title: The role of macrophage migration inhibitory factor in anesthetic-induced myocardial preconditioning.
abstract: BACKGROUND
  Anesthetic-induced preconditioning (AIP) is known to elicit cardioprotective effects that are mediated at least in part by activation of the kinases AMPK and PKCε as well as by inhibition of JNK. Recent data demonstrated that the pleiotropic cytokine macrophage migration inhibitory factor (MIF) provides cardioprotection through activation and/or inhibition of kinases that are also known to mediate effects of AIP. Therefore, we hypothesized that MIF could play a key role in the AIP response.
  
  
  METHODS
  Cardiomyocytes were isolated from rats and subjected to isoflurane preconditioning (4 h; 1.5 vol. %). Subsequently, MIF secretion and alterations in the activation levels of protective kinases were compared to a control group that was exposed to ambient air conditions. MIF secretion was quantified by ELISA and AIP-induced activation of protein kinases was assessed by Western blotting of cardiomyocyte lysates after isoflurane treatment.
  
  
  RESULTS
  In cardiomyocytes, preconditioning with isoflurane resulted in a significantly elevated secretion of MIF that followed a biphasic behavior (30 min vs. baseline: p = 0.020; 24 h vs. baseline p = 0.000). Moreover, quantitative polymerase chain reaction demonstrated a significant increase in MIF mRNA expression 8 h after AIP. Of note, activation of AMPK and PKCε coincided with the observed peaks in MIF secretion and differed significantly from baseline.
  
  
  CONCLUSIONS
  These results suggest that the pleiotropic mediator MIF is involved in anesthetic-induced preconditioning of cardiomyocytes through stimulation of the protective kinases AMPK and PKCε.
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, University Hospital, RWTH Aachen, Aachen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Goetzenich
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, University Hospital, RWTH Aachen, Aachen, Germany; Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kraemer
authors.affiliation: Department of Anesthesiology, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Rossaint
authors.affiliation: Department of Anesthesiology, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bleilevens
authors.affiliation: Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Dollo
authors.affiliation: Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Siry
authors.affiliation: Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Setareh
authors.initials: S
authors.lastname: Rajabi-Alampour
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, University Hospital, RWTH Aachen, Aachen, Germany; Department of Anesthesiology, University Hospital of the RWTH Aachen, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Beckers
authors.affiliation: Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Josefin
authors.initials: J
authors.lastname: Soppert
authors.affiliation: Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Hongqi
authors.initials: H
authors.lastname: Lue
authors.affiliation: Department of Anesthesiology and Cardiovascular Science, University Hospitals Gasthuisberg, KU Leuven, Leuven, Belgium.
authors.forename: Steffen
authors.initials: S
authors.lastname: Rex
authors.affiliation: Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bernhagen
authors.affiliation: Department of Thoracic, Cardiac and Vascular Surgery, University Hospital, RWTH Aachen, Aachen, Germany; Institute of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Stoppe
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D007530:Isoflurane / Q000494:pharmacology*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018685:Anesthetics, Inhalation; D002316:Cardiotonic Agents; D008263:Macrophage Migration-Inhibitory Factors; D009124:Muscle Proteins; D007530:Isoflurane; D011494:Protein Kinases; D019746:Intramolecular Oxidoreductases; C515599:Mif protein, rat