scholarly journals Reduction of Skin pH during Treatment for Palmoplantar Hyperhidrosis: A Conjecture on the Role of pH-Regulated Water Channel, i.e. Aquaporin

2013 ◽  
Vol 5 (1) ◽  
pp. 126-128
Author(s):  
Kyoko Nakahigashi ◽  
Takashi Nomura ◽  
Yoshiki Miyachi ◽  
Kenji Kabashima
Keyword(s):  
Water Channel ◽  
Skin Ph

Neuromyelitis optica spectrum: novel concept of pathogenesis, diagnosis and treatment of Devic’s disease

2009 ◽  
Vol 150 (46) ◽  
pp. 2101-2109 ◽  
Author(s):  
Péter Csécsei ◽  
Anita Trauninger ◽  
Sámuel Komoly ◽  
Zsolt Illés
Keyword(s):  
Neuromyelitis Optica ◽  
Water Channel ◽  
Diagnostic Procedures ◽  
Diagnosis And Treatment ◽  
Clinical Settings ◽  
Permanent Disability ◽  
Therapeutic Decisions ◽  
Novel Concept ◽  
The Brain

The identification of autoantibodies generated against the brain isoform water channel aquaporin4 in the sera of patients, changed the current diagnostic guidelines and concept of neuromyelitis optica (NMO). In a number of cases, clinical manifestation is spatially limited to myelitis or relapsing optic neuritis creating a diverse. NMO spectrum. Since prevention of relapses provides the only possibility to reduce permanent disability, early diagnosis and treatment is mandatory. In the present study, we discuss the potential role of neuroimaging and laboratory tests in differentiating the NMO spectrum from other diseases, as well as the diagnostic procedures and therapeutic options. We also present clinical cases, to provide examples of different clinical settings, diagnostic procedures and therapeutic decisions.

Inhibition of the water channel aquaporin-1 prevents myocardial remodeling by blocking the transmembrane transport of hydrogen peroxide

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Montiel ◽  
R Bella ◽  
L Michel ◽  
E Robinson ◽  
J.C Jonas ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Cardiac Hypertrophy ◽  
Cardiac Myocytes ◽  
Cardiac Remodeling ◽  
Cardiac Myocyte ◽  
Water Channel ◽  
Transmembrane Transport ◽  
Funding Source ◽  
Water Pore

Abstract Background Pathological remodeling of the myocardium has long been known to involve oxidant signaling, but so far, strategies using systemic anti-oxidants have generally failed to prevent it. Aquaporins are a family of transmembrane water channels with thirteen isoforms currently known. Some isoforms have been implicated in oxidant signaling. AQP1 is the most abundant aquaporin in cardiovascular tissues but its specific role in cardiac remodeling remains unknown. Purpose We tested the role of AQP1 as a key regulator of oxidant-mediated cardiac remodeling amenable to targeted pharmacological therapy. Methods We used mice with genetic deletion of Aqp1 (and wild-type littermate), as well as primary isolates from the same mice and human iPSC/Engineered Heart Tissue to test the role of AQP1 in pro-hypertrophic signaling. Human cardiac myocyte-specific (PCM1+) expression of AQP's and genes involved in hypertrophic remodeling was studied by RNAseq and bioinformatic GO pathway analysis. Results RNA sequencing from human cardiac myocytes revealed that the archetypal AQP1 is a major isoform. AQP1 expression correlates with the severity of hypertrophic remodeling in patients with aortic stenosis. The AQP1 channel was detected at the plasma membrane of human and mouse cardiac myocytes from hypertrophic hearts, where it colocalizes with the NADPH oxidase-2 (NOX2) and caveolin-3. We show that hydrogen peroxide (H2O2), produced extracellularly, is necessary for the hypertrophic response of isolated cardiac myocytes and that AQP1 facilitates the transmembrane transport of H2O2 through its water pore, resulting in activation of oxidant-sensitive kinases in cardiac myocytes. Structural analysis of the amino acid residues lining the water pore of AQP1 supports its permeation by H2O2. Deletion of Aqp1 or selective blockade of AQP1 intra-subunit pore (with Bacopaside II) inhibits H2O2 transport in mouse and human cells and rescues the myocyte hypertrophy in human induced pluripotent stem cell-derived engineered heart muscle. This protective effect is due to loss of transmembrane transport of H2O2, but not water, through the intra-subunit pore of AQP1. Treatment of mice with clinically-approved Bacopaside extract (CDRI08) inhibitor of AQP1 attenuates cardiac hypertrophy and fibrosis. Conclusion We provide the first demonstration that AQP1 functions as an aqua-peroxiporin in primary rodent and human cardiac parenchymal cells. We show that cardiac hypertrophy is mediated by the transmembrane transport of H2O2 through the AQP1 water channel. Our studies open the way to complement the therapeutic armamentarium with specific blockers of AQP1 for the prevention of adverse remodeling in many cardiovascular diseases leading to heart failure. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): FRS-FNRS, Welbio

