Segment-specific overexpression of redoxins after renal ischemia and reperfusion: protective roles of glutaredoxin 2, peroxiredoxin 3, and peroxiredoxin 6

Free Radic Biol Med. 2011 Jul 15;51(2):552-61. doi: 10.1016/j.freeradbiomed.2011.04.036. Epub 2011 Apr 29.

Abstract

The disruption of redox control, i.e., oxidative stress, is one of the most destructive causes of ischemia-reperfusion (IR) injury. Thioredoxin (Trx) family proteins play a major role in the cellular response to oxidative stress. Here, we systematically investigated the levels and tissue distribution of 15 members of this family (Trx and TrxR 1 and 2, Nrx, Prx 1-6, and Grx 1-3 and 5) in mouse kidneys after induction of IR by comparing control, clamped, and contralateral organs. After IR, levels of various redoxins were quantified. Immunohistochemical analysis revealed segment-specific alterations induced by the ischemic insult. Grx2, Prx3, and Prx6 were highly expressed in proximal tubule cells. Overexpression of these proteins in HEK293 and HeLa cells subjected to hypoxia and reoxygenation revealed higher survival and proliferation rates and lower oxidative damage compared to controls. Furthermore, we report for the first time the accumulation of Grx1 at the apical side of distal convoluted cells and the specific secretion of Grx1 into the urine after IR. The differences in both the basal equipment and the segment-specific responses of the antioxidant proteins may contribute to the distinct susceptibilities and regeneration processes of the various segments of the nephron to the IR insult.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Western
  • DNA Primers
  • Glutaredoxins / physiology*
  • Kidney / blood supply*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peroxiredoxin VI / physiology*
  • Peroxiredoxins / physiology*
  • Reperfusion Injury / enzymology
  • Reperfusion Injury / prevention & control*

Substances

  • DNA Primers
  • Glutaredoxins
  • Peroxiredoxin VI
  • Peroxiredoxins