• a water channel protein, is abundantly expressed in astrocytes and plays a key role in the development of brain edema. PMID: 17437301, PMID: 17349777

• the primary cellular water channel in the brain, localized to astrocytic foot processes along the blood-brain barrier and brain-cerebrospinal fluid interface. PMID: 17613234

• a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid (CSF) and blood. PMID: 17347837

• the neuromuscular water channel expressed at the sarcolemma of mammalian fast-twitch fibers that mediates a high water transport rate, which is important during muscle activity. PMID: 17266129

• the major water-selective channel in astroglia throughout the central nervous system, facilitates water movement into and out of the brain. PMID: 16303850

• one of the water channel proteins on the plasma membrane of astrocytes, is up-regulated in various conditions with brain edema. PMID: 16133546

• the main water channel in the brain, is expressed in the perivascular membranes of mouse, rat, and human astrocytes. PMID: 16103109

• the predominant water channel in brain and spinal cord, where it is present mainly on astrocytic endfeet contacting vessels. PMID: 15789430

• a water channel in the brain that has been shown to positively correlate with edema formation. PMID: 15677340

• the major water channel in the brain, expressed predominantly in astroglial cell membranes. PMID: 15208268

• a predominant water channel protein in mammalian brains, which is localized in the astrocyte plasma membrane. PMID: 12081649

• a mercury-insensitive water channel protein, is abundant in the central nervous system and is localized in astrocytes and ependymal cells. PMID: 11311979

Normal Expression

• a water channel protein, is abundantly expressed in astrocytes. PMID: 17879149

• AQP4 is localized on the vascular foot of astrocytes in the central nervous system (CNS) under physiological conditions. PMID: 17645239

• In the sensory retina, aquaporin-4 is expressed by Müller glial cells, predominantly in the inner retina, while aquaporin-1 is expressed mainly in the outer retina. PMID: 16039047

• AQP4 expression in both types of skeletal muscle occurs postnatally. PMID: 17266129

• AQP4 was localized to the basolateral plasma membrane of non-pigmented epithelial (NPE) cells in ciliary epithelium and the posterior iris. PMID: 16525835

• AQP4 and AQP9 are expressed in adult murine subventricular zone (SVZ)-derived neural stem cells (NSCs) (ANSCs) and that their levels of expression and cellular localization are differentially regulated upon ANSC differentiation into neurons and glia. AQP4 (but not AQP9) is expressed in human neural stem cells (NSCs) and their progeny. PMID: 16206164

• In adult retina, aquaporin-4 (AQP4) and inwardly rectifying K(+) (Kir4.1) channels localize to astrocyte and Müller cell membranes facing vascular and vitreous compartments, optimizing clearance of extracellular K(+) and water from the synaptic layers. PMID: 16186376

• Aquaporin-4 (AQP4) is the predominant water channel in the neuropil of the central nervous system. It is expressed primarily in astrocytes, but also occurs in ependymocytes and endothelial cells. A striking feature of AQP4 expression is its polarized distribution in brain astrocytes and retinal Muller cells. PMID: 15561407

• AQP4 was heavily localized to astrocytic processes of the pinceau. PMID: 15488478

• Immunofluorescence and immunoblot experiments performed with affinity purified antibodies revealed that only AQP1 and AQP4 are expressed in mouse skeletal muscle: AQP1 in endothelial cells of continuous capillaries and AQP4 on the plasma membrane of muscle fiber. PMID: 15033928

• Immunolocalization studies in proximal, middle, and distal stomach indicated that aquaporin-4 (AQP4) protein is localized only in parietal cells located in the middle or deep regions of the gastric glands. PMID: 14627352

• Aquaporin-4 (AQP4) is prevalently expressed in the brain and here we summarize data from our findings and from other literature concerning AQP4 expression in the cerebellum and the relationships between its expression and blood-brain barrier differentiation and integrity. PMID: 12879982

• A single Aqp4 isoform was expressed in a highly conserved pattern within the supporting epithelia surrounding the sensory cells of the auditory and vestibular sensory organs and the glial cells surrounding the auditory nerve of the mouse and rat. PMID: 12359252

• AQP4 was found in the cochlear supporting cells, including Claudius cells, Hensen's cells and inner sulcus cells of the 3 rodent species. AQP4 was also expressed in some interdental cells of the spiral limbus. PMID: 12086153

• Aquaporin-4 (AQP4) is a member of the aquaporin water-channel family. AQP4 is expressed primarily in the brain, but it is also present in the collecting duct of the kidney, where it is located in the basolateral plasma membrane of principal cells and inner medullary collecting duct (IMCD) cells. PMID: 11518772

• AQP4 is constitutively expressed on the basolateral cholangiocyte membrane and is secretin unresponsive. PMID: 10827157

• Aquaporin-4 is expressed in basolateral membranes of proximal tubule S3 segments in mouse kidney. PMID: 10662735

