Abstract
Ischemic reperfusion injuries such as acute renal failure, acute liver failure, stroke, and myocardial infarction are prevalent causes of morbidity and mortality. Kidney ischemic reperfusion injury is the leading cause of acute renal failure and dysfunction of transplanted kidneys. Although significant progress has been made in deciphering the factors that contribute to ischemic reperfusion injury, treatment options for these injuries remain scant. Identifying the molecules that contribute to ischemic reperfusion injury and can be therapeutically targeted will lead to development of new approaches for the treatment of such injuries. The expression of spermidine/spermine-N1-acetyltransferase increases in the kidneys subjected to ischemic reperfusion injury. Furthermore, inactivation of the spermidine/spermine-N1-acetyltransferase gene reduces the severity of kidney damage after ischemic reperfusion injury. Enhanced expression of spermidine/spermine-N1-acetyltransferase in cultured cells leads to DNA damage, cell cycle arrest, and disruption of cell matrix interactions. The aforementioned observations strongly suggest that enhanced polyamine back conversion plays an important role in the mediation of tissue damage in renal Ischemic reperfusion injury.
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Bonventre JV (1993) Mechanisms of ischemic acute renal failure. Kidney Int 43:1160–1178
Ambrosio G, Zweier JL, Duilio C, Kuppusamy P, Santoro G, Elia PP, Tritto I, Cirillo P, Condorelli M, Chiariello M et al (1993) Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow. J Biol Chem 268:18532–18541
Thadhani R, Pascual M, Bonventre JV (1996) Acute renal failure. N Engl J Med 334:1448–1460
Zahedi K, Wang Z, Barone S, Prada AE, Kelly CN, Casero RA, Yokota N, Porter CW, Rabb H, Soleimani M (2003) Expression of SSAT, a novel biomarker of tubular cell damage, increases in kidney ischemia-reperfusion injury. Am J Physiol Renal Physiol 284:F1046–F1055
Zahedi K, Lentsch AB, Okaya T, Barone S, Sakai N, Witte DP, Arend LJ, Alhonen L, Jell J, Janne J, Porter CW, Soleimani M (2009) Spermidine/spermine-N 1-acetyltransferase ablation protects against liver and kidney ischemia reperfusion injury in mice. Am J Physiol Gastrointest Liver Physiol 296:G899–G909
Zahedi K, Bissler JJ, Wang Z, Josyula A, Lu L, Diegelman P, Kisiel N, Porter CW, Soleimani M (2007) Spermidine/spermine N 1-acetyltransferase overexpression in kidney epithelial cells disrupts polyamine homeostasis, leads to DNA damage, and causes G2 arrest. Am J Physiol Cell Physiol 292:C1204–C1215
Wang Z, Zahedi K, Barone S, Tehrani K, Rabb H, Matlin K, Casero RA, Soleimani M (2004) Overexpression of SSAT in kidney cells recapitulates various phenotypic aspects of kidney ischemia-reperfusion injury. J Am Soc Nephrol 15:1844–1852
Burne MJ, Haq M, Matsuse H, Mohapatra S, Rabb H (2000) Genetic susceptibility to renal ischemia reperfusion injury revealedin a murine model. Transplantation 69:1023–1025
Wei Q, Wang MH, Dong Z (2005) Differential gender differences in ischemic and nephrotoxic acute renal failure. Am J Nephrol 25:491–499
Kim M, Kim N, D’Agati VD, Emala CW Sr, Lee HT (2007) Isoflurane mediates protection from renal ischemia-reperfusion injury via sphingosine kinase and sphingosine-1-phosphate-dependent pathways. Am J Physiol Renal Physiol 293:F1827–F1835
Lee HT, Kim M, Kim N, Billings FT 4th, D’Agati VD, Emala CW Sr (2007) Isoflurane protects against renal ischemia and reperfusion injury and modulates leukocyte infiltration in mice. Am J Physiol Renal Physiol 293:F713–F722
Delbridge MS, Shrestha BM, Raftery AT, El Nahas AM, Haylor JL (2007) The effect of body temperature in a rat model of renal ischemia-reperfusion injury. Transplant Proc 39:2983–2985
Acknowledgements
The authors would like to thank Dr. Debora L. Kramer, Ms. Paula Diegelman, and Ms. Sharon L. Barone for their help with this manuscript. This work was supported by National Institutes of Health Grant RO1DK62809, Veterans Administration Merrit Review Award, and funds from the Center on Genetics of Transport at the University of Cincinnati.
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Zahedi, K., Soleimani, M. (2011). Spermidine/Spermine-N1-Acetyltransferase in Kidney Ischemia Reperfusion Injury. In: Pegg, A., Casero, Jr., R. (eds) Polyamines. Methods in Molecular Biology, vol 720. Humana Press. https://doi.org/10.1007/978-1-61779-034-8_24
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DOI: https://doi.org/10.1007/978-1-61779-034-8_24
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