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 16–18 weeks of age, the left renal vessels were clamped for 45 min to induce renal ischemia. After (24 h) 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.