Water transport across mammalian cell membranes

1996 ◽  
Vol 270 (1) ◽  
pp. C12-C30 ◽  
Author(s):  
A. S. Verkman ◽  
A. N. van Hoek ◽  
T. Ma ◽  
A. Frigeri ◽  
W. R. Skach ◽  
...  
Keyword(s):  
Water Transport ◽  
Cell Membranes ◽  
Water Channel ◽  
Water Channels ◽  
Channel Structure ◽  
Level Information ◽  
Selective Channel ◽  
Transcriptional Units ◽  
Measurement Strategies

This review summarizes recent progress in water-transporting mechanisms across cell membranes. Modern biophysical concepts of water transport and new measurement strategies are evaluated. A family of water-transporting proteins (water channels, aquaporins) has been identified, consisting of small hydrophobic proteins expressed widely in epithelial and nonepithelial tissues. The functional properties, genetics, and cellular distributions of these proteins are summarized. The majority of molecular-level information about water-transporting mechanisms comes from studies on CHIP28, a 28-kDa glycoprotein that forms tetramers in membranes; each monomer contains six putative helical domains surrounding a central aqueous pathway and functions independently as a water-selective channel. Only mutations in the vasopressin-sensitive water channel have been shown to cause human disease (non-X-linked congenital nephrogenic diabetes insipidus); the physiological significance of other water channels remains unproven. One mercurial-insensitive water channel has been identified, which has the unique feature of multiple overlapping transcriptional units. Systems for expression of water channel proteins are described, including Xenopus oocytes, mammalian and insect cells, and bacteria. Further work should be directed at elucidation of the role of water channels in normal physiology and disease, molecular analysis of regulatory mechanisms, and water channel structure determination at atomic resolution.

Cloning of an aquaporin homologue present in water channel containing endosomes of toad urinary bladder

1996 ◽  
Vol 270 (1) ◽  
pp. C372-C381 ◽  
Author(s):  
J. Siner ◽  
A. Paredes ◽  
C. Hosselet ◽  
T. Hammond ◽  
K. Strange ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Water Channel ◽  
Structural Features ◽  
Xenopus Laevis Oocytes ◽  
Sequence Motif ◽  
Toad Urinary Bladder ◽  
Cytoplasmic Vesicles ◽  
Terrestrial Habitats ◽  
Total Body

Regulation of total body water balance in amphibians by antidiuretic hormone (ADH) contributed to their successful colonization of terrestrial habitats approximately 200-300 million years ago. In the mammalian kidney, ADH modulates epithelial cell apical membrane water permeability (Pf) by fusion and retrieval of cytoplasmic vesicles containing water channel proteins called aquaporins (AQPs). To determine the role of AQPs in ADH-elicited Pf in amphibians, we have identified and characterized a unique AQP from Bufo marinus called AQP toad bladder (AQP-TB). AQP-TB possesses many structural features common to other AQPs, AQP-TB is expressed abundantly in ADH-responsive tissues, including toad urinary bladder and skin as well as lung, skeletal muscle, kidney, and brain. In a manner identical to that reported for the mammalian ADH-elicited water channel AQP2, AQP-TB expression is increased significantly by intervals of dehydration or chronic ADH stimulation. However, expression of AQP-TB protein in Xenopus laevis oocytes does not significantly increase oocyte Pf. The lack of expression of functional AQP-TB water channels in oocytes may result from intracellular sequestration of AQP-TB due to the presence of a YXRF sequence motif present in its carboxyterminal domain.

Regulation of the water channel aquaporin-2 by posttranslational modification

2011 ◽  
Vol 300 (5) ◽  
pp. F1062-F1073 ◽  
Author(s):  
Hanne B. Moeller ◽  
Emma T. B. Olesen ◽  
Robert A. Fenton
Keyword(s):  
Membrane Proteins ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Water Channel ◽  
Cellular Functions ◽  
Aquaporin 2 ◽  
Eukaryotic Membrane Proteins ◽  
Insight Into

The cellular functions of many eukaryotic membrane proteins, including the vasopressin-regulated water channel aquaporin-2 (AQP2), are regulated by posttranslational modifications. In this article, we discuss the experimental discoveries that have advanced our understanding of how posttranslational modifications affect AQP2 function, especially as they relate to the role of AQP2 in the kidney. We review the most recent data demonstrating that glycosylation and, in particular, phosphorylation and ubiquitination are mechanisms that regulate AQP2 activity, subcellular sorting and distribution, degradation, and protein interactions. From a clinical perspective, posttranslational modification resulting in protein misrouting or degradation may explain certain forms of nephrogenic diabetes insipidus. In addition to providing major insight into the function and dynamics of renal AQP2 regulation, the analysis of AQP2 posttranslational modification may provide general clues as to the role of posttranslational modification for regulation of other membrane proteins.

