Cu2+ but not Cd2+ ions at low concentrations increase mitochondrial inner membrane ion permeability by inducing reactive oxygen species production and lipid peroxidation

  • Jolita ČIAPAITĖ
  • Zita NAUČIENĖ
  • Rasa BANIENĖ
  • Odeta BUZAITĖ
  • Vida MILDAŽIENĖ

Anotacija

The integrity of the mitochondrial inner membrane is essential for efficient ATP production in mitochondria. In this study, we analyze the effect of heavy metal ions Cd2+ and Cu2+ at low concentrations on the mitochondrial inner membrane permeability and test the hypothesis that the mechanism of action of Cd2+ and Cu2+ ions is different due to the ability of the latter to undergo redox-cycling and consequently to stimulate the production of reactive oxygen specines (ROS) and to induce lipid peroxidation. We show that 5 nmol Cu2+ per mg of protein but not 5 nmol Cd2+ per mg of protein increase membrane ion permeability in the whole range of the physiologically relevant membrane potential (Δψ) values, especially at high Δψ. Moreover, Cu2+ ions at this concentration enhance the formation of H2O2 in the mitochondrial matrix by 43% and induce lipid peroxidation as indicated by an increase in the amount of thiobarbituric acid reactive substances (TBARS) by 26%. Meanwhile, Cd2+ ions at the same concentration have no significant effect on H2O2 formation or lipid peroxidation. Only a higher amount of Cd2+ions significantly stimulates the formation of H2O2. However, this is not accompanied by an increase in lipid peroxidation, which suggests that