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12 pages, 2068 KiB

Open AccessArticle

Changes in Aquaporin 1, 5 and 9 Gene Expression in the Porcine Oviduct According to Estrous Cycle and Early Pregnancy

by Damian Tanski, Agnieszka Skowronska, Maciej Eliszewski, Leszek Gromadzinski, Bartosz Kempisty and Mariusz T. Skowronski

Int. J. Mol. Sci. 2020, 21(8), 2777; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21082777 - 16 Apr 2020

Cited by 4 | Viewed by 2085

Abstract

Aquaporins (AQPs) are a group of small, integral membrane proteins which play an important role in fluid homeostasis in the reproductive system. In our previous study, we demonstrated AQP1, 5 and 9 protein expression and localization in the porcine oviduct. The presence of [...] Read more.

Aquaporins (AQPs) are a group of small, integral membrane proteins which play an important role in fluid homeostasis in the reproductive system. In our previous study, we demonstrated AQP1, 5 and 9 protein expression and localization in the porcine oviduct. The presence of these isoforms could suggest their role in the transport of the ovum to the uterus by influencing the epithelial cells’ production of oviductal fluid. The aim of this study was to evaluate the expression of AQP1, AQP5 and AQP9 in the infundibulum, ampulla and isthmus in the porcine oviduct during the estrous cycle (early luteal phase, days 2–4, medium luteal phase, days 10–12, late luteal phase days 14–16, follicular phase days 18–20) and pregnancy (period before implantation, days 14–16 and after the implantation, days 30–32) using the Real-Time PCR technique. As clearly demonstrated for the first time, AQP1, 5, and 9 gene expression is influenced by the estrus cycle and pregnancy. Furthermore, expression of AQPs in the porcine oviduct may provide the physiological medium that sustains and enhances fertilization and early cleavage-stage embryonic development. Overall, our study provides a characterization of oviduct AQPs, increasing our understanding of fluid homeostasis in the porcine oviduct to successfully establish and maintain pregnancy. Full article

(This article belongs to the Special Issue Aquaporins: Water Channels Essential for Living Organisms 3.0)

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13 pages, 1803 KiB

Open AccessArticle

The Aquaporin-3-Inhibiting Potential of Polyoxotungstates

by Catarina Pimpão, Inês V. da Silva, Andreia F. Mósca, Jacinta O. Pinho, Maria Manuela Gaspar, Nadiia I. Gumerova, Annette Rompel, Manuel Aureliano and Graça Soveral

Int. J. Mol. Sci. 2020, 21(7), 2467; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072467 - 02 Apr 2020

Cited by 36 | Viewed by 4621

Abstract

Polyoxometalates (POMs) are of increasing interest due to their proven anticancer activities. Aquaporins (AQPs) were found to be overexpressed in tumors bringing particular attention to their inhibitors as anticancer drugs. Herein, we report for the first time the ability of polyoxotungstates (POTs), such [...] Read more.

Polyoxometalates (POMs) are of increasing interest due to their proven anticancer activities. Aquaporins (AQPs) were found to be overexpressed in tumors bringing particular attention to their inhibitors as anticancer drugs. Herein, we report for the first time the ability of polyoxotungstates (POTs), such as of Wells–Dawson P₂W₁₈, P₂W₁₂, and P₂W₁₅, and Preyssler P₅W₃₀ structures, to affect aquaporin-3 (AQP3) activity and impair melanoma cell migration. The tested POTs were revealed to inhibit AQP3 function with different effects, with P₂W₁₈, P₂W₁₂, and P₅W₃₀ being the most potent (50% inhibitory concentration (IC₅₀) = 0.8, 2.8, and 3.2 µM), and P₂W₁₅ being the weakest (IC50 > 100 µM). The selectivity of P₂W₁₈ toward AQP3 was confirmed in yeast cells transformed with human aquaglyceroporins. The effect of P₂W₁₂ and P₂W₁₈ on melanoma cells that highly express AQP3 revealed an impairment of cell migration between 55% and 65% after 24 h, indicating that the anticancer properties of these compounds may in part be due to the blockage of AQP3-mediated permeability. Altogether, our data revealed that P₂W₁₈ strongly affects AQP3 activity and cancer cell growth, unveiling its potential as an anticancer drug against tumors where AQP3 is highly expressed. Full article

