Shock, inflammation and PARP.
The activation of poly(ADP-ribose) polymerase (PARP) is well considered to play an important role in various patho-physiological conditions like inflammation and shock. A vast amount of circumstantial evidence implicates oxygen-derived free radicals (especially, superoxide and hydroxyl radical) and high-energy oxidants (such as peroxynitrite) as mediators of inflammation and shock. ROS (e.g., superoxide, peroxynitrite, hydroxyl radical and hydrogen peroxide) are all potential reactants capable of initiating DNA single strand breakage, with subsequent activation of the nuclear enzyme poly(ADP-ribose) synthetase (PARS), leading to eventual severe energy depletion of the cells, and necrotic-type cell death. During the last years, numerous experimental studies have clearly demonstrated the beneficial effects of PARP inhibition in cell cultures through rodent models and more recently in pre-clinical large animal models of acute and chronic inflammation. The aim of this review is to describe recent experimental evidence implicating PARP as a pathophysiological modulator of acute and chronic inflammation.
Cuzzocrea
Salvatore
S
Institute of Pharmacology, University of Messina, Torre Biologica, Policlinico Universitario Via C. Valeria, Gazzi, 98100 Messina, Italy. salvator@unime.it
D000818:Animals; D001168:Arthritis / Q000201:enzymology / Q000209:etiology; D001249:Asthma / Q000201:enzymology / Q000209:etiology; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000209:etiology*; D015212:Inflammatory Bowel Diseases / Q000201:enzymology / Q000209:etiology; D009102:Multiple Organ Failure / Q000201:enzymology / Q000209:etiology; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D012772:Shock, Septic / Q000201:enzymology / Q000209:etiology*
D011065:Poly(ADP-ribose) Polymerases