Disease relevance of Aqp4

• In response to dehydration (3 days, -15 % body weight), renal expression of CHIP28 and MIWC were unchanged, whereas expression of AQP-CD and GLIP were increased significantly by 2.18 +/- 0.04 and 1.36 +/- 0.11 fold (SE, n = 5), respectively [1].
• CONCLUSIONS: Cerebral cortical AQP4 expression is up-regulated after normothermic CA, which is attenuated by hypothermia induced before CA [2].
• Cerebral cortical aquaporin-4 expression in brain edema following cardiac arrest in rats [2].
• Down-regulated AQP4 mRNA expression may be one of the molecular mechanisms maintaining water homeostasis in diffusely injured brain exposed to acute hyponatremia [3].
• Decreased hemispheric Aquaporin-4 is linked to evolving brain edema following controlled cortical impact injury in rats [4].

High impact information on Aqp4

• Perivascular astrocyte end-feet contain distinctive orthogonal lattices (square arrays) assembled from 4- to 6-nm intramembrane particles (IMPs) corresponding to individual AQP4 tetramers [5].
• Osmotic homeostasis in the brain involves movement of water through aquaporin-4 (AQP4) membrane channels [5].
• Two isoforms of AQP4 result from translation initiation at methionine residues M1 and M23, but no functional differences are known [5].
• Immunocytochemical analysis of the brain recently revealed that AQP4 has a highly polarized distribution, with marked expression in astrocyte end-feet that surround capillaries and form the glia limitans; however, the structural organization of AQP4 has remained unknown [6].
• Based on this evidence that AQP4 is concentrated in glial square arrays, freeze-fracture methods may now provide biophysical insights regarding neuropathological states in which abnormal fluid shifts are accompanied by alterations in the aggregation state or the molecular architecture of square arrays [6].

Chemical compound and disease context of Aqp4

• RESULTS: (1) in ethanol-treated stomach, both AQP1 and AQP4 increased after 5 min simultaneously with gastritis, then decreased dramatically depending on time [7].
• These results indicate that AQP4 can alter the osmotic fragility of astrocytes and that testosterone can influence brain edema through AQP4 regulation, whereas 17beta-estradiol and dexamethasone cannot [8].
• To confirm the notion that sex steroids and dexamethasone influence brain edema through AQP4 regulation, we investigated the effects of 17beta-estradiol, testosterone, and dexamethasone on the expression of AQP4 in cultured astrocytes [8].
• Sulforaphane enhances aquaporin-4 expression and decreases cerebral edema following traumatic brain injury [9].
• Ifenprodil treatment is associated with a down-regulation of brain aquaporin 4 following cardiac arrest in rats [10].

Biological context of Aqp4

• In searching for a protein responsible for the high transcellular water permeability in lung alveolus, we cloned a 32-kDa water channel (mercurial-insensitive water channel (MIWC)) from a rat lung cDNA library with several novel features [11].
• In contrast, there were no major changes in the abundance of AQP1, AQP4, and several major proximal and distal tubule Na(+) transporters except NHE3 downregulation, which may participate in the increased sodium excretion [12].
• Expression of mRNA of AQPs (AQP-1-AQP-4) was studied by semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) [13].
• Our findings indicate that AQP4 may facilitate osmotically driven water fluxes in the sensory epithelia of the inner ear and thus contribute to the volume and ion homeostasis at these sites [14].
• These studies suggest water/solute transporting roles for MIWC and GLIP in the urinary concentrating mechanism, cerebrospinal fluid absorption, ocular fluid balance, fecal dehydration, and airway humidification [15].

Anatomical context of Aqp4

• To determine whether astrocyte and ependymocyte square arrays contain AQP4, we employed immunogold labeling of SDS-washed freeze-fracture replicas and stereoscopic confirmation of tissue binding [6].
• By in situ hybridization, MIWC showed an unique distribution in cells that do not express CHIP28, including kidney papillary vasa recta, cells lining the subarachnoid space and ventricles in brain, the inner nuclear layer in retina, and the conjunctival epithelium [11].
• Water permeability was strongly increased in Xenopus oocytes expressing MIWC in a mercurial-insensitive manner, in contrast to known water channels [11].
• The MIWC water channel may participate in the urinary concentrating mechanism, the absorption of cerebrospinal fluid, and other physiological processes [11].
• MIWC mRNA expression was highest in brain, followed by eye, trachea, lung, stomach, kidney, and skeletal muscle [1].

Associations of Aqp4 with chemical compounds

• On the other hand, in the CHG group, expression of AQP-1 and AQP-4 were significantly suppressed, and ultrafiltration volume was lost [13].
• The use of PSL with CHG completely restored the expression of AQP-1 and AQP-4, and peritoneal function improved [13].
• In contrast, AQP4 mRNA is strongly expressed in astrocytes, but no expression is found in primary or passaged brain microvessel endothelial cells, or in RBE4 or C6 cells [16].
• There were no significant changes in aquaporin-1, aquaporin-4, or urea transporters [17].
• Exposure to ambient 21% O2 may contribute to increases in AQP-4 and ENaC expression to facilitate water transport across neonatal airway epithelia in the immediate postnatal period [18].

Regulatory relationships of Aqp4

• In retin, AQP1 is expressed approximately six-fold higher than AQP4, the only other aquaporin expressed [19].
• AQP-4 and ENaC expression increase in FDLE cells cultured on uncoated permeant filters compared with matched control cells cultured on filters containing extracellular matrix derived from fetal lung epithelial cells [18].
• In contrast, AQP4 mRNA was selectively expressed in the stomach and small intestine and AQP8 mRNA in the jejunum and colon [20].

Other interactions of Aqp4

• In contrast, the abundance of whole kidney AQP1 (90 +/- 3%) and inner medullary AQP4 (121 +/- 16%) was unchanged in rats with DM [12].
• No effect of mbetaCD treatment on the basolateral distribution of AQP3 and AQP4 was detected [21].
• Immunocytochemistry confirmed the downregulation of AQP3, AQP4, and p-AQP2 [22].
• Potassium channel subunit Kv3.2 and the water channel aquaporin-4 are selectively localized to cerebellar pinceau [23].
• Thus, we investigated the expression, subcellular localization, possible regulation by secretin, and functional activity of AQP4, a mercury-insensitive water channel expressed in other fluid transporting epithelia [24].

Analytical, diagnostic and therapeutic context of Aqp4

• Molecular cloning of a mercurial-insensitive water channel expressed in selected water-transporting tissues [11].
• Expression of AQP-4 was also measured by Western blot analysis [13].
• The immunofluorescence signal with the AQP4 antibody was diffusely distributed throughout the cytoplasm, and there was no evidence for AQP4 expression in either the apical or basolateral membrane of the epithelial cells [25].
• Immunoelectron microscopy demonstrated AQP4 labeling of the basolateral membrane of IMCD cells, with relatively little labeling of intracellular vesicles [26].
• In the TZ group, expression of AQP-1 and AQP-4 were significantly enhanced, in parallel with an increment in ultrafiltration volume [13].

References