Abnormal Expression

• immunohistochemical results indicate that the expression not only of AQP4 but also of AQP1 was enhanced in multiple sclerosis (MS) and ischemic brain lesions located predominantly in astrocytes, PMID: 17645239

• The aquaporin 4 (AQP4) water channel is present on the sarcolemma of fast-twitch-type skeletal myofibres. PMID: 17593398

• expression of AQP4 and AQP8 proteins was reduced in the proximal colon of the allergic mice. PMID: 17574630

• In contrast to multiple sclerosis (MS) lesions, which exhibit stage-dependent loss of AQP4, all neuromyelitis optica (NMO) lesions demonstrate a striking loss of AQP4 regardless of the stage of demyelinating activity, extent of tissue necrosis, or site of CNS involvement. PMID: 17282996

• We have found AQP4 in gray and white matter astrocytes in both uninjured and injured rat spinal cords. PMID: 17074445

• The distribution of neuromyelitis optica (NMO)-characteristic brain lesions corresponds to sites of high AQP4 expression. PMID: 16831965

• AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors. PMID: 15593389

• reactive microglial cells highly express AQP4 mRNA and protein in response to lipopolysaccharide (LPS) injections. PMID: 15525343

• the expression of AQP4 is affected by nerve supply and is down-regulated in human muscles with neurogenic atrophy. PMID: 15200272

• AQP-4 levels significantly increased 10 h after treatment with ammonia, and displayed a progressive rise up to 48 h, which appeared to precede the onset of astrocyte swelling. PMID: 14663195

• AQP4 loss in skeletal muscle correlates with muscular dystrophy and is a common feature of pathogenesis. PMID: 12087055

Diagnostic & Therapeutic Value

• an anti-AQP4 antibody is found not only in multiple sclerosis (MS) patients with long T2 lesions but also in patients with segmental cord atrophy extending more than three vertebral segments. PMID: 17702782

• aquaporin 4 water channel is a target antigen in a majority of patients with Neuromyelitis optica (NMO). The newly developed assay represents a highly specific, observer-independent, and easily reproducible detection method facilitating clinically relevant discrimination between NMO, MS (multiple sclerosis), and other inflammatory diseases. PMID: 17439296

• The finding of increased AQP4 expression in multiple sclerosis (MS) lesions in contrast to the lack of expression in neuromyelitis optica (NMO) lesions may suggest different mechanisms of initiation and progression between the two disease states. PMID: 17143632

• AQP4 inhibition may provide a new therapeutic option for reducing brain edema in a wide variety of cerebral disorders. PMID: 10655103

Applications

Immunoblot (IB)

• We generated the muscle aquaporin 4 (AQP4) overexpressing transgenic mice in order to investigate the skeletal muscle pathology at RNA and protein levels. At protein level examinations, we used the immunoblot, immunohistochemistry and freeze-fracture electron microscopy. PMID: 16820300

• Immunoblots showed that the band of FCMD muscle extracts stained with anti-AQP4 antibody was faint in comparison with that of normal muscle extracts. The immunohistochemistry revealed that most of the FCMD myofibers showed negative immunostaining with anti-AQP4 antibody, although the partially positive immunostaining of sporadic FCMD myofibers was noted. PMID: 12942324

Immuno-Electron Microscopy (IEM)

• Wax and Vibratome sections were immunostained for detection of AQP4 by light and electron microscopy, respectively. PMID: 16671494

• we investigated the ultrasturctural localization of AQP4 and alpha1-syntrophin in the brain astrocytes by using double immunogold labeled electron microscopy. The results showed that AQP4 and alpha1-syntrophin colocalized frequently at the astrocyte membrane. PMID: 12233788

• Immunocytochemistry and high-resolution immunogold electron microscopy revealed highly polarized labeling of AQP4 in astrocyte end-feet surrounding capillaries and forming the glia limitans. PMID: 10753653

• Immunofluorescence and postembedding immunogold labelling revealed a strictly non-epithelial distribution of AQP1, confirming previous data. PMID: 9875338

• Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord. PMID: 9751776

• In situ hybridization with digoxigenin-labeled riboprobes and immunogold labeling by a sensitive postembedding procedure demonstrated that AQP4 and AQP4 mRNA were restricted to glial cells, including MHller cells in the retina and fibrous astrocytes in the optic nerve. A quantitative immunogold analysis of the MHller cells showed that these cells exhibited three distinct membrane compartments with regard to AQP4 expression. PMID: 9502811

Immunofluorescence (IF)

• In the present study, we have established human cell lines that stably express human AQP4 and used these cells to detect and titrate anti-AQP4 antibody present in the sera of patients with neuromyelitis optica (NMO) by immunofluorescence assay. PMID: 17146196

• The present immunofluorescent study reveals the distribution of aquaporin-4 in the circumventricular organs in rat and chicken brains. PMID: 16416308

