SearchPublisher and Institutes
You are here: Home :: Area NEM :: Life sciences :: Biochemistry
K.-D. Kröncke
Nitrosative Stress and Transcription
Low NO concentrations synthesized by constitutively expressed NO synthases act on several signaling pathways activating transcription factors (TF), such as NF-?B 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 redoxsensitive TF like NF-?B, AP-1, Oct-1, c-Myb, or zinc fingercontaining 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-?B), 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-?B or AP-1-dependent transcription, while in activated cells nitrosative stress rather abolishes NF-?B 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.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 384, 11/2003
Pages: 1365 - 1377