title: Is Upregulation of Aquaporin 4-M1 Isoform Responsible for the Loss of Typical Orthogonal Arrays of Particles in Astrocytomas?
abstract: The astrocytic endfoot membranes of the healthy blood-brain barrier-contacting the capillary-are covered with a large number of the water channel aquaporin 4 (AQP4). They form orthogonal arrays of particles (OAPs), which consist of AQP4 isoform M1 and M23. Under pathologic conditions, AQP4 is distributed over the whole cell and no or only small OAPs are found. From cell culture experiments, it is known that cells transfected only with AQP4-M1 do not form OAPs or only small ones. We hypothesized that in astrocytomas the situation may be comparable to the in vitro experiments expecting an upregulation of AQP4-M1. Quantitative Real-time PCR (qRT-PCR) of different graded astrocytomas revealed an upregulation of both isoforms AQP4 M1 and M23 in all astrocytomas investigated. In freeze fracture replicas of low-grade malignancy astrocytomas, more OAPs than in high-grade malignancy astrocytomas were found. In vitro, cultured glioma cells did not express AQP4, whereas healthy astrocytes revealed a slight upregulation of both isoforms and only a few OAPs in freeze fracture analysis. Taken together, we found a correlation between the decrease of OAPs and increasing grade of malignancy of astrocytomas but this was not consistent with an upregulation of AQP4-M1 in relation to AQP4 M23.
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital of Tuebingen, Liebermeisterstr. 8, 72076 Tuebingen, Germany. petra.fallier-becker@med.uni-tuebingen.de.
authors.forename: Petra
authors.initials: P
authors.lastname: Fallier-Becker
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital of Tuebingen, Liebermeisterstr. 8, 72076 Tuebingen, Germany. maike.nieser@med.uni-tuebingen.de.
authors.forename: Maike
authors.initials: M
authors.lastname: Nieser
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital of Tuebingen, Liebermeisterstr. 8, 72076 Tuebingen, Germany. ulrike.wenzel@med.uni-tuebingen.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Wenzel
authors.affiliation: Department of Neurosurgery, Schwarzwald-Baar Klinikum, Klinikstr. 11, 78052 Villingen-Schwenningen, Germany. rainer_ritz@hotmail.com.
authors.forename: Rainer
authors.initials: R
authors.lastname: Ritz
authors.affiliation: Department of Neurosurgery, University Hospital of Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany. dr.susan.noell@googlemail.com.
authors.forename: Susan
authors.initials: S
authors.lastname: Noell
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000235:genetics*; D001253:Astrocytes / Q000166:cytology* / Q000378:metabolism; D001254:Astrocytoma / Q000235:genetics / Q000473:pathology*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology; D006801:Humans; D021621:Imaging, Three-Dimensional; D051379:Mice; D008856:Microscopy, Fluorescence; D020033:Protein Isoforms; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D020033:Protein Isoforms
keywords: aquaporin; high-grade astrocytoma; low-grade astrocytoma; malignancy