Submitted on August 22, 2008
Revised on December 29, 2008
Accepted on January 12, 2009
Spermidine/Spermine-N1-acetyltransferase Ablation Protects Against Liver and Kidney Ischemia Reperfusion Injury in Mice+
Kamyar Zahedi1, Alex B. Lentsch2, Tomohisa Okaya1, Sharon L Barone1, Nozomu Sakai2, David P Witte3, Lois J. Arend2, Leena Alhonen4, Jason Jell5, Juhani Janne4, Carl W. Porter6, and Manoocher Soleimani1*
1 University of Cincinnati College of Medicine
2 University of Cincinnati
3 Children's Hospital Medical Center
4 University of Kuopio
5 Roswell Park Cancer Institute
6 Roswell Park Cancer Inst
* To whom correspondence should be addressed. E-mail: manoocher.soleimani{at}uc.edu.
Expression of spermine/spermidine-N1-acetyltransferase (SSAT), the rate-limiting enzyme of polyamine back conversion cascade, increases after ischemia reperfusion injuries (IRI). We hypothesized that SSAT plays an important role in the mediation of IRI. In order 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 back-conversion is not functional in SSAT-deficient mice. When subjected to hepatic IRI, SSAT-ko mice were significantly protected against liver damage compared to SSAT-wt mice. Similarly, SSAT-ko animals subjected to renal IRI showed significant protection against damage to kidney tubules when compared to similarly treated 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.
