Aggravation of ischemia-reperfusion-triggered acute renal failure in xCT-deficient mice.
This study examined the question of whether deficiency of xCT, a cystine-transporter gene, exacerbates ischemia-reperfusion-induced acute renal failure (ARF). Two weeks after the right nephrectomy of male mice at 16-18weeks of age, the left renal vessels were clamped for 45min to induce renal ischemia. After (24h) induction of ischemia, xCT(-/-) mice had elevated concentrations of blood urea nitrogen and creatinine indicative of ARF, while in xCT(+/-) and xCT(+/+) mice, these parameters did not differ from the sham-operated mice. Immunohistochemical analyses of kidneys using antibodies against the oxidative stress markers revealed stronger staining in xCT(-/-) mice compared with xCT(+/+) mice. Induction of xCT mRNA in the kidneys of xCT(+/+) mice was demonstrated using reverse transcriptase (RT)-PCR analysis and was further confirmed using quantitative RT-PCR. These data provide the first in vivo evidence that xCT is induced by oxidative stress and helps prevent ischemia-reperfusion injury to kidneys.
Shibasaki
Tomohiro
T
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Japan.
Iuchi
Yoshihito
Y
Okada
Futoshi
F
Kuwata
Kazuho
K
Yamanobe
Takuya
T
Bannai
Shiro
S
Tomita
Yoshihiko
Y
Sato
Hideyo
H
Fujii
Junichi
J
D058186:Acute Kidney Injury / Q000378:metabolism*; D027182:Amino Acid Transport System y+ / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D003433:Crosses, Genetic; D007150:Immunohistochemistry; D007511:Ischemia / Q000209:etiology / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009392:Nephrectomy; D015424:Reperfusion / Q000009:adverse effects; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control*
D027182:Amino Acid Transport System y+; C492255:Slc7a11 protein, mouse; D003404:Creatinine