Role of poly(ADP-ribose) glycohydrolase in the development of inflammatory bowel disease in mice

Salvatore Cuzzocrea, Emanuela Mazzon, Tiziana Genovese, Concetta Crisafulli, Woo Kee Min, Rosanna Di Paola, Carmelo Muià, Jia He Li, Giuseppe Malleo, Weizhen Xu, Edmond Massuda, Emanuela Esposito, Jie Zhang, Zhao Qi Wang

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Poly(ADP-ribose) is synthesized from nicotinamide adenine dinucleotide (NAD) by poly(ADP-ribose) polymerase 1 (PARP-1) and degraded by poly(ADP-ribose) glycohydrolase (PARG). The aim of the present study was to examine the role of PARG in the development of experimental colitis. To address this question, we used an experimental model of colitis, induced by dinitrobenzene sulfonic acid (DNBS). Mice lacking the functional 110-kDa isoform of PARG (PARG110KO mice) were resistant to colon injury induced by DNBS. The mucosa of colon tissues showed reduction of myeloperoxidase activity and attenuated staining for intercellular adhesion molecule 1 and vascular cell adhesion molecule 1. Moreover, overproduction of proinflammatory factors TNF-α and IL-1β and activation of cell death signaling pathway, i.e., the FAS ligand, were inhibited in these mutant mice. Finally pharmacological treatment of WT mice with GPI 16552 and 18214, two novel PARG inhibitors, showed a significant protective effect in DNBS-induced colitis. These genetic and pharmacological studies demonstrate that PARG modulates the inflammatory response and tissue injury events associated with colitis and PARG may be considered as a novel target for pharmacological intervention for the pathogenesis.

Original languageEnglish
Pages (from-to)90-105
Number of pages16
JournalFree Radical Biology and Medicine
Volume42
Issue number1
DOIs
Publication statusPublished - Jan 1 2007

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Inflammatory Bowel Diseases
Dinitrobenzenes
Colitis
Sulfonic Acids
Pharmacology
Colon
Tissue
Poly Adenosine Diphosphate Ribose
Poly(ADP-ribose) Polymerases
Vascular Cell Adhesion Molecule-1
Wounds and Injuries
Cell death
Intercellular Adhesion Molecule-1
Interleukin-1
NAD
Peroxidase
poly ADP-ribose glycohydrolase
Protein Isoforms
Mucous Membrane
Cell Death

Keywords

  • Apoptosis
  • Colitis
  • IL-1β
  • Inflammation
  • PARG inhibitor
  • PARG110 deletion
  • TNF-α

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Role of poly(ADP-ribose) glycohydrolase in the development of inflammatory bowel disease in mice. / Cuzzocrea, Salvatore; Mazzon, Emanuela; Genovese, Tiziana; Crisafulli, Concetta; Min, Woo Kee; Di Paola, Rosanna; Muià, Carmelo; Li, Jia He; Malleo, Giuseppe; Xu, Weizhen; Massuda, Edmond; Esposito, Emanuela; Zhang, Jie; Wang, Zhao Qi.

In: Free Radical Biology and Medicine, Vol. 42, No. 1, 01.01.2007, p. 90-105.

Research output: Contribution to journalArticle

Cuzzocrea, S, Mazzon, E, Genovese, T, Crisafulli, C, Min, WK, Di Paola, R, Muià, C, Li, JH, Malleo, G, Xu, W, Massuda, E, Esposito, E, Zhang, J & Wang, ZQ 2007, 'Role of poly(ADP-ribose) glycohydrolase in the development of inflammatory bowel disease in mice', Free Radical Biology and Medicine, vol. 42, no. 1, pp. 90-105. https://doi.org/10.1016/j.freeradbiomed.2006.09.025
Cuzzocrea, Salvatore ; Mazzon, Emanuela ; Genovese, Tiziana ; Crisafulli, Concetta ; Min, Woo Kee ; Di Paola, Rosanna ; Muià, Carmelo ; Li, Jia He ; Malleo, Giuseppe ; Xu, Weizhen ; Massuda, Edmond ; Esposito, Emanuela ; Zhang, Jie ; Wang, Zhao Qi. / Role of poly(ADP-ribose) glycohydrolase in the development of inflammatory bowel disease in mice. In: Free Radical Biology and Medicine. 2007 ; Vol. 42, No. 1. pp. 90-105.
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