title: Protective roles of thioredoxin, a redox-regulating protein, in renal ischemia/reperfusion injury.
abstract: BACKGROUND
  Thioredoxin (TRX) is a small protein with redox-regulating functions. Although TRX is known to be induced in response to various forms of oxidative stress, including ischemia/reperfusion injury, the induction and the specific role of this protein in the kidney have not been fully investigated.
  
  
  METHODS
  Renal ischemia/reperfusion was induced by the clipping and release of renal arteries in C57BL/6 and human thioredoxin-overexpressing transgenic (hTRX-Tg) mice. TRX protein was detected by immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay (ELISA). TRX mRNA was detected by in situ hybridization and Northern blotting. Renal functions were evaluated by measuring the levels of blood urea nitrogen and serum creatinine in these mice.
  
  
  RESULTS
  With ischemia/reperfusion, endogenous murine TRX was rapidly depleted from the cytosol in the cortical proximal tubuli and detected in the urinary lumen, whereas it was spread diffusely in all segments of the tubular epithelial cells in sham-operated mice. The urinary excretion of TRX increased transiently after ischemia/reperfusion and recovered to the control level in 72 hours. In the medullary thick ascending limb (mTAL), however, TRX was specifically retained in the cytosol. A similar distribution change of transgenic hTRX was observed in the kidney of hTRX-Tg. These hTRX-Tg mice were more resistant to the injury to the mTAL and functional deterioration caused by ischemia/reperfusion, compared with wild-type mice.
  
  
  CONCLUSIONS
  The present findings suggest that TRX is retained in mTAL and secreted from proximal tubuli into urine during renal ischemia/reperfusion. The mTAL-specific retention of TRX may have a protective effect against renal ischemia/reperfusion injury.
authors.affiliation: Department of Biological Responses, Institute for Virus Research, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kasuno
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Takahiko
authors.initials: T
authors.lastname: Ono
authors.forename: Eri
authors.initials: E
authors.lastname: Muso
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
mesh_terms: D000818:Animals; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D013879:Thioredoxins