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Nephrology - Physiology


The Outcome of Renal Ischemia-Reperfusion Injury Is Unchanged in AMPK-ß1 Deficient Mice
Published: Monday, January 09, 2012
Author: Peter F. Mount et al.

by Peter F. Mount, Kurt Gleich, Shanna Tam, Scott A. Fraser, Suet-Wan Choy, Karen M. Dwyer, Bo Lu, Bryce Van Denderen, Günter Fingerle-Rowson, Richard Bucala, Bruce E. Kemp, David A. Power

Aim

Activation of the master energy-regulator AMP-activated protein kinase (AMPK) in the heart reduces the severity of ischemia-reperfusion injury (IRI) but the role of AMPK in renal IRI is not known. The aim of this study was to determine whether activation of AMPK by acute renal ischemia influences the severity of renal IRI.

Methods

AMPK expression and activation and the severity of renal IRI was studied in mice lacking the AMPK ß1 subunit and compared to wild type (WT) mice.

Results

Basal expression of activated AMPK, phosphorylayed at aThr172, was markedly reduced by 96% in AMPK-ß1-/- mice. Acute renal ischaemia caused a 3.2-fold increase in a1-AMPK activity and a 2.5-fold increase in a2-AMPK activity (P<0.001) that was associated with an increase in AMPK phosphorylation of the AMPK-a subunit at Thr172 and Ser485, and increased inhibitory phosphorylation of the AMPK substrate acetyl-CoA carboxylase. After acute renal ischemia AMPK activity was reduced by 66% in AMPK-ß1-/- mice compared with WT. There was no difference, however, in the severity of renal IRI at 24-hours between AMPK-ß1-/- and WT mice, as measured by serum urea and creatinine and histological injury score. In the heart, macrophage migration inhibitory factor (MIF) released during IRI contributes to AMPK activation and protects from injury. In the kidney, however, no difference in AMPK activation by acute ischemia was observed between MIF-/- and WT mice. Compared with the heart, expression of the MIF receptor CD74 was found to be reduced in the kidney.

Conclusion

The failure of AMPK activation to influence the outcome of IRI in the kidney contrasts with what is reported in the heart. This difference might be due to a lack of effect of MIF on AMPK activation and lower CD74 expression in the kidney.

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