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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
- Source :
- Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 27(10)
- Publication Year :
- 2012
-
Abstract
- 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.
- Subjects :
- Male
medicine.medical_specialty
Ischemia
bcl-X Protein
Apoptosis
Kidney
Wortmannin
chemistry.chemical_compound
Mice
Internal medicine
medicine
Animals
Ischemic Preconditioning
Protein kinase B
Phosphoinositide-3 Kinase Inhibitors
Transplantation
Mice, Inbred BALB C
Renal ischemia
business.industry
Kidney metabolism
medicine.disease
Androstadienes
medicine.anatomical_structure
Endocrinology
Kidney Tubules
chemistry
Proto-Oncogene Proteins c-bcl-2
Nephrology
Reperfusion Injury
Immunology
Ischemic preconditioning
bcl-Associated Death Protein
business
Reperfusion injury
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 14602385
- Volume :
- 27
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
- Accession number :
- edsair.doi.dedup.....25b69f67e73fc2297ab2712cb2c82957