title: Opening of plasma membrane voltage-dependent anion channels (VDAC) precedes caspase activation in neuronal apoptosis induced by toxic stimuli.
abstract: Apoptotic cell death is an essential process in the development of the central nervous system and in the pathogenesis of its degenerative diseases. Efflux of K(+) and Cl(-) ions leads to the shrinkage of the apoptotic cell and facilitates the activation of caspases. Here, we present electrophysiological and immunocytochemical evidences for the activation of a voltage-dependent anion channel (VDAC) in the plasma membrane of neurons undergoing apoptosis. Anti-VDAC antibodies blocked the channel and inhibited the apoptotic process. In nonapoptotic cells, plasma membrane VDAC1 protein can function as a NADH (-ferricyanide) reductase. Opening of VDAC channels in apoptotic cells was associated with an increase in this activity, which was partly blocked by VDAC antibodies. Hence, it appears that there might be a dual role for this protein in the plasma membrane: (1) maintenance of redox homeostasis in normal cells and (2) promotion of anion efflux in apoptotic cells.
authors.affiliation: Department of Biomedicine and Surgery, Division of Cell Biology, Linköpings Universitet, Linköping SE-581 85, Sweden. fredrik.elinder@ibk.liu.se
authors.forename: F
authors.initials: F
authors.lastname: Elinder
authors.forename: N
authors.initials: N
authors.lastname: Akanda
authors.forename: R
authors.initials: R
authors.lastname: Tofighi
authors.forename: S
authors.initials: S
authors.lastname: Shimizu
authors.forename: Y
authors.initials: Y
authors.lastname: Tsujimoto
authors.forename: S
authors.initials: S
authors.lastname: Orrenius
authors.forename: S
authors.initials: S
authors.lastname: Ceccatelli
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018118:Chloride Channels / Q000502:physiology; D004594:Electrophysiology; D004789:Enzyme Activation; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D007120:Immunochemistry; D051379:Mice; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D018272:Porins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D050995:Voltage-Dependent Anion Channel 1; D050994:Voltage-Dependent Anion Channels
chemical_list: D018118:Chloride Channels; D018272:Porins; D015221:Potassium Channels; C494762:VDAC1 protein, human; C494763:Vdac1 protein, mouse; D050994:Voltage-Dependent Anion Channels; D000255:Adenosine Triphosphate; D009247:NADH, NADPH Oxidoreductases; D050995:Voltage-Dependent Anion Channel 1; C014227:ferricyanide reductase; D020169:Caspases