scholarly journals The Deubiquitylase USP4 Interacts with the Water Channel AQP2 to Modulate Its Apical Membrane Accumulation and Cellular Abundance

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 265 ◽  
Author(s):  
Sathish Murali ◽  
Takwa Aroankins ◽  
Hanne Moeller ◽  
Robert Fenton
Keyword(s):  
Collecting Duct ◽  
Water Channel ◽  
Mouse Kidney ◽  
Body Water ◽  
Mrna Levels ◽  
E3 Ligases ◽  
Water Homeostasis ◽  
And Function

Aquaporin 2 (AQP2) mediates the osmotic water permeability of the kidney collecting duct in response to arginine vasopressin (VP) and is essential for body water homeostasis. VP effects on AQP2 occur via long-term alterations in AQP2 abundance and short-term changes in AQP2 localization. Several of the effects of VP on AQP2 are dependent on AQP2 phosphorylation and ubiquitylation; post-translational modifications (PTM) that modulate AQP2 subcellular distribution and function. Although several protein kinases, phosphatases, and ubiquitin E3 ligases have been implicated in AQP2 PTM, how AQP2 is deubiquitylated or the role of deubiquitylases (DUBS) in AQP2 function is unknown. Here, we report a novel role of the ubiquitin-specific protease USP4 in modulating AQP2 function. USP4 co-localized with AQP2 in the mouse kidney, and in mpkCCD14 cells USP4 and AQP2 abundance are increased by VP. AQP2 and USP4 co-immunoprecipitated from mpkCCD14 cells and mouse kidney, and in vitro, USP4 can deubiquitylate AQP2. In mpkCCD14 cells, shRNA mediated knockdown of USP4 decreased AQP2 protein abundance, whereas no changes in AQP2 mRNA levels or VP-induced cAMP production were detected. VP-induced AQP2 membrane accumulation in knockdown cells was significantly reduced, which was associated with higher levels of ubiquitylated AQP2. AQP2 protein half-life was also significantly reduced in USP4 knockdown cells. Taken together, the data suggest that USP4 is a key regulator of AQP2 deubiquitylation and that loss of USP4 leads to increased AQP2 ubiquitylation, decreased AQP2 levels, and decreased cell surface AQP2 accumulation upon VP treatment. These studies have implications for understanding body water homeostasis.

Advances in aquaporin-2 trafficking mechanisms and their implications for treatment of water balance disorders

2020 ◽  
Vol 319 (1) ◽  
pp. C1-C10 ◽  
Author(s):  
Robert A. Fenton ◽  
Sathish K. Murali ◽  
Hanne B. Moeller
Keyword(s):  
Protein Interactions ◽  
Collecting Duct ◽  
Water Channel ◽  
Plasma Osmolality ◽  
Carboxyl Terminus ◽  
Apical Plasma Membrane ◽  
Tail Domain ◽  
Water Reabsorption ◽  
Aquaporin 2

In mammals, conservation of body water is critical for survival and is dependent on the kidneys’ ability to minimize water loss in the urine during periods of water deprivation. The collecting duct water channel aquaporin-2 (AQP2) plays an essential role in this homeostatic response by facilitating water reabsorption along osmotic gradients. The ability to increase the levels of AQP2 in the apical plasma membrane following an increase in plasma osmolality is a rate-limiting step in water reabsorption, a process that is tightly regulated by the antidiuretic hormone arginine vasopressin (AVP). In this review, the focus is on the role of the carboxyl-terminus of AQP2 as a key regulatory point for AQP2 trafficking. We provide an overview of AQP2 structure, disease-causing mutations in the AQP2 carboxyl-terminus, the role of posttranslational modifications such as phosphorylation and ubiquitylation in the tail domain, and their implications for balanced trafficking of AQP2. Finally, we discuss how various modifications of the AQP2 tail facilitate selective protein-protein interactions that modulate the AQP2 trafficking mechanism.

The role of water channel aquaporin 3 in the mechanism of TNF-α-mediated proinflammatory events: Implication in periodontal inflammation

2008 ◽  
Vol 217 (2) ◽  
pp. 338-349 ◽  
Author(s):  
S. Tancharoen ◽  
T. Matsuyama ◽  
K. Abeyama ◽  
K. Matsushita ◽  
K. Kawahara ◽  
...  
Keyword(s):  
Water Channel ◽  
Aquaporin 3 ◽  
Periodontal Inflammation ◽  
Tnf Α
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