title: Alterations in Ca2+ signaling, and c-fos and nur77 expression are associated with sodium butyrate-induced differentiation of C6 glioma cell.
abstract: Sodium butyrate is well known in stimulating growth and differentiation of cancer cells. In the present study, butyrate treatment caused decreases in thymidine incorporation in the early passages (45-60) of C6 glioma cells. In addition, butyrate also caused decreases in inositol incorporation and transient ATP-stimulated Ca2+ mobilization suggesting that butyrate altered general mechanisms of Ca2+ signaling in these cells. To gain direct insight into the crosstalk between sodium butyrate and Ca2+ signaling in transcriptional regulation, we investigated the induction of the Ca2+-sensitive immediate early genes (IEGs), c-fos, nur77 and c-myc. Sodium butyrate per se enhanced the expression of c-fos mRNA, and the enhanced levels were maintained for 24 h, but over the same time period, the initially increased levels of nur77 expression tailed off, while c-myc expression was slightly reduced. Increasing intracellular Ca2+ concentration ([Ca2+]i) by thapsgargin and A23187 induced the expression of both c-fos and nur77 mRNA expression, and synergistic effects were observed when cells were incubated with sodium butyrate plus thapsgargin and A23187. However, removal of both extracellular Ca2+ by EGTA, or intracellular free Ca2+ with BAPTA did not affect the sodium butyrate-induced c-fos and nur77 mRNA. These results suggest that although sodium butyrate altered Ca2+ signaling which is an important regulatory mechanism for c-fos and nur77 expression, nevertheless the sodium butyrate-induced c-fos and nur77 expression may be not in fact mediated through Ca2+ signaling.
authors: Institute of Neuroscience, College of Life Science, National Yang-Ming University, Taipei, Taiwan, ROC.
authors: T H
authors: TH
authors: Jang
authors: S H
authors: SH
authors: Sun
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D002118:Calcium / Q000493:pharmacokinetics; D020013:Calcium Signaling / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics*; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005910:Glioma; D007294:Inositol / Q000378:metabolism / Q000494:pharmacology; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D019284:Thapsigargin / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000166:cytology
chemical_list: D002087:Butyrates; D002614:Chelating Agents; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D014316:Tritium; D007294:Inositol; D004533:Egtazic Acid; D019284:Thapsigargin; D000255:Adenosine Triphosphate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D013936:Thymidine