Expression of SSAT, a novel biomarker of tubular cell damage, increases in kidney ischemia-reperfusion injury

Kamyar Zahedi, Zhaohui Wang, Sharon Barone, Anne E. Prada, Caitlin N. Kelly, Robert A Casero, Naoko Yokota, Carl W. Porter, Hamid Rabb, Manoocher Soleimani

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Renal Physiology
Volume284
Issue number5 53-5
StatePublished - May 1 2003

Fingerprint

Spermine
Reperfusion Injury
Biomarkers
Kidney
Messenger RNA
Wounds and Injuries
Acute Kidney Injury
diamine N-acetyltransferase
Reperfusion
Kidney Tubules
Putrescine
Nephrons
Polyamines
Northern Blotting
Poisoning
Cisplatin
Renal Insufficiency
Allografts
Proteins
Ischemia

Keywords

  • Acute renal failure
  • Polyamines
  • Putrescine
  • Spermidine/spermine N-acetyltransferase

ASJC Scopus subject areas

  • Physiology

Cite this

Expression of SSAT, a novel biomarker of tubular cell damage, increases in kidney ischemia-reperfusion injury. / Zahedi, Kamyar; Wang, Zhaohui; Barone, Sharon; Prada, Anne E.; Kelly, Caitlin N.; Casero, Robert A; Yokota, Naoko; Porter, Carl W.; Rabb, Hamid; Soleimani, Manoocher.

In: American Journal of Physiology - Renal Physiology, Vol. 284, No. 5 53-5, 01.05.2003.

Research output: Contribution to journalArticle

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', American Journal of Physiology - Renal Physiology, vol. 284, no. 5 53-5.
Zahedi, Kamyar ; Wang, Zhaohui ; Barone, Sharon ; Prada, Anne E. ; Kelly, Caitlin N. ; Casero, Robert A ; Yokota, Naoko ; Porter, Carl W. ; Rabb, Hamid ; Soleimani, Manoocher. / Expression of SSAT, a novel biomarker of tubular cell damage, increases in kidney ischemia-reperfusion injury. In: American Journal of Physiology - Renal Physiology. 2003 ; Vol. 284, No. 5 53-5.
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AU - Wang, Zhaohui

AU - Barone, Sharon

AU - Prada, Anne E.

AU - Kelly, Caitlin N.

AU - Casero, Robert A

AU - Yokota, Naoko

AU - Porter, Carl W.

AU - Rabb, Hamid

AU - Soleimani, Manoocher

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