(This article belongs to the Special Issue Aquaporins: Water Channels Essential for Living Organisms 3.0)

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14 pages, 6039 KiB

Open AccessArticle

Tissue Distribution of the Readthrough Isoform of AQP4 Reveals a Dual Role of AQP4ex Limited to CNS

by Claudia Palazzo, Pasqua Abbrescia, Onofrio Valente, Grazia Paola Nicchia, Shervin Banitalebi, Mahmood Amiry-Moghaddam, Maria Trojano and Antonio Frigeri

Int. J. Mol. Sci. 2020, 21(4), 1531; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041531 - 24 Feb 2020

Cited by 15 | Viewed by 3520

Abstract

Translational readthrough (TRT) of aquaporin-4 (AQP4) has remarkably expanded the importance of this new post-transcriptional mechanism, as well as the regulation potential of AQP4. The TRT isoform of AQP4, named AQP4ex, is central for both AQP4 polarization and water channel activity in the [...] Read more.

Translational readthrough (TRT) of aquaporin-4 (AQP4) has remarkably expanded the importance of this new post-transcriptional mechanism, as well as the regulation potential of AQP4. The TRT isoform of AQP4, named AQP4ex, is central for both AQP4 polarization and water channel activity in the central nervous system (CNS). Here we evaluate the relevance of the TRT mechanism by analyzing whether AQP4ex is also expressed in peripheral tissues and whether the expression of AQP4ex is necessary for its polarized expression as it occurs in perivascular astrocyte processes. To this purpose, AQP4ex null mice were used, and analysis was performed by immunolocalization and immunoblot. The results demonstrate that AQP4ex is expressed in kidney, stomach, trachea and skeletal muscle with the same localization pattern as the canonical AQP4 isoforms. AQP4ex protein levels vary from 6% to about 13% of the total AQP4 protein levels in peripheral tissues. Immunogold electron microscopy experiments demonstrated the localization of AQP4ex at the astrocytic endfeet, and experiments conducted on AQP4ex null mice CNS confirmed that the expression of AQP4ex is necessary for anchoring of the perivascular AQP4. Without the readthrough isoform, AQP4 assemblies are mis-localized, being uniformly distributed on the astrocyte processes facing the neuropile. No alteration of AQP4 polarization was found in AQP4ex null kidney, stomach, trachea or skeletal muscle, suggesting that AQP4ex does not have a role for proper membrane localization of AQP4 in peripheral tissues. We conclude that a dual role for AQP4ex is limited to the CNS. Full article

(This article belongs to the Special Issue Aquaporins: Water Channels Essential for Living Organisms 3.0)

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13 pages, 2685 KiB

Open AccessArticle

Aquaporin 1, 3, and 5 Patterns in Salivary Gland Mucoepidermoid Carcinoma: Expression in Surgical Specimens and an In Vitro Pilot Study

by Mérin Barbara Stamboni, Ágatha Nagli de Mello Gomes, Milena Monteiro de Souza, Katia Klug Oliveira, Claudia Fabiana Joca Arruda, Fernanda de Paula, Barbara Beltrame Bettim, Márcia Martins Marques, Luiz Paulo Kowalski, Clóvis Antônio Lopes Pinto, Victor Elias Arana-Chavez, Silvia Vanessa Lourenço and Cláudia Malheiros Coutinho-Camillo

Int. J. Mol. Sci. 2020, 21(4), 1287; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041287 - 14 Feb 2020

Cited by 9 | Viewed by 3391

Abstract

Salivary gland aquaporins (AQPs) are essential for the control of saliva production and maintenance of glandular structure. However, little is known of their role in salivary gland neoplasia. Salivary gland tumors comprise a heterogeneous group of lesions, featuring variable histological characteristics and diverse [...] Read more.

