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

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.

Keywords::

• NADPH
• glutathione
• GSH
• isocitrate dehydrogenase
• G6PD
• acute kidney injury

This paper was first published online on Early Online on 03 May 2011.