2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2004080677v1 16/3/712    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Patel, N. S.A. Articles by Thiemermann, C. Search for Related Content PubMed PubMed Citation Articles by Patel, N. S.A. Articles by Thiemermann, C.

Mice Lacking the 110-kD Isoform of Poly(ADP-Ribose) Glycohydrolase Are Protected against Renal Ischemia/Reperfusion Injury

Nimesh S.A. Patel^*, Ulrich Cortes, Rosanna Di Poala, Emanuela Mazzon, Helder Mota-Filipe, Salvatore Cuzzocrea, Zhao-Qi Wang and Christoph Thiemermann^*

^* Centre for Experimental Medicine, Nephrology & Critical Care, William Harvey Research Institute, Queen Mary, University of London, United Kingdom; Unit of Gene-Environment Interactions, International Agency for Research on Cancer, Lyon, France; Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy; and Unit of Pharmacology and Pharmacotoxicology, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal

Address correspondence to: Prof. C. Thiemermann, Centre for Experimental Medicine, Nephrology & Critical Care, William Harvey Research Institute, Queen Mary, University of London, Charterhouse Square, London, EC1M 6BQ, UK. Phone: +44-0-20-7882-6118; Fax: +44-0-20-7251-1685; E-mail: c.thiemermann{at}qmul.ac.uk

The role of poly(ADP-ribose) (PAR) glycohydrolase (PARG) in the pathophysiology of renal ischemia/reperfusion (I/R) injury is not known. Poly(ADP-ribosyl)ation is rapidly stimulated in cells after DNA damage caused by the generation of reactive oxygen and nitrogen species during I/R. Continuous or excessive activation of poly(ADP-ribose) polymerase-1 produces extended chains of ADP-ribose on nuclear proteins and results in a substantial depletion of intracellular NAD⁺ and subsequently, ATP, leading to cellular dysfunction and, ultimately, cell death. The key enzyme involved in polymer turnover is PARG, which possesses mainly exoglycosidase activity but can remove olig(ADP-ribose) fragments via endoglycosidic cleavage. Thus, the aim of this study was to investigate whether the absence of PARG₁₁₀ reduced the renal dysfunction, injury, and inflammation caused by I/R of the mouse kidney. Here, the renal dysfunction and injury caused by I/R (bilateral renal artery occlusion [30 min] followed by reperfusion [24 h]) in mice lacking PARG₁₁₀, the major nuclear isoform of PARG, was investigated. The following markers of renal dysfunction and injury were measured: Plasma urea, creatinine, aspartate aminotransferase, and histology. The following markers of inflammation were also measured: Myeloperoxidase activity, malondialdehyde levels, and plasma nitrite/nitrate. The degree of renal injury and dysfunction caused by I/R was significantly reduced in PARG₁₁₀-deficient mice when compared with their wild-type littermates, and there were no differences in any of the biochemical parameters measured between sham-operated PARG₁₁₀^–/– mice and sham-operated wild-type littermates. Thus, it is proposed that endogenous PARG₁₁₀ plays a pivotal role in the pathophysiology of I/R injury of the kidney.

This article has been cited by other articles:

				N. Cartwright, O. Murch, S. K. McMaster, M. J. Paul-Clark, D. A. van Heel, B. Ryffel, V. F. J. Quesniaux, T. W. Evans, C. Thiemermann, and J. A. Mitchell Selective NOD1 Agonists Cause Shock and Organ Injury/Dysfunction In Vivo Am. J. Respir. Crit. Care Med., March 15, 2007; 175(6): 595 - 603. [Abstract] [Full Text] [PDF]

				S. Cuzzocrea, T. Genovese, E. Mazzon, C. Crisafulli, W. Min, R. Di Paola, C. Muia, J.-H. Li, E. Esposito, P. Bramanti, et al. Poly(ADP-Ribose) Glycohydrolase Activity Mediates Post-Traumatic Inflammatory Reaction after Experimental Spinal Cord Trauma J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 127 - 138. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673