| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Division of Nephrology and Hypertension, Department of Pediatrics, Children's Hospital Medical Center, 2 Division of Nephrology and Hypertension, Department of Medicine, University of Cincinnati, and 6 Veterans Affairs Medical Center, Cincinnati, Ohio 45267; 4 Division of Nephrology, Department of Medicine, and 3 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21218; and 5 Roswell Park Cancer Institute, Buffalo, New York 14263
Ischemia-reperfusion injury (IRI) is the major cause of acute renal failure in native and allograft kidneys. Identifying the molecules and pathways involved in the pathophysiology of renal IRI will yield valuable new diagnostic and therapeutic information. To identify differentially regulated genes in renal IRI, RNA from rat kidneys subjected to an established renal IRI protocol (bilateral occlusion of renal pedicles for 30 min followed by reperfusion) and time-matched kidneys from sham-operated animals was subjected to suppression subtractive hybridization. The level of spermidine/spermine N1-acetyltransferase (SSAT) mRNA, an essential enzyme for the catabolism of polyamines, increased in renal IRI. SSAT expression was found throughout normal kidney tubules, as detected by nephron segment RT-PCR. Northern blots demonstrated that the mRNA levels of SSAT are increased by greater than threefold in the renal cortex and by fivefold in the renal medulla at 12 h and returned to baseline at 48 h after ischemia. The increase in SSAT mRNA was paralleled by an increase in SSAT protein levels as determined by Western blot analysis. The concentration of putrescine in the kidney increased by ~4- and ~7.5-fold at 12 and 24 h of reperfusion, respectively, consistent with increased functional activity of SSAT. To assess the specificity of SSAT for tubular injury, a model of acute renal failure from Na+ depletion (without tubular injury) was studied; SSAT mRNA levels remained unchanged in rats subjected to Na+ depletion. To distinguish SSAT increases from the effects of tubular injury vs. uremic toxins, SSAT was increased in cis-platinum-treated animals before the onset of renal failure. The expression of SSAT mRNA and protein increased by ~3.5- and >10-fold, respectively, in renal tubule epithelial cells subjected to ATP depletion and metabolic poisoning (an in vitro model of kidney IRI). Our results suggest that SSAT is likely a new marker of tubular cell injury that distinguishes acute prerenal from intrarenal failure.
acute renal failure; polyamines; putrescine; spermidine/spermine N1-acetyltransferase
This article has been cited by other articles:
|
|
 |
|
  K. Zahedi, A. B. Lentsch, T. Okaya, S. Barone, N. Sakai, D. P. Witte, L. J. Arend, L. Alhonen, J. Jell, J. Janne, et al. Spermidine/spermine-N1-acetyltransferase ablation protects against liver and kidney ischemia-reperfusion injury in mice Am J Physiol Gastrointest Liver Physiol, April 1, 2009; 296(4): G899 - G909. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Pegg Spermidine/spermine-N1-acetyltransferase: a key metabolic regulator Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E995 - E1010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Venkataraman and J. A. Kellum Defining Acute Renal Failure: The RIFLE Criteria J Intensive Care Med, July 1, 2007; 22(4): 187 - 193. [Abstract] [PDF]
|
|
|
|
 |
|
 K. Zahedi, J. J. Bissler, Z. Wang, A. Josyula, L. Lu, P. Diegelman, N. Kisiel, C. W. Porter, and M. Soleimani Spermidine/spermine N1-acetyltransferase overexpression in kidney epithelial cells disrupts polyamine homeostasis, leads to DNA damage, and causes G2 arrest Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1204 - C1215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wang and R. A. Casero Jr. Mammalian Polyamine Catabolism: A Therapeutic Target, a Pathological Problem, or Both? J. Biochem., January 1, 2006; 139(1): 17 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Tomitori, T. Usui, N. Saeki, S. Ueda, H. Kase, K. Nishimura, K. Kashiwagi, and K. Igarashi Polyamine Oxidase and Acrolein as Novel Biochemical Markers for Diagnosis of Cerebral Stroke Stroke, December 1, 2005; 36(12): 2609 - 2613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Barone, T. Okaya, S. Rudich, S. Petrovic, K. Tenrani, Z. Wang, K. Zahedi, R. A. Casero, A. B. Lentsch, and M. Soleimani Distinct and sequential upregulation of genes regulating cell growth and cell cycle progression during hepatic ischemia-reperfusion injury Am J Physiol Cell Physiol, October 1, 2005; 289(4): C826 - C835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Wang, K. Zahedi, S. Barone, K. Tehrani, H. Rabb, K. Matlin, R. A. Casero, and M. Soleimani Overexpression of SSAT in Kidney Cells Recapitulates Various Phenotypic Aspects of Kidney Ischemia-reperfusion Injury J. Am. Soc. Nephrol., July 1, 2004; 15(7): 1844 - 1852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Zahedi, Z. Wang, S. Barone, K. Tehrani, N. Yokota, S. Petrovic, H. Rabb, and M. Soleimani Identification of stathmin as a novel marker of cell proliferation in the recovery phase of acute ischemic renal failure Am J Physiol Cell Physiol, May 1, 2004; 286(5): C1203 - C1211. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
