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- Title
The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-κB in inflammatory disorders.
- Authors
Hassa, P. O.; Hottiger, M. O.
- Abstract
Mammalian poly(ADP-ribose)polymerase 1 (PARP-1) is an abundant nuclear chromatin-associated protein and belongs to a large family of enzymes that catalyzes the transfer of ADP-ribose units from its substrate β-nicotinamide adenine dinucleotide (NAD+) covalently to itself and other nuclear chromatin-associated proteins. PARP-1 knockout mice are protected against myocardial infarction, streptozotocin-induced diabetes, lipopolysaccharide-induced septic shock, and zymosan-induced multiple organ failure, indicating that PARP-1 is involved in the regulation of the pathogenesis of these disorders. PARP-1 and nuclear factor kappa B (NF-κB) have both been suggested to play a crucial role in inflammatory disorders. NF-κB encompasses a family of inducible transcription factors which play a crucial role in the regulation of genes involved in immune and inflammatory responses. Recent reports have shown that PARP-1 can act as a coactivator of NF-κB. These findings might provide new insights into the pathophysiology of different diseases such as type I diabetes and septic shock. The purpose of this review is to give a short overview of the current knowledge about PARP-1 and its functional and biochemical interactions with NF-κB. A more precise role for PARP-1 in NF-κB-dependent gene regulation and cellular metabolism during development of pathophysiological processes is discussed. Special considerations is given to the pathophysiological significance of these findings in terms of inflammatory disorders.
- Subjects
ADENOSINE diphosphate; RIBOSE; NF-kappa B; NAD (Coenzyme); LABORATORY mice
- Publication
Cellular & Molecular Life Sciences, 2002, Vol 59, Issue 9, p1534
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-002-8527-2