Poly(ADP-ribose) polymerase: a new therapeutic target?
OBJECTIVE
To overview the emerging data in the literature showing the role of poly(ADP-ribose) polymerase (PARP) in the pathogenesis of critical illness.


RESULTS
PARP, an abundant nuclear enzyme involved in DNA repair and transcriptional regulation, is now recognized as a key regulator of cell survival and cell death in response to noxious stimuli in various forms of cardiovascular collapse. PARP becomes activated in response to oxidative DNA damage and depletes cellular energy pools, thus leading to cellular dysfunction in various tissues. The activation of PARP may also induce various cell death processes, and promotes an inflammatory response. In circulatory shock PARP plays a crucial role both in the development of early cardiovascular dysfunction and in the delayed systemic inflammatory response syndrome with associated multiple organ failure. Inhibition of PARP activity is protective in various models of circulatory shock.


CONCLUSIONS
A solid body of literature supports the view that PARP is an important target for therapeutic intervention in critical illness.
Gerö
Domokos
D
CellScreen Applied Research Center, Semmelweis University Medical School, Budapest, Hungary.
Szabó
Csaba
C
D000818:Animals; D016638:Critical Illness; D004730:Endothelium, Vascular / Q000503:physiopathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology; D008168:Lung / Q000378:metabolism; D009102:Multiple Organ Failure / Q000209:etiology; D010539:Permeability; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology; D014661:Vasoconstriction
D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases