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Int. J. Mol. Sci. 2016, 17(8), 1230;

Is Upregulation of Aquaporin 4-M1 Isoform Responsible for the Loss of Typical Orthogonal Arrays of Particles in Astrocytomas?

Institute of Pathology and Neuropathology, University Hospital of Tuebingen, Liebermeisterstr. 8, 72076 Tuebingen, Germany
Department of Neurosurgery, Schwarzwald-Baar Klinikum, Klinikstr. 11, 78052 Villingen-Schwenningen, Germany
Department of Neurosurgery, University Hospital of Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany
Author to whom correspondence should be addressed.
Academic Editor: Kenichi Ishibashi
Received: 13 June 2016 / Revised: 22 July 2016 / Accepted: 25 July 2016 / Published: 29 July 2016
(This article belongs to the Special Issue Aquaporin)
Full-Text   |   PDF [4998 KB, uploaded 29 July 2016]   |  


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. View Full-Text
Keywords: low-grade astrocytoma; high-grade astrocytoma; malignancy; aquaporin low-grade astrocytoma; high-grade astrocytoma; malignancy; aquaporin

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Fallier-Becker, P.; Nieser, M.; Wenzel, U.; Ritz, R.; Noell, S. Is Upregulation of Aquaporin 4-M1 Isoform Responsible for the Loss of Typical Orthogonal Arrays of Particles in Astrocytomas? Int. J. Mol. Sci. 2016, 17, 1230.

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