التفاصيل البيبلوغرافية
| العنوان: |
Resistance to endotoxic shock as a consequence of defective NF-?B activation in poly (ADP-ribose) polymerase-1 deficient mice. |
| المؤلفون: |
Oliver, F. Javier, Ménissier-de Murcia, Josianne, Nacci, Carmela, Decker, Patrice, Andriantsitohaina, Ramaroson, Muller, Sylviane, de la Rubia, Guadalupe, Stoclet, Jean Claude, de Murcia, Gilbert |
| المصدر: |
EMBO Journal; 8/15/99, Vol. 18 Issue 16, p4446-4454, 9p |
| مصطلحات موضوعية: |
SEPTIC shock, NF-kappa B, NITRIC oxide, DNA polymerases, DNA ligases, GENETIC transcription, TUMOR necrosis factors, ENDOTOXINS |
| مستخلص: |
Poly (ADP-ribose) polymerase-1 is a nuclear DNA-binding protein that participates in the DNA base excision repair pathway in response to genotoxic stress in mammalian cells. Here we show that PARP-1-deficient cells are defective in NF-κB-dependent transcription activation, but not in its nuclear translocation, in response to TNF-α. Treating mice with lipopolysaccharide (LPS) resulted in the rapid activation of NF-κB in macrophages from PARP-1+/+ but not from PARP-1-/- mice. PARP-1-deficient mice were extremely resistant to LPS-induced endotoxic shock. The molecular basis for this resistance relies on an almost complete abrogation of NF-·B-dependent accumulation of TNF-α in the serum and a down-regulation of inducible nitric oxide synthase (iNOS), leading to decreased NO synthesis, which is the main source of free radical generation during inflammation. These results demonstrate a functional association in vivo between PARP-1 and NF-κB, with consequences for the transcriptional activation of NF-κB and a systemic inflammatory process. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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