Opening of plasma membrane voltage-dependent anion channels (VDAC) precedes caspase activation in neuronal apoptosis induced by toxic stimuli.
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.
Elinder
F
F
Department of Biomedicine and Surgery, Division of Cell Biology, Linköpings Universitet, Linköping SE-581 85, Sweden. fredrik.elinder@ibk.liu.se
Akanda
N
N
Tofighi
R
R
Shimizu
S
S
Tsujimoto
Y
Y
Orrenius
S
S
Ceccatelli
S
S
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
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