glial fibrillary acidic protein (GFAP), was studied in association with AQP4. We demonstrated a robust upregulation of AQP4 expression in areas of plaques. Compared to GFAP, AQP4 appeared predominantly at later stages of plaque formation, in older mice, and within the processes of astrocytes. In combination with GFAP, AQP4 differentiated plaques into three progression stages under light microscopy. This suggests that AQP4 expression was associated with amyloid deposition and astrocyte pathology in the Tg-ArcSwe mouse model of AD. This provides novel proof for the involvement of AQP4 in the process of amyloid deposition in AD.