HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/G899    most recent 90507.2008v1 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 Google Scholar Google Scholar Articles by Zahedi, K. Articles by Soleimani, M. Search for Related Content PubMed PubMed Citation Articles by Zahedi, K. Articles by Soleimani, M.

LIVER AND BILIARY TRACT

Spermidine/spermine-N¹-acetyltransferase ablation protects against liver and kidney ischemia-reperfusion injury in mice

Kamyar Zahedi,¹ Alex B. Lentsch,² Tomohisa Okaya,² Sharon Barone,¹ Nozomu Sakai,² David P. Witte,³ Lois J. Arend,⁴ Leena Alhonen,⁵ Jason Jell,⁶ Juhani Jänne,^5, Carl W. Porter,⁶ and Manoocher Soleimani^1,7

¹Division of Nephrology and Hypertension and ²Department of Surgery, University of Cincinnati College of Medicine, Cincinnati; ³Division of Pathology, Children's Hospital Medical Center, Cincinnati; ⁴Division of Pathology, University of Cincinnati College of Medicine, Cincinnati; ⁵A. I. Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland; ⁶Roswell Park Cancer Institute, Buffalo, New York; and ⁷Veterans Affairs Medical Center, Cincinnati, Ohio

Submitted 22 August 2008 ; accepted in final form 12 January 2009

Expression of spermine/spermidine-N¹-acetyltransferase (SSAT), the rate-limiting enzyme of polyamine backconversion cascade, increases after ischemia-reperfusion injuries (IRI). We hypothesized that SSAT plays an important role in the mediation of IRI. To test our hypothesis, wild-type (SSAT-wt) and SSAT-deficient (SSAT-ko) mice were subjected to liver or kidney IRI by ligation of hepatic or renal arteries. The liver and kidney content of putrescine (Put), a downstream by-product of SSAT activity, increased in SSAT-wt animals but not in SSAT-ko animals after IRI, indicating that polyamine backconversion is not functional in SSAT-deficient mice. When subjected to hepatic IRI, SSAT-ko mice were significantly protected against liver damage compared with SSAT-wt mice. Similarly, SSAT-ko animals subjected to renal IRI showed significantly greater protection against damage to kidney tubules than SSAT-wt mice. These studies indicate that SSAT-deficient animals are protected against IRI and suggest that SSAT is an important mediator of the tissue damage in IRI.

polyamine catabolism; polyamine backconversion; acute liver failure; acute kidney injury