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.

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.

• Authors: Hee-Seong Jang, Jinu Kim, Ki Young Kim, Jee In Kim, Min Hyun Cho, Kwon Moo Park
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 27 Issue 10 Pg. 3762-70 (Oct 2012) ISSN: 1460-2385 [Electronic] England
• PMID: 22555250 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androstadienes
• Bad protein, mouse
• Bcl2l1 protein, mouse
• Phosphoinositide-3 Kinase Inhibitors
• Proto-Oncogene Proteins c-bcl-2
• bcl-Associated Death Protein
• bcl-X Protein
• Proto-Oncogene Proteins c-akt
• Wortmannin

Topics

• Androstadienes (pharmacology)
• Animals
• Apoptosis
• Ischemia (metabolism)
• Ischemic Preconditioning (methods)
• Kidney (blood supply, injuries, metabolism, pathology)
• Kidney Tubules (pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Phosphoinositide-3 Kinase Inhibitors
• Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Reperfusion Injury (metabolism, pathology, prevention & control)
• Signal Transduction (drug effects)
• Wortmannin
• bcl-Associated Death Protein (metabolism)
• bcl-X Protein (metabolism)