Role of poly(ADP-ribose) glycohydrolase (PARG) in shock, ischemia and reperfusion.
Poly(ADP-ribosyl)ation is regulated by the synthesizing enzyme poly(ADP-ribose) polymerase-1 (PARP-1) and the degrading enzyme poly(ADP-ribose) glycohydrolase (PARG). Homeostasis of poly(ADP-ribosyl)ation has been proposed to be an important regulator for pathogenesis in multi-cellular organisms. Although the role of PARP-1 in tissue damage, inflammation and ischemia has been extensively studied, the function of PARG in various cellular processes is largely unknown. Recent studies using chemical inhibitors of PARG and genetically engineered Drosophila and mouse models that carry a disrupted PARG gene have started to shed new light on the biological function of PARG in vivo. These animal models and cells isolated from them will be useful for further validation of PARG as a potential pharmaceutical target to intervene the pathogenesis induced by acute tissue injury, ischemia and inflammation.
Cuzzocrea
Salvatore
S
Department of Clinical and Experimental Medicine and Pharmacology, Torre Biologica, Policlinico Universitario, Via C. Valeria, Gazzi, 98123 Messina, Italy. salvator@unime.it
Wang
Zhao-Qi
ZQ
D000818:Animals; D002545:Brain Ischemia / Q000209:etiology; D004249:DNA Damage; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007511:Ischemia / Q000201:enzymology / Q000209:etiology*; D009102:Multiple Organ Failure / Q000209:etiology; D015427:Reperfusion Injury / Q000201:enzymology / Q000209:etiology*; D012772:Shock, Septic / Q000201:enzymology / Q000209:etiology*
D004791:Enzyme Inhibitors; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase