Histone deacetylase inhibitor 4-phenylbutyrate modulates glial fibrillary acidic protein and connexin 43 expression, and enhances gap-junction communication, in human glioblastoma cells

• Published in: European journal of cancer (1990) Vol. 40; no. 7; pp. 1073 - 1081
• Main Authors: Asklund, T., Appelskog, I.B., Ammerpohl, O., Ekström, T.J., Almqvist, P.M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-05-2004; Elsevier
• Subjects: Antineoplastic Agents - pharmacology; Biological and medical sciences; Blotting, Western; Cell Communication - physiology; Connexin 43; Connexin 43 - metabolism; Gap junction; Gap Junctions - metabolism; GFAP; Glial Fibrillary Acidic Protein - metabolism; Glioblastoma - metabolism; Histone Deacetylase Inhibitors; Histone Deacetylases - drug effects; Humans; Immunocytochemistry; Immunohistochemistry; Malignant glioma; Medical sciences; Medicin och hälsovetenskap; Neurology; Pharmacology. Drug treatments; Phenylbutyrates - pharmacology; Phosphorylation; Primary culture; Tumor Cells, Cultured; Tumors; Tumors of the nervous system. Phacomatoses; Western blot; Western blot; Malignant glioma; Phosphorylation; Immunocytochemistry; Primary culture; Connexin 43; Gap junction; GFAP; Human; Nervous system diseases; Glial fibrillary acidic protein; Glioblastoma; Cell junction; Primary culture: Western blot; Pharmacology; Malignant tumor; Connexin; Cancerology; Central nervous system disease; Immunoblotting assay; Inhibitor; Phenylbutyrate; Communication
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2003.11.034

Human glioblastoma cell cultures were established and the expression of glial fibrillary acidic protein (GFAP) and the gap-junction protein connexin 43 (Cx43) was confirmed by Western blot. Following treatment with 4-phenylbutyrate (4-PB), increased concentrations of non-phosphorylated GFAP were seen, while phosphorylated isoforms remained intact. Immunocytochemical staining of glioblastoma cells revealed an intracellular redistribution of GFAP. In addition to cytoplasmic immunostaining, GFAP immunoreactivity was also associated with the nucleus and/or the nuclear membrane. Phosphorylated and non-phosphorylated Cx43 proteins were increased 2- to 5-fold following 4-PB treatment, and were redistributed to areas of the cell surface, participating in cell-to-cell contacts. In addition, functional gap-junction coupling was amplified, as indicated by increased fluorescent dye transfer, and elevated levels of Cx43 protein were detected in parallel with enhanced gap-junction communication. Induced cell differentiation, with improved functional coupling of tumour cells, may be of importance for therapeutic strategies involving intercellular transport of low molecular-weight compounds.