title: Nitrosative stress and transcription.
abstract: Low NO concentrations synthesized by constitutively expressed NO synthases act on several signaling pathways activating transcription factors (TF), such as NF-kappaB or AP-1, and thereby influence gene expression. In contrast, during inflammatory reactions the inducible NO synthase produces NO for prolonged periods of time. The resulting nitrosative stress directly affects redox-sensitive TF like NF-kappaB, AP-1, Oct-1, c-Myb, or zinc finger-containing TF, but also additional mechanisms have been identified. Nitrosative stress in some cases induces expression of TF (AP-1, p53), indirectly modulates activity or stability of TF (HIF-1, p53) or their inhibitors (NF-kappaB), or modulates accessibility of promoters via increased DNA methylation or histone deacetylation. Depending on the promoter the result is induced, increased, decreased or even totally inhibited expression of various target genes. In unstimulated cells nitrosative stress increases NF-kappaB- or AP-1-dependent transcription, while in activated cells nitrosative stress rather abolishes NF-kappaB- or AP-1-dependent transcription. Sometimes the oxygen concentration also is of prime importance, since under normoxic conditions nitrosative stress activates HIF-1-dependent transcription, while under hypoxic conditions nitrosative stress leads to inhibition of HIF-1-dependent transcription. This review summarizes what is known about effects of physiological NO levels as well as of nitrosative stress on transcription.
authors.affiliation: Institute of Molecular Medicine, Research Group Immunobiology, Medical Department, Heinrich-Heine-University Düsseldorf, D-20225 Düsseldorf, Germany.
authors.forename: Klaus-Dietrich
authors.initials: KD
authors.lastname: Kröncke
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007249:Inflammation / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D015538:Nitrosation; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000096:biosynthesis / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000502:physiology*; D016335:Zinc Fingers
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D009687:Nuclear Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D009569:Nitric Oxide; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III