Abstract
Poly (ABP-ribosyl)ation, an early post-translational modification in response to DNA damage, is catalyzed by poly (ADP-ribose) polymerase (PARP-1) and caiabolized by poly(ABP-ribose) glycohydrolase (PARG). The aim of this study was to investigate the role of PARG on the modulation of the inflammatory response caused by splanchnic ischemia and reperfusion. SAO shock in rats and wild-type (WT) mice was associated with a significant neutrophil infiltration in the ileum and production of tumor necrosis factor-α (TNF-α). Reperfused ileum tissue sections from SAO-shocked WT mice and rats showed positive staining for P-selectin and ICAM-1 localized mainly in the vascular endothelial cells. Genetic disruption of the PARG gene in mice or pharmacological inhibition of PARG by PARG inhibitors significantly improved the histological status of the reperfused tissues associated with reduced expression of P-selectin and ICAM-1, neutrophil infiltration into the reperfused intestine, and TNF-α production. These results suggest that PARG activity modulates the inflammatory response in ischemia/reperfusion and participates in end (target) organ damage under these conditions.
Original language | English (US) |
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Pages (from-to) | 558-566 |
Number of pages | 9 |
Journal | FASEB Journal |
Volume | 19 |
Issue number | 6 |
DOIs | |
State | Published - Apr 2005 |
Externally published | Yes |
Keywords
- Ischemia and reperfusion
- Neutrophil infiltration
- Organ injury
- PARG inhibitor
- SAO shock
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- General Biochemistry, Genetics and Molecular Biology
- Biochemistry
- Cell Biology