title: Regulation of astrocyte nitric oxide synthase type II expression by ATP and glutamate involves loss of transcription factor binding to DNA.
abstract: Pretreatment of astrocytes with either glutamate or ATP, acting via specific receptors, suppresses subsequent cytokine-induced expression of type II nitric oxide synthase (NOS). This effect is downstream from the activation and translocation of nuclear factor (NF)-kappaB, as western blotting revealed no difference in accumulation of the p50 subunit in nuclear extracts from agonist-treated vs. nontreated cells. However, evidence from gel-shift assay suggests that the binding of nuclear protein from agonist-treated cells to NF-kappaB and activator protein-1 consensus oligonucleotides is markedly reduced. Selective inhibitors of protein kinases A and C could not restore either binding of transcription factors to DNA or type II NOS mRNA expression in agonist-pretreated cells. The modulation of proinflammatory cytokine-evoked type II NOS expression by ATP and glutamate may play an important role in CNS pathologies associated with stroke and trauma.
authors.affiliation: Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: H L
authors.initials: HL
authors.lastname: Lin
authors.forename: S
authors.initials: S
authors.lastname: Murphy
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000201:enzymology*; D015153:Blotting, Western; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D018698:Glutamic Acid / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats
chemical_list: D004791:Enzyme Inhibitors; D016328:NF-kappa B; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C