title: Delayed preconditioning by sevoflurane elicits changes in the mitochondrial proteome in ischemia-reperfused rat hearts.
abstract: BACKGROUND
  Delayed myocardial preconditioning by volatile anesthetics involves changes in DNA transcription and translation. Mitochondria play a central role in myocardial ischemia/reperfusion (I/R) injury and in ischemic or pharmacologic preconditioning. In this study, we investigated whether there are alterations in myocardial mitochondrial protein expression after volatile anesthetic preconditioning (APC) to examine the underlying mechanisms of delayed cardioprotection.
  
  
  METHODS
  Thirty-six Sprague-Dawley rats were randomly assigned to 1 of 3 groups (n = 12 for each group). Rats in the delayed APC group were exposed to sevoflurane (2.5% for 60 minutes) 24 hours before myocardial ischemia was induced. Myocardial ischemia in the I/R and APC groups was induced by left coronary artery occlusion for 30 minutes, followed by 120 minutes of reperfusion. The control group received no treatment. The mitochondria fractions were prepared by differential centrifugation with density gradient isolation for proteomic analysis. Two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry was used to identify differences in the protein expression from mitochondria of the rat hearts.
  
  
  RESULTS
  Fifteen differentially expressed mitochondrial proteins between the APC group and I/R group were identified and the expression patterns of 2 of the proteins were confirmed by Western blot analysis. These proteins were associated with mitochondrial substrate metabolism, respiration, and adenosine triphosphate (ATP)/adenosine diphosphate transport. The modifications of the mitochondrial proteome suggest an enhanced capacity of mitochondria to maintain myocardial ATP levels after I/R injury.
  
  
  CONCLUSIONS
  Delayed sevoflurane myocardial preconditioning induces mitochondrial proteome remodeling, which mainly involves proteins that are related to ATP generation and transport. Therefore, proteomic changes related to bioenergetic balance may be the mechanistic basis of delayed anesthetic myocardial preconditioning.
authors.affiliation: Department of Anesthesiology, Second Xiang-Ya Hospital, Central South University, No. 139, Ren-Min Rd., Changsha, Hunan Province, China.
authors.forename: Yan-Ying
authors.initials: YY
authors.lastname: Xiao
authors.forename: Ye-Tian
authors.initials: YT
authors.lastname: Chang
authors.forename: Ke
authors.initials: K
authors.lastname: Ran
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Liu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D020543:Proteome / Q000187:drug effects; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics* / Q000503:physiopathology; D000077149:Sevoflurane; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D019210:Troponin I / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D024101:Mitochondrial Proteins; D020543:Proteome; D019210:Troponin I; D000077149:Sevoflurane; D000255:Adenosine Triphosphate