Salivary gland aquaporins (AQPs) are essential for the control of saliva production and maintenance of glandular structure. However, little is known of their role in salivary gland neoplasia. Salivary gland tumors comprise a heterogeneous group of lesions, featuring variable histological characteristics and diverse clinical behaviors. Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. The aim of this study was to evaluate the expression of AQP1, AQP3, and AQP5 in 24 MEC samples by immunohistochemistry. AQP1 expression was observed in vascular endothelium throughout the tumor stroma. AQP3 was expressed in epidermoid and mucosal cells and AQP5 was expressed in mucosal cells of MEC. These proteins were expressed in the human MEC cell line UH-HMC-3A. Cellular ultrastructural aspects were analyzed by electron microscopy to certificate the tumor cell phenotype. In summary, our results show that, despite the fact that these molecules are important for salivary gland physiology, they may not play a distinct role in tumorigenesis in MEC. Additionally, the in vitro model may offer new possibilities to further investigate mechanisms of these molecules in tumor biology and their real significance in prognosis and possible target therapies. Full article

(This article belongs to the Special Issue Aquaporins: Water Channels Essential for Living Organisms 3.0)

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19 pages, 2880 KiB

Open AccessArticle

Molecular and Functional Characterization of Grapevine NIPs through Heterologous Expression in aqy-Null Saccharomyces cerevisiae

by Farzana Sabir, Sara Gomes, Maria C. Loureiro-Dias, Graça Soveral and Catarina Prista

Int. J. Mol. Sci. 2020, 21(2), 663; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020663 - 19 Jan 2020

Cited by 15 | Viewed by 3559

Abstract

Plant Nodulin 26-like Intrinsic Proteins (NIPs) are multifunctional membrane channels of the Major Intrinsic Protein (MIP) family. Unlike other homologs, they have low intrinsic water permeability. NIPs possess diverse substrate selectivity, ranging from water to glycerol and to other small solutes, depending on [...] Read more.

Plant Nodulin 26-like Intrinsic Proteins (NIPs) are multifunctional membrane channels of the Major Intrinsic Protein (MIP) family. Unlike other homologs, they have low intrinsic water permeability. NIPs possess diverse substrate selectivity, ranging from water to glycerol and to other small solutes, depending on the group-specific amino acid composition at aromatic/Arg (ar/R) constriction. We cloned three NIPs (NIP1;1, NIP5;1, and NIP6;1) from grapevine (cv. Touriga Nacional). Their expression in the membrane of aqy-null Saccharomyces cerevisiae enabled their functional characterization for water and glycerol transport through stopped-flow spectroscopy. VvTnNIP1;1 demonstrated high water as well as glycerol permeability, whereas VvTnNIP6;1 was impermeable to water but presented high glycerol permeability. Their transport activities were declined by cytosolic acidification, implying that internal-pH can regulate NIPs gating. Furthermore, an extension of C-terminal in VvTnNIP6;1M homolog, led to improved channel activity, suggesting that NIPs gating is putatively regulated by C-terminal. Yeast growth assays in the presence of diverse substrates suggest that the transmembrane flux of metalloids (As, B, and Se) and the heavy metal (Cd) are facilitated through grapevine NIPs. This is the first molecular and functional characterization of grapevine NIPs, providing crucial insights into understanding their role for uptake and translocation of small solutes, and extrusion of toxic compounds in grapevine. Full article

(This article belongs to the Special Issue Aquaporins: Water Channels Essential for Living Organisms 3.0)

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14 pages, 2520 KiB

Open AccessArticle

Pituitary Hormones (FSH, LH, PRL, and GH) Differentially Regulate AQP5 Expression in Porcine Ovarian Follicular Cells

by Mariusz T. Skowronski, Patrycja Mlotkowska, Damian Tanski, Ewa Lepiarczyk, Bartosz Kempisty, Lukasz Jaskiewicz, Chandra S. Pareek and Agnieszka Skowronska

Int. J. Mol. Sci. 2019, 20(19), 4914; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20194914 - 03 Oct 2019

Cited by 6 | Viewed by 3813

Abstract

This study aimed to examine the effect of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and growth hormone (GH) on Aquaporin 5 (AQP5) expression in granulosa (Gc) and theca cells (Tc) from medium (MF) and large (LF) ovarian follicles of pigs. The [...] Read more.

