title: [Clinical application of urinary redox regulating protein, thioredoxin].
abstract: Thioredoxin (TRX) is a redox-regulating protein, induced in response to oxidative stress. The function of TRX in the urine is unknown. We show here that urinary TRX begin to increase within one hour and peaks within two hours after ischemia reperfusion of mice. Serum levels of TRX are not changed by the ischemia/reperfusion. In a time-dependent study of immunohistochemistry, TRX appears diffusely in the tubular cytosol in sham-operated mice. On the other hand, immediately after renal ischemia/reperfusion, TRX become to eccentrically-locate in the apical side of the tubular cytosol, and then TRX is detected only in the urinary lumen. In contrast, when we examine the immunolocalization of glutaredoxin, which is a member of the TRX superfamily, we find that the immunoreactivity is unchanged after renal ischemia/reperfusion. Northern blotting and in situ hybridization show that epithelial cells constitutively express TRX mRNA but neither expression levels nor distribution are altered by ischemia-reperfusion. An overexpression of hTRX in transgenic mice attenuates the reperfusion injury. These data suggests that TRX is produced in tubular cells in a steady state. The increase in the urine after ischemia-reperfusion is not mediated by a de novo induction of TRX mRNA but by a discharge of TRX protein from tubular epithelial cells. TRX is useful for the diagnosis of AKI in association with oxidative stress.
authors.affiliation: Division of Nephrology and Clinical Laboratories, University of Fukui Hospital, Yoshida-gun, Fukui-pref. 910-1193, Japan. kkasuno@hotmail.com
authors.forename: Kenji
authors.initials: K
authors.lastname: Kasuno
authors.forename: Hideki
authors.initials: H
authors.lastname: Kimura
authors.forename: Naoki
authors.initials: N
authors.lastname: Takahashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mikami
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Nobukawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Shigemi
authors.forename: Haruyoshi
authors.initials: H
authors.lastname: Yoshida
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis; D000818:Animals; D015415:Biomarkers; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology; D013879:Thioredoxins / Q000032:analysis / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D013879:Thioredoxins