title: Role of Bcl-2 family of proteins in mediating apoptotic death of PC12 cells exposed to oxygen and glucose deprivation.
abstract: Apoptotic cell death has been observed in many in vivo and in vitro models of ischemia. However, the molecular pathways involved in ischemia-induced apoptosis remain unclear. We have examined the role of Bcl-2 family of proteins in mediating apoptosis of PC12 cells exposed to the conditions of oxygen and glucose deprivation (OGD) or OGD followed by restoration of oxygen and glucose (OGD-restoration, OGD-R). OGD decreased mitochondrial membrane potential and induced necrosis of PC12 cells, which were both prevented by the overexpression of Bcl-2 proteins. OGD-R caused apoptotic cell death, induced cytochrome C release from mitochondria and caspase-3 activation, decreased mitochondrial membrane potential, and increased levels of pro-apoptotic Bax translocated to the mitochondrial membrane, all of which were reversed by overexpression of Bcl-2. These results demonstrate that the cell death induced by OGD and OGD-R in PC12 cells is potentially mediated through the regulation of mitochondrial membrane potential by the Bcl-2 family of proteins. It also reveals the importance of developing therapeutic strategies for maintaining the mitochondrial membrane potential as a possible way of reducing necrotic and apoptotic cell death that occurs following an ischemic insult.
authors.affiliation: William T. Gossett Neurology Laboratories, Detroit, MI 48202, USA.
authors.forename: David
authors.initials: D
authors.lastname: Koubi
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhang
authors.forename: Wenxue
authors.initials: W
authors.lastname: Tang
authors.forename: Jarret
authors.initials: J
authors.lastname: Kuo
authors.forename: Alba I
authors.initials: AI
authors.lastname: Rodriguez
authors.forename: Tangella Jackson
authors.initials: TJ
authors.lastname: Hunter
authors.forename: Michael D
authors.initials: MD
authors.lastname: Seidman
authors.forename: George B
authors.initials: GB
authors.lastname: Corcoran
authors.forename: Robert A
authors.initials: RA
authors.lastname: Levine
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D045304:Cytochromes c / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D053938:DNA Fragmentation; D004789:Enzyme Activation / Q000502:physiology; D005434:Flow Cytometry; D005947:Glucose / Q000172:deficiency*; D008564:Membrane Potentials / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D009336:Necrosis; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D051028:bcl-2-Associated X Protein
chemical_list: C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D005947:Glucose