Spermidine/spermine-N1-acetyltransferase ablation protects against liver and kidney ischemia-reperfusion injury in mice.
Expression of spermine/spermidine-N1-acetyltransferase (SSAT), the rate-limiting enzyme of polyamine backconversion cascade, increases after ischemia-reperfusion injuries (IRI). We hypothesized that SSAT plays an important role in the mediation of IRI. To test our hypothesis, wild-type (SSAT-wt) and SSAT-deficient (SSAT-ko) mice were subjected to liver or kidney IRI by ligation of hepatic or renal arteries. The liver and kidney content of putrescine (Put), a downstream by-product of SSAT activity, increased in SSAT-wt animals but not in SSAT-ko animals after IRI, indicating that polyamine backconversion is not functional in SSAT-deficient mice. When subjected to hepatic IRI, SSAT-ko mice were significantly protected against liver damage compared with SSAT-wt mice. Similarly, SSAT-ko animals subjected to renal IRI showed significantly greater protection against damage to kidney tubules than SSAT-wt mice. These studies indicate that SSAT-deficient animals are protected against IRI and suggest that SSAT is an important mediator of the tissue damage in IRI.
Zahedi
Kamyar
K
Division of Nephrology and Hypertension, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabine Way, MSB 259G, Cincinnati, OH 45267-0585, USA.
Lentsch
Alex B
AB
Okaya
Tomohisa
T
Barone
Sharon
S
Sakai
Nozomu
N
Witte
David P
DP
Arend
Lois J
LJ
Alhonen
Leena
L
Jell
Jason
J
Jänne
Juhani
J
Porter
Carl W
CW
Soleimani
Manoocher
M
D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000201:enzymology / Q000473:pathology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D011073:Polyamines / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D011073:Polyamines; D000099228:Diamine N-Acetyltransferase