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

被引:66
作者
Zahedi, K
Wang, ZH
Barone, S
Prada, AE
Kelly, CN
Casero, RA
Yokota, N
Porter, CW
Rabb, H
Soleimani, M
机构
[1] Childrens Hosp, Med Ctr, Dept Pediat, Div Nephrol & Hypertens, Cincinnati, OH 45267 USA
[2] Univ Cincinnati, Dept Med, Div Nephrol & Hypertens, Cincinnati, OH 45267 USA
[3] Vet Affairs Med Ctr, Cincinnati, OH 45267 USA
[4] Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21218 USA
[5] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21218 USA
[6] Roswell Pk Canc Inst, Buffalo, NY 14263 USA
关键词
acute renal failure; polyamines; putrescine; spermidine/spermine; N(1)-acetyltransferase;
D O I
10.1152/ajprenal.00318.2002
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
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 N(1)- 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 similar to 4- and similar to 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 similar to 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.
引用
收藏
页码:F1046 / F1055
页数:10
相关论文
共 49 条
[1]   Correlation of polyamine and growth responses to N1,N11-diethylnorspermine in primary fetal fibroblasts derived from transgenic mice overexpressing spermidine/spermine N1-acetyltransferase [J].
Alhonen, L ;
Karppinen, A ;
Uusi-Oukari, M ;
Vujcic, S ;
Korhonen, VP ;
Halmekytö, M ;
Kramer, DL ;
Hines, R ;
Jänne, J ;
Porter, CW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (04) :1964-1969
[2]   Activation of polyamine catabolism in transgenic rats induces acute pancreatitis [J].
Alhonen, L ;
Parkkinen, JJ ;
Keinänen, T ;
Sinervirta, R ;
Herzig, KH ;
Jänne, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (15) :8290-8295
[3]   Polyamines are required for the initiation of rat liver regeneration [J].
Alhonen, L ;
Räsänen, TL ;
Sinervirta, R ;
Parkkinen, JJ ;
Korhonen, VP ;
Pietilä, M ;
Jänne, J .
BIOCHEMICAL JOURNAL, 2002, 362 :149-153
[4]  
AMBROSIO G, 1993, J BIOL CHEM, V268, P18532
[5]   Spermidine/spermine N1-acetyl transferase activity in rat brain following transient focal cerebral ischemia and reperfusion [J].
Babu, GN ;
Sailor, KA ;
Sun, DD ;
Dempsey, RJ .
NEUROSCIENCE LETTERS, 2001, 300 (01) :17-20
[6]   Different localization of spermidine spermine N-1-acetyltransferase and ornithine decarboxylase transcripts in the rat kidney [J].
Bettuzzi, S ;
Marinelli, M ;
Strocchi, P ;
Davalli, P ;
Cevolani, D ;
Corti, A .
FEBS LETTERS, 1995, 377 (03) :321-324
[7]   MECHANISMS OF ISCHEMIC ACUTE-RENAL-FAILURE [J].
BONVENTRE, JV .
KIDNEY INTERNATIONAL, 1993, 43 (05) :1160-1178
[8]   Heat stress ameliorates ATP depletion-induced sublethal injury in mouse proximal tubule cells [J].
Borkan, SC ;
Wang, YH ;
Lieberthal, W ;
Burke, PR ;
Schwartz, JH .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 1997, 272 (03) :F347-F355
[9]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[10]   Induction of spermidine/spermine N1-acetyltransferase in human cancer cells in response to increased production of reactive oxygen species [J].
Chopra, S ;
Wallace, HM .
BIOCHEMICAL PHARMACOLOGY, 1998, 55 (07) :1119-1123