• Immunofluorescence results indicate that, compared with healthy control children, AQP4 is reduced severely in all the DMD muscular biopsies analyzed and in 50% of the analyzed BMD. Western blot analysis revealed that the deficiency in sarcolemma AQP4 staining is due to a reduction in total AQP4 muscle protein content rather than to changes in immunoreactivity. PMID: 12039847

• Using combined double immunofluorescence and laser confocal microscopy, we studied the common cellular localization of cholinergic muscarinic receptors (mAChRs) and aquaporin-4 water channels (AQP4) in the cortex, the corpus callosum and in ependymal cells of the rat brain. PMID: 10998552

Immunohistochemistry (IHC)

• We studied whether induction of AQP4 correlated with edema formation in a rat pup filament stroke model using high field (11.7-Tesla) MRI followed by immunohistochemical investigation of AQP4 protein expression. PMID: 17622964

• To elucidate the AQP4 role in brain tumors, we investigated 189 WHO grade I-IV gliomas by immunohistochemistry and the prognostic significance for patients' survival. PMID: 17335082

• AQP4 immunoactivity in the cerebral cortex was determined using immunohistochemical staining and was semiquantified as an intensity of staining with an automated cell imaging system. PMID: 15466140

• The purpose of this study was to investigate the expression of AQP1 and AQP4 in human brain after subarachnoid hemorrhage (SAH) and in peritumoral tissue by western blot and immunohistochemistry. PMID: 14753493

• Cellular localization of AQP4 and its relation to ischemic foci were examined with double-labeling immunohistochemistry. AQP4 immunoreactivity (IR) was more intense at the periphery of ischemic foci than at their center. Double-labeling study demonstrated that AQP4 IR was restricted to astrocytes and was localized to their entire processes, including their end feet facing the outer surface of capillaries. PMID: 12715185

• At the protein level, immunohistochemical staining of our originally generated rabbit anti-AQP4 antibody in DMD muscles was markedly reduced. PMID: 11890849

• immunohistochemistry was used to study AQP4 expression in non-neoplastic and neoplastic human brain and blood-brain barrier permeability was assessed using contrast enhanced computed tomograms. AQP4 was massively upregulated in four and absent in one high grade (Daumas-Duport III or IV) astrocytoma. Massive upregulation of AQP4 was also found in reactive astrocytes in five metastatic adenocarcinomas. PMID: 11796780

• Immunohistochemical analysis showed that AQP1 was localized at capillary endothelial cells and fibroblasts in lamina propria mucosae; AQP4 was present solely at the basolateral membrane of ciliated cells, whereas AQP5 was on the apical surface of ciliated cells as well as of flat and columnar epithelial cells. PMID: 11506936

• Immunohistochemically, reactivity for aquaporin-4 was detected in the optic tectum of day-14 embryos; similar results were obtained in telencephalon and cerebellum. Ultrastructurally, the microvessels of the tectum showed immunoreactivity for aquaporin-4 on the astroglial endfeet, which discontinuously surrounded endothelial cells joined by immature tight junctions. PMID: 11256996

• Immunohistochemical experiments revealed that affinity-purified AQP4 antibodies stained selectively the sarcolemma of fast-twitch fibers. By immunogold electron microscopy, little or no intracellular labeling was detected. Western blot analysis showed the presence of two immunopositive bands with apparent molecular masses of 30 and 32 kD specifically present in membrane fraction of a fast-twitch rat skeletal muscle (extensor digitorum longus, EDL) and not revealed in a slow-twitch muscle (soleus). PMID: 9710437

• Immunocytochemistry (light microscopy) revealed renal AQP4 labeling exclusively in the collecting duct principal cells, chiefly in the proximal two-thirds of the inner medullary collecting duct (IMCD). Immunoelectron microscopy demonstrated AQP4 labeling of the basolateral membrane of IMCD cells, with relatively little labeling of intracellular vesicles. PMID: 8594871

Western Blot (WB)

• We used quantitative (real-time) RT-PCR, Western blotting and immunohistochemistry to evaluate the brain expression of aquaporins (AQP) 1, 4, and 9 mRNA and protein in Sprague-Dawley rats rendered hydrocephalic by injection of kaolin into cistern magna. PMID: 16819982

• Whereas Western blot analysis showed an overall increase in AQP4 levels in MTLE compared with non-MTLE hippocampi, quantitative ImmunoGold electron microscopy revealed that the density of AQP4 along the perivascular membrane domain of astrocytes was reduced by 44% in area CA1 of MTLE vs. non-MTLE hippocampi. PMID: 15657133

• Western blot analysis showed that the rabbit antiserum against aquaporin 4 reacted with a 28 kDa protein in extracts of normal mouse quadriceps femoris muscles but did not react with the protein in extracts of quadriceps femoris muscles of mdx mice. PMID: 10385043