Spermidine/Spermine-N1-Acetyltransferase in Kidney Ischemia Reperfusion Injury
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.
Key wordsIschemic reperfusion injury Acute renal failure Spermidine/spermine-N1-acetyltransferase Polyamine back conversion
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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