Protective role of cytosolic NADP(+)-dependent isocitrate dehydrogenase, IDH1, in ischemic pre-conditioned kidney in mice

Free Radic Res. 2011 Jul;45(7):759-66. doi: 10.3109/10715762.2011.577426. Epub 2011 Apr 21.

Abstract

Ischemic pre-conditioning protects the kidney against subsequent ischemia/reperfusion (I/R). This study investigated the role of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDH1), a producer of NADPH, in the ischemic pre-conditioning. Mice were pre-conditioned by 30 min of renal ischemia and 8 days of reperfusion. In non-pre-conditioned mice 30 min of ischemia had significantly increased the levels of plasma creatinine, BUN, lipid peroxidation and hydrogen peroxide in kidneys, whereas in pre-conditioned mice, the ischemia did not increase them. The reductions of reduced glutathione and NADPH after I/R were greater in non-pre-conditioned mice than in pre-conditioned mice. Ischemic pre-conditioning prevented the I/R-induced decreases in IDH1 activity and expression, but not in glucose-6-phosphate dehydrogenase activity. In conclusion, protection of the kidney afforded by ischemic pre-conditioning may be associated with increased activity of IDH1 which relates to increased levels of NADPH, increased ratios of GSH/total glutathione, less oxidative stress and less kidney injury induced by subsequent I/R insult.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Urea Nitrogen
  • Creatinine / blood
  • Cytosol / enzymology
  • Glucosephosphate Dehydrogenase / metabolism
  • Glutathione / blood
  • Hydrogen Peroxide / blood
  • Ischemia / enzymology
  • Ischemic Preconditioning
  • Isocitrate Dehydrogenase / metabolism*
  • Kidney / blood supply
  • Kidney / enzymology*
  • Lipid Peroxidation
  • Mice
  • Mice, Inbred C57BL
  • NADP / metabolism
  • Oxidative Stress
  • Reperfusion Injury

Substances

  • NADP
  • Creatinine
  • Hydrogen Peroxide
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • Glucosephosphate Dehydrogenase
  • Glutathione