title: Dystrophin is a possible end-target of ischemic preconditioning against cardiomyocyte oncosis during the early phase of reperfusion.
abstract: OBJECTIVE
  Dystrophin is a sarcolemmal membrane protein that prevents the myocyte from oncosis induced by physical stress. Because ischemic preconditioning (IPC) protects mitochondria and prevents oncosis during reperfusion, we hypothesized that dystrophin is an end-target of IPC distal to mitochondrial protection.
  
  
  RESULTS
  Isolated rat hearts were subjected to 30 min ischemia followed by reperfusion. IPC was introduced by 3 cycles of 5 min ischemia and 5 min reperfusion. The loss of sarcolemmal dystrophin and myocardial ATP during ischemia was comparable between the control and the IPC heart. Similar changes in sarcolemmal dystrophin and myocardial ATP were observed when the heart was treated with 2,4-dinitrophenol (DNP), an uncoupler of mitochondrial respiration, or oligomycin, an inhibitor of mitochondrial F1F0-ATPase. However, the IPC heart increased sarcolemmal dystrophin during reperfusion associated with an increase in tetramethylrhodamine ethylester (TMRE) uptake, an indicator of mitochondrial membrane potential (DeltaPsim), and myocardial ATP and inhibited myocyte oncosis. The increase in myocardial ATP and relocalization of dystrophin to the sarcolemma mediated by IPC was inhibited by treatment with DNP or oligomycin during reperfusion. In vitro experiments demonstrated that mitochondria isolated from the ischemic IPC heart increased ATP generation and facilitated relocalization of dystrophin from the insoluble to the soluble fractions in a manner sensitive to DNP and oligomycin.
  
  
  CONCLUSIONS
  These results suggest that enhanced relocalization of dystrophin to the sarcolemma during reperfusion may be a mechanistic link between IPC-mediated improvement of mitochondrial function and its protection against oncosis during the early phase of reperfusion.
authors.affiliation: Cardiovascular Center, Kansai Medical University, Moriguchi City, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Kyoi
authors.forename: Hajime
authors.initials: H
authors.lastname: Otani
authors.forename: Ayako
authors.initials: A
authors.lastname: Hamano
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsuhisa
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Akita
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Fujiwara
authors.forename: Reiji
authors.initials: R
authors.lastname: Hattori
authors.forename: Hiroji
authors.initials: H
authors.lastname: Imamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamihata
authors.forename: Toshiji
authors.initials: T
authors.lastname: Iwasaka
mesh_terms: D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D002463:Cell Membrane Permeability; D003402:Creatine Kinase / Q000378:metabolism; D016189:Dystrophin / Q000032:analysis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008856:Microscopy, Fluorescence; D015425:Myocardial Reperfusion; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D009942:Organometallic Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000737:chemistry / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D016189:Dystrophin; D004791:Enzyme Inhibitors; D009840:Oligomycins; D009942:Organometallic Compounds; D014475:Uncoupling Agents; C110932:tetramethyl rhodamine ethyl ester; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D019297:2,4-Dinitrophenol