This study aimed to examine the effect of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and growth hormone (GH) on Aquaporin 5 (AQP5) expression in granulosa (Gc) and theca cells (Tc) from medium (MF) and large (LF) ovarian follicles of pigs. The results showed that GH significantly decreased the expression of AQP5 in Gc from MF in relation to the control. In the Gc of large follicles, PRL stimulated the expression of AQP5. However, the increased expression of AQP5 in the Tc of LF was indicated by GH and PRL in relation to the control. A significantly higher expression of the AQP5 protein in the Gc from MF and LF was indicated by FSH and PRL. In co-cultures, an increased expression of AQP5 was observed in the Gc from LF incubated with LH, PRL, and GH. A significantly increased expression of AQP5 was also observed in co-cultures of Tc from all type of follicles incubated with LH, whereas PRL stimulated the expression of AQP5 in Tc from MF. Moreover, AQP5 protein expression increased in the co-culture isolated from MF and LF after treatment with FSH, LH, PRL, and GH. AQP5 immunoreactivity was observed in the cytoplasm, mainly in the perinuclear region and endosomes, as well as in the cell membranes of Gc and Tc from the LF and MF. Full article

(This article belongs to the Special Issue Aquaporins: Water Channels Essential for Living Organisms 3.0)

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12 pages, 2847 KiB

Open AccessArticle

Study of the Mechanism Underlying the Onset of Diabetic Xeroderma Focusing on an Aquaporin-3 in a Streptozotocin-Induced Diabetic Mouse Model

by Nobutomo Ikarashi, Nanaho Mizukami, Risako Kon, Miho Kaneko, Ryogo Uchino, Izumi Fujisawa, Natsuko Fukuda, Hiroyasu Sakai and Junzo Kamei

Int. J. Mol. Sci. 2019, 20(15), 3782; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20153782 - 02 Aug 2019

Cited by 17 | Viewed by 3133

Abstract

Xeroderma is a frequent complication in diabetic patients. In this study, we investigated the mechanism underlying the onset of diabetic xeroderma, focusing on aquaporin-3 (AQP3), which plays an important role in water transport in the skin. Dermal water content in diabetic mice was [...] Read more.

Xeroderma is a frequent complication in diabetic patients. In this study, we investigated the mechanism underlying the onset of diabetic xeroderma, focusing on aquaporin-3 (AQP3), which plays an important role in water transport in the skin. Dermal water content in diabetic mice was significantly lower than that in control mice. The expression level of AQP3 in the skin was significantly lower in diabetic mice than in control mice. One week after streptozotocin (STZ) treatment, despite their increased blood glucose levels, mice showed no changes in the expression levels of AQP3, Bmal1, Clock, and D site-binding protein (Dbp) in the skin and 8-hydroxydeoxyguanosine (8-OHdG) in the urine. In contrast, two weeks after STZ treatment, mice showed increases in the blood glucose level, decreases in AQP3, Bmal1, Clock, and Dbp levels, and increases in the urinary levels of 8-OHdG. The results of this study suggest that skin AQP3 expression decreases in diabetes, which may limit water transport from the vessel side to the corneum side, causing dry skin. In addition, in diabetic mice, increased oxidative stress triggered decreases in the expression levels of Bmal1 and Clock in the skin, thereby inhibiting the transcription of Aqp3 by Dbp, which resulted in decreased AQP3 expression. Full article

(This article belongs to the Special Issue Aquaporins: Water Channels Essential for Living Organisms 3.0)

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16 pages, 966 KiB

Open AccessReview

Regulation of AQP4 in the Central Nervous System

by Arno Vandebroek and Masato Yasui

Int. J. Mol. Sci. 2020, 21(5), 1603; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051603 - 26 Feb 2020

Cited by 95 | Viewed by 9049

Abstract

Aquaporin-4 (AQP4) is the main water channel protein expressed in the central nervous system (CNS). AQP4 is densely expressed in astrocyte end-feet, and is an important factor in CNS water and potassium homeostasis. Changes in AQP4 activity and expression have been implicated in [...] Read more.

