Cellular and Molecular Life Sciences CMLS

, Volume 59, Issue 9, pp 1534-1553

First online:

The functional role of poly(ADP-ribose)polymerase 1 as novel coactivator of NF-κB in inflammatory disorders

  • P. O. HassaAffiliated withInstitute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland), Fax + 41 1 635 68 40, e-mail: hottiger@vetbio.unizh.ch
  • , M. O. HottigerAffiliated withInstitute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland), Fax + 41 1 635 68 40, e-mail: hottiger@vetbio.unizh.ch

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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.

Key words. PARP-1; NF-κB; coactivator; positive cofactor; inflammatory response; endotoxin; septic shock; diabetes; peroxynitrite.