title: The cellular autophagy markers Beclin-1 and LC3B-II are increased during reperfusion in fibrillated mouse hearts.
abstract: Autophagy is an intracellular bulk degradation process for elimination of damaged macromolecules and organelles. In the past decades, the scientific community has gained increasingly detailed understanding of the role of autophagy in myocardial homeostasis, although still many controversies remain. In the ischemic myocardium, autophagy appears to be beneficial for survival, whereas upon reperfusion the process may induce cell death. However, the overall effect of autophagy seems to depend on the duration and intensity of stress, as along with the extent of autophagy within myocardial tissue. Reperfusion of an ischemic heart maybe harmful, but it is an essential process for myocardial survival. One of the major adverse consequences of reperfusion is the occurrence of ventricular fibrillation (VF). In the present study, we investigated the possible connection between autophagy and VF. Isolated mouse hearts were subjected to ischemia/reperfusion (I/R) and divided into two groups based on the development of VF at the beginning of reperfusion. Western blot analysis was conducted for autophagy-associated proteins LC3B, ATG-5, ATG-7, ATG-12, Bcl-2 and Beclin-1 proteins. Significantly higher level of Beclin-1 and LC3B-II/LC3B-I ratio (both definitive autophagy biomarkers) was observed in the fibrillated myocardium, versus tissue from the nonfibrillated hearts. Interestingly, although Bcl-2 is a major regulator of Beclin-1, level of this protein was not significantly altered in tissue from fibrillated, versus non-fibrillated hearts. Moreover, Atg7 expression showed a trend, albeit nonsignificant, towards elevation in fibrillated versus non-fibrillated hearts. Results of the present investigation demonstrate a possible link between VF and autophagy. Studies by authors of this report to evaluate potential etiologic relationships between the two processes are ongoing.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy University of Debrecen, 4032 Debrecen, Hungary. lekli.istvan@pharm.unideb.hu.
authors.forename: Gregory
authors.initials: G
authors.lastname: Meyer
authors.forename: Attila
authors.initials: A
authors.lastname: Czompa
authors.forename: Cyril
authors.initials: C
authors.lastname: Reboul
authors.forename: Evelin
authors.initials: E
authors.lastname: Csepanyi
authors.forename: Andras
authors.initials: A
authors.lastname: Czegledi
authors.forename: Istvan
authors.initials: I
authors.lastname: Bak
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Balla
authors.forename: Jozsef
authors.initials: J
authors.lastname: Balla
authors.forename: Arpad
authors.initials: A
authors.lastname: Tosaki
authors.forename: Istvan
authors.initials: I
authors.lastname: Lekli
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D015415:Biomarkers; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins