title: Intracellular application of TNF-alpha impairs cell to cell communication via gap junctions in glioma cells.
abstract: Human gliomas are the most common class of brain neoplasm. In order to better characterize their response to inflammation, we evaluated the influence of tumor necrosis factor alpha (TNF-alpha) on the coupling behaviour and the membrane resting potential (MRP) of glioma cells (F98 glioma cell line) compared to primary astrocytes. In contrast to cultured primary astrocytes which exhibited a profound inhibition of gap junction mediated intercellular communication (GJIC), extracellular exposure of TNF-alpha to F98 glioma cells gained no effect on the functional coupling. Whereas, intracellular application of TNF-alpha into the glioma cells elicited similar effects as those found in primary astrocytes indicating a compromised accessibility of the TNF-alpha receptor in F98 cells. Western blotting, immunocytochemical staining and real time RT PCR analysis revealed a differential expression and distribution of TNF-alpha receptor 1 (TNFR1) in the glioma cells. Connexin 43 (Cx43) is the major astrocytic gap junction protein which when phosphorylated has been shown to reveal altered gating properties. Here we show that TNF-alpha increases the level of phosphorylated Cx43 in primary astrocytes but not in the F98 glioma cells. Our observations could account for the decreased regulatory effects of TNF-alpha on GJIC of F98 glioma cells.
authors: Department of Neurology, St. Josef-Hospital Bochum, Ruhr-University Bochum, Gudrunstrasse 56, Bochum, Germany. Aiden.Haghikia@rub.de
authors: Aiden
authors: A
authors: Haghikia
authors: Kerstin
authors: K
authors: Ladage
authors: Pauline
authors: P
authors: Lafênetre
authors: Arash
authors: A
authors: Haghikia
authors: Daniel
authors: D
authors: Hinkerohe
authors: Dirk
authors: D
authors: Smikalla
authors: Claus G
authors: CG
authors: Haase
authors: Rolf
authors: R
authors: Dermietzel
authors: Pedro M
authors: PM
authors: Faustmann
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002450:Cell Communication / Q000502:physiology; D018031:Connexin 43 / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D051381:Rats; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D018031:Connexin 43; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha
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