Aquaporin-4 (AQP4) is the main water channel protein expressed in the central nervous system (CNS). AQP4 is densely expressed in astrocyte end-feet, and is an important factor in CNS water and potassium homeostasis. Changes in AQP4 activity and expression have been implicated in several CNS disorders, including (but not limited to) epilepsy, edema, stroke, and glioblastoma. For this reason, many studies have been done to understand the various ways in which AQP4 is regulated endogenously, and could be regulated pharmaceutically. In particular, four regulatory methods have been thoroughly studied; regulation of gene expression via microRNAs, regulation of AQP4 channel gating/trafficking via phosphorylation, regulation of water permeability using heavy metal ions, and regulation of water permeability using small molecule inhibitors. A major challenge when studying AQP4 regulation is inter-method variability. A compound or phosphorylation which shows an inhibitory effect in vitro may show no effect in a different in vitro method, or even show an increase in AQP4 expression in vivo. Although a large amount of variability exists between in vitro methods, some microRNAs, heavy metal ions, and two small molecule inhibitors, acetazolamide and TGN-020, have shown promise in the field of AQP4 regulation. Full article

(This article belongs to the Special Issue Aquaporins: Water Channels Essential for Living Organisms 3.0)

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15 pages, 1411 KiB

Open AccessReview

Dynamics of Salivary Gland AQP5 under Normal and Pathologic Conditions

by Kazuo Hosoi, Chenjuan Yao, Takahiro Hasegawa, Hiroshi Yoshimura and Tetsuya Akamatsu

Int. J. Mol. Sci. 2020, 21(4), 1182; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21041182 - 11 Feb 2020

Cited by 36 | Viewed by 5332

Abstract

Aquaporin 5 (AQP5) plays an important role in the salivary gland function. The mRNA and protein for AQP5 are expressed in the acini from embryonic days E13-16 and E17-18, respectively and for entire postnatal days. Ligation-reopening of main excretory duct induces changes in [...] Read more.

Aquaporin 5 (AQP5) plays an important role in the salivary gland function. The mRNA and protein for AQP5 are expressed in the acini from embryonic days E13-16 and E17-18, respectively and for entire postnatal days. Ligation-reopening of main excretory duct induces changes in the AQP5 level which would give an insight for mechanism of regeneration/self-duplication of acinar cells. The AQP5 level in the submandibular gland (SMG) decreases by chorda tympani denervation (CTD) via activation autophagosome, suggesting that its level in the SMG under normal condition is maintained by parasympathetic nerve. Isoproterenol (IPR), a β-adrenergic agonist, raised the levels of membrane AQP5 protein and its mRNA in the parotid gland (PG), suggesting coupling of the AQP5 dynamic and amylase secretion-restoration cycle. In the PG, lipopolysaccharide (LPS) is shown to activate mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalings and potentially downregulate AQP5 expression via cross coupling of activator protein-1 (AP-1) and NF-κB. In most species, Ser-156 and Thr-259 of AQP5 are experimentally phosphorylated, which is enhanced by cAMP analogues and forskolin. cAMP-dependent phosphorylation of AQP5 does not seem to be markedly involved in regulation of its intracellular trafficking but seems to play a role in its constitutive expression and lateral diffusion in the cell membrane. Additionally, Ser-156 phosphorylation may be important for cancer development. Full article

(This article belongs to the Special Issue Aquaporins: Water Channels Essential for Living Organisms 3.0)

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