title: The outcome of renal ischemia-reperfusion injury is unchanged in AMPK-β1 deficient mice.
abstract: OBJECTIVE
  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 β1 subunit and compared to wild type (WT) mice.
  
  
  RESULTS
  Basal expression of activated AMPK, phosphorylayed at αThr¹⁷², was markedly reduced by 96% in AMPK-β1⁻/⁻ mice. Acute renal ischaemia caused a 3.2-fold increase in α1-AMPK activity and a 2.5-fold increase in α2-AMPK activity (P<0.001) that was associated with an increase in AMPK phosphorylation of the AMPK-α 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-β1⁻/⁻ mice compared with WT. There was no difference, however, in the severity of renal IRI at 24-hours between AMPK-β1⁻/⁻ 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nephrology, Austin Health, Melbourne, Victoria, Australia. Peter.Mount@austin.org.au
authors.forename: Peter F
authors.initials: PF
authors.lastname: Mount
authors.forename: Kurt
authors.initials: K
authors.lastname: Gleich
authors.forename: Shanna
authors.initials: S
authors.lastname: Tam
authors.forename: Scott A
authors.initials: SA
authors.lastname: Fraser
authors.forename: Suet-Wan
authors.initials: SW
authors.lastname: Choy
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dwyer
authors.forename: Bo
authors.initials: B
authors.lastname: Lu
authors.forename: Bryce Van
authors.initials: BV
authors.lastname: Denderen
authors.forename: Günter
authors.initials: G
authors.lastname: Fingerle-Rowson
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Kemp
authors.forename: David A
authors.initials: DA
authors.lastname: Power
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D003404:Creatinine / Q000097:blood; D004789:Enzyme Activation; D007668:Kidney / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology* / Q000473:pathology*; D014508:Urea / Q000097:blood
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D014508:Urea; D003404:Creatinine; C554549:Prkab1 protein, mouse; C569522:Prkab2 protein, mouse; D055372:AMP-Activated Protein Kinases