title: Possible contribution of proteins of Bcl-2 family in neuronal death following transient global brain ischemia.
abstract: Proteins of Bcl-2 family are crucial regulators of intrinsic (mitochondrial) pathway of apoptosis that is implicated among the mechanisms of ischemic neuronal death. Initiation of mitochondrial apoptosis depends on changes of equilibrium between anti-apoptotic and pro-apoptotic proteins of Bcl-2 family as well as on translocation of pro-apoptotic proteins of Bcl-2 family to mitochondria. The aim of this work was to study the effect of transient global brain ischemia on expression and intracellular distribution of proteins of Bcl-2 family in relation to the ischemia-induced changes of ERK and Akt kinase pathways as well as disturbances in ubiquitin proteasome system. Using four vessel occlusion model of transient global brain ischemia, we have shown that both ischemia in duration of 15 min and the same ischemia followed by 1, 3, 24, and 72 h of reperfusion did not affect the levels of either pro-apoptotic (Bad, PUMA, Bim, Bax, Noxa) or anti-apoptotic (Bcl-2, Bcl-xl, Mcl-1) proteins of Bcl-2 family in total cell extracts from rat hippocampus. However, significantly elevated level of Bad protein in the mitochondria isolated from rat hippocampus was observed already 1 h after ischemia and remained elevated 3 and 24 h after ischemia. We did not observe significant changes of the levels of Puma, Bax, Bcl-2, and Bcl-xl in the mitochondria after ischemia and ischemia followed by reperfusion. Our results might indicate possible involvement of Bad translocation to mitochondria in the mechanisms of neuronal death following transient global brain ischemia.
authors.affiliation: Department of Medical Biochemistry, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Martin, Slovak Republic.
authors.forename: Ivana
authors.initials: I
authors.lastname: Pilchova
authors.forename: Katarina
authors.initials: K
authors.lastname: Klacanova
authors.forename: Maria
authors.initials: M
authors.lastname: Chomova
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Tatarkova
authors.forename: Dusan
authors.initials: D
authors.lastname: Dobrota
authors.forename: Peter
authors.initials: P
authors.lastname: Racay
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D016923:Cell Death / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2