Role of N-acetyl-N-nitroso-tryptophan as nitric oxide donor in the modulation of HIF-1-dependent signaling
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Utta Berchner-Pfannschmidt
Abstract
N-Acetyl-N-nitroso-tryptophan (NANT) is well known for its capacity to generate nitric oxide (NO)-releasing compounds. It is unknown, however, whether NANT can be successfully applied as a precursor of NO in a complex biological environment such as a cell culture system. NO donors can be useful to induce the transcription factor hypoxia-inducible factor 1 (HIF-1) that coordinates the protection of cells and tissues from the lack of oxygen, termed hypoxia. HIF-1 degradation is controlled by prolyl hydroxylase 2 (PHD2) which needs to be inhibited for HIF-1 accumulation. Here, the effects of NANT in inhibiting recombinant PHD2 and up-regulating of HIF-1 and HIF-1-mediated carboanhydrase-9 (CA9) mRNA expression were compared in living cells with the NO donors N-nitrosomelatonin (NOMela) and S-nitrosoglutathione (GSNO) under normoxic and hypoxic conditions. In contrast to GSNO, NANT was similar to NOMela being highly effective in inhibiting recombinant PHD2. NANT-mediated activation of HIF-1 in oxygenated cells was comparable to hypoxic activation of HIF-1 in all cases. In contrast, under hypoxia NANT was able to boost hypoxic cellular HIF-1 levels by further reducing the activity of cellular PHD2. The strong increase of HIF-dependent CA9 mRNA expression demonstrated that NANT-induced HIF-1 was transcriptionally active. Finally, the efficacy of NANT to increase both HIF-1 and CA9 mRNA did not depend on the absolute conformation of the tryptophan moiety. In conclusion, NANT appears to be an excellent NO donor for cells in culture and l-NANT should be useful for in vivo animal studies.
©2010 by Walter de Gruyter Berlin New York
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Artikel in diesem Heft
- REVIEW
- Chaperone-assisted degradation: multiple paths to destruction
- MINIREVIEWS
- Principles, implementation, and application of biology-oriented synthesis (BIOS)
- The molecular biology of moenomycins: towards novel antibiotics based on inhibition of bacterial peptidoglycan glycosyltransferases
- Kallikrein-related peptidase genes as promising biomarkers for prognosis and monitoring of human malignancies
- GENES AND NUCLEIC ACIDS
- Zinc supplement greatly improves the condition of parkin mutant Drosophila
- MOLECULAR MEDICINE
- Differential role of cathepsins B and L in autophagy-associated cell death induced by arsenic trioxide in U87 human glioblastoma cells
- CELL BIOLOGY AND SIGNALING
- Role of N-acetyl-N-nitroso-tryptophan as nitric oxide donor in the modulation of HIF-1-dependent signaling
- The role of salivary histatin and the human cathelicidin LL-37 in wound healing and innate immunity
- PROTEOLYSIS
- Detection and in-cell selectivity profiling of the full-length West Nile virus NS2B/NS3 serine protease using membrane-anchored fluorescent substrates
- Plasminogen hydrolysis by cathepsin S and identification of derived peptides as selective substrate for cathepsin V and cathepsin L inhibitor
- Expression and activity profiling of selected cysteine cathepsins and matrix metalloproteinases in synovial fluids from patients with rheumatoid arthritis and osteoarthritis
- Interdependence of kallikrein-related peptidases in proteolytic networks
