Disease relevance of Aqp1

• AQP1 facilitates hydrostatically driven lung edema but is not required for active near-isosmolar absorption of alveolar fluid [1].
• The renal medulla in most AQP1/AQP3 null mice by age 4 weeks was atrophic and fluid-filled due to the severe polyuria and hydronephrosis [2].
• Role of aquaporins in alveolar fluid clearance in neonatal and adult lung, and in oedema formation following acute lung injury: studies in transgenic aquaporin null mice [3].
• Three hours after intraperitoneal infusion of thiourea, W/D increased to 5.5 and marked pleural effusions appeared, but there were no differences in wild-type and AQP knockout mice [3].
• Two unexpected renal phenotypes of AQP null mice have been discovered recently, including defective proximal tubule cell migration in AQP1 deficiency, and cystic renal disease in AQP11 deficiency [4].

Psychiatry related information on Aqp1

• Increased expression of water channel aquaporin 1 and aquaporin 4 in Creutzfeldt-Jakob disease and in bovine spongiform encephalopathy-infected bovine-PrP transgenic mice [5].
• The expression of AQP2 and UT-A1, but not UT-A2 mRNAs, was increased to the same level as that of the wild type mice in the water deprivation state, indicating that the vasopressin regulatory mechanism was not affected by OREBPdn [6].

High impact information on Aqp1

• The discovery of aquaporin-1 (AQP1) answered the long-standing biophysical question of how water specifically crosses biological membranes [7].
• P(f) was reduced 10-fold by AQP5 deletion and was further reduced by 2- to 3-fold in AQP1/AQP5 double-knockout mice [8].
• We previously studied the role of AQP1 and AQP4 in lung fluid transport using knockout mice [8].
• Deletion of AQP1 in mice results in diminished urinary concentrating ability, possibly related to reduced NaCl- and urea gradient-driven water transport across the outer medullary descending vasa recta (OMDVR) [9].
• Interestingly, urea was also able to drive water movement across the AQP1-independent pathway [9].

Chemical compound and disease context of Aqp1

• There is increasing evidence that the glycerol channel, aquaporin 7(AQP7), has an important role in adipose tissue formation and function - deletion of the gene in a mouse strain leads to obesity and diabetes type 2 if the mice are aged or fed earlier with a high-fat or sucrose diet [10].
• CONCLUSION: Acetazolamide can suppress tumor metastasis, at least in part, by inhibiting the expression of AQP1 [11].
• A murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) was used to evaluate whether aquaporin-1 (AQP1) is involved in lung inflammation and lung edema formation [12].

Biological context of Aqp1

• This article describes new renal physiologic insights revealed by phenotype analysis of aquaporin-knockout mice and the prospects for further basic and clinical developments [13].
• Aquaporin (AQP) water channels provide a major pathway for osmotically driven water movement across epithelial and microvascular barriers in the lung [3].
• Here, we have investigated the long-term consequences of deletion of the AQP1 gene product by profiling abundance changes in transporters expressed in the inner medullas of AQP1 (-/-) mice vs. heterozygotes [AQP1 (+/-)], which have a normal concentrating capacity [14].
• Urea and urine concentrating ability in mice lacking AQP1 and AQP3 [15].
• The up-regulation of AQP1 expression and/or function in corneal endothelium may reduce corneal swelling and opacification following injury [16].

Anatomical context of Aqp1

• These results indicate that osmotically driven water transport across microvessels in adult lung occurs by a transcellular route through AQP1 water channels and that the microvascular endothelium is a significant barrier for airspace-capillary osmotic water transport [1].
• Both approaches indicated a more than twofold reduction in lung water accumulation in AQP1 (-/-) vs. (+/+) mice in response to a 5- to 10-cm H2O increase in pulmonary artery pressure for five minutes [1].
• Here AQP1/AQP3 double knockout mice were generated and analyzed to investigate the functional role of AQP3 in erythrocytes and kidneys [2].
• Using mice deficient in selected aquaporins as controls, we localized AQP1 in fibrocytes in the spiral ligament and AQP4 in supporting epithelial cells (Hensen's, Claudius, and inner sulcus cells) in the organ of Corti [17].
• Evidence against functionally significant aquaporin expression in mitochondria [18].

Associations of Aqp1 with chemical compounds

• Here, we systematically examined the functional consequence of AQP expression in mitochondria by measurement of water and glycerol permeabilities in mitochondrial membrane preparations from rat brain, liver, and kidney and from wild-type versus knock-out mice deficient in AQPs -1, -4, or -8 [18].
• Furthermore, the urea permeability of the IMCD was significantly reduced in AQP1 (-/-) mice [14].
• Chloride concentrations (average 155 +/- 13 mM) measured by a fluorescence assay were also not different in tear fluid collected from wildtype vs aquaporin null mice [19].
• Treatment of adult ovariectomized mice with replacement steroids demonstrates an estrogen-induced shift in AQP1 signals from the myometrium to the uterine stromal vasculature, suggesting a role in uterine fluid imbibition [20].
• Immunocytochemistry revealed strong expression of aquaporin water channel AQP5 at the luminal membrane of serous epithelial cells in submucosal glands throughout the mouse nasopharynx and upper airways and AQP4 at the contralateral basolateral membrane in some glands [21].
• Analysis of anterior pituitaries from AQP1 knockout mice showed reduced prohormone convertase 1/3, carboxypeptidase E, and ACTH levels compared to wild-type mice demonstrating that our results observed in AtT20 cells can be extended to the animal model [22].

Regulatory relationships of Aqp1

• Heat shock treatment promoted hypertonicity-induced AQP1 and heat shock protein 70 (HSP70) expression in both N100 and N150, suggesting an effect on the stability of hypertonicity-induced AQP1 expression [23].
• Aquaporin-1 (AQP1) is a water channel that is strongly expressed at the ventricular-facing surface of choroid plexus epithelium [24].

Other interactions of Aqp1

• Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice [1].
• Expression of aquaporin 1 and 5 in the developing mouse inner ear and audiovestibular assessment of an Aqp5 null mutant [25].
• Immunoblot analysis indicated no differences in protein expression of AQP1, AQP2, or AQP3, and immunoperoxidase showed no differences in staining patterns [26].
• Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3 [2].
• As in the AQP1 knockout mice, ClC-nK1 (-/-) mice showed decreased expression of UT-A1 and increased expression of beta-ENaC and gamma-ENaC vs. WT controls [14].

Analytical, diagnostic and therapeutic context of Aqp1

• At 5 cm H(2)O outflow pressure, the filtration coefficient was 4.7 cm(3) s(-1) mOsm(-1) and reduced 1.4-fold by AQP1 deletion [27].
• Mice lacking AQP1 have reduced IOP and impaired corneal transparency after swelling, and mice lacking AQP4 have reduced light-evoked potentials by electroretinography [28].
• By in situ hybridization and immunohistochemical techniques, subtle differences between transcript and protein expression patterns were noted for both AQP1 and 5 [25].
• Therefore, AQP1 provides a major route for osmotically driven water transport across the peritoneal barrier in peritoneal dialysis [29].
• Immunofluorescence showed AQP1 protein in capillary endothelia and mesangium near the peritoneal surface and AQP4 in adherent muscle plasmalemma [29].

References