Opening of plasma membrane voltage-dependent anion channels (VDAC) precedes caspase activation in neuronal apoptosis induced by toxic stimuli

Cell Death Differ. 2005 Aug;12(8):1134-40. doi: 10.1038/sj.cdd.4401646.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Caspases / metabolism*
  • Cell Line
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Chloride Channels / physiology
  • Electrophysiology
  • Enzyme Activation
  • Hippocampus / cytology
  • Hippocampus / physiology
  • Humans
  • Immunoblotting
  • Immunochemistry
  • Mice
  • NADH, NADPH Oxidoreductases / metabolism
  • Neuroblastoma
  • Neurons / cytology
  • Neurons / enzymology
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Porins / antagonists & inhibitors
  • Porins / metabolism
  • Porins / physiology*
  • Potassium Channels / physiology
  • Voltage-Dependent Anion Channel 1
  • Voltage-Dependent Anion Channels

Substances

  • Chloride Channels
  • Porins
  • Potassium Channels
  • VDAC1 protein, human
  • Vdac1 protein, mouse
  • Voltage-Dependent Anion Channels
  • Adenosine Triphosphate
  • NADH, NADPH Oxidoreductases
  • Voltage-Dependent Anion Channel 1
  • ferricyanide reductase
  • Caspases