Journal Article

Previous ischemia and reperfusion injury results in resistance of the kidney against subsequent ischemia and reperfusion insult in mice; a role for the Akt signal pathway

Hee-Seong Jang, Jinu Kim, Ki Young Kim, Jee In Kim, Min Hyun Cho and Kwon Moo Park

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 10, pages 3762-3770
Published in print October 2012 | ISSN: 0931-0509
Published online May 2012 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfs097
Previous ischemia and reperfusion injury results in resistance of the kidney against subsequent ischemia and reperfusion insult in mice; a role for the Akt signal pathway

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Background

Kidneys previously exposed to ischemia and reperfusion (I/R), pre-conditioned by I/R, are less susceptible to subsequent I/R injury. Here, we investigated the role for protein kinase B (Akt) survival signaling pathways including anti-apoptosis pathways in the reduced susceptibility of I/R-pre-conditioned kidneys.

Methods

Mice were exposed to either a single I/R pre-conditioning event (SIRPC, 30 min of bilateral renal ischemia followed by 8 days of reperfusion) or sham-operation (non-SIRPC) and then subjected to either 30 min of bilateral renal ischemia or sham-operation (sham). Some of the mice received intra-peritoneal administrations of wortmannin, which is an inhibitor of phosphatidylinositol-3 kinase, PI3K.

Results

Thirty minutes of bilateral renal ischemia in non-SIRPC mice induced a dramatic increase in plasma creatinine (PCr) levels, but this was not observed in the SIRPC mouse. Consistent with the PCr results, tubular damage and apoptotic tubular cell death were more severe in the non-SIRPC mouse kidney than in the SIRPC mice. SIRPC increased the levels of phosphorylated-Akt and -Bad expression as well as the ratio of Bcl-2 to Bax expression in the kidney. I/R resulted in greater increases of phosphorylated-Akt and -Bad, Bcl-xL and Bcl-2, but a lower level of increase of Bax, in the SIRPC mouse kidneys than those in the non-SIRPC-mouse kidneys. Treatment with wortmannin during the SIRPC period inhibited SIRPC-induced increase in phosphorylated-Akt and -Bad expressions and eliminated tolerance of SIRPC mice kidneys to I/R insult.

Conclusion

Ischemic pre-conditioning confers renal resistance to I/R-induced apoptosis via activation of the Akt signal pathway.

Keywords: acute kidney injury; Akt; apoptosis; ischemia and reperfusion; ischemic pre-conditioning

Journal Article.  5312 words.  Illustrated.

Subjects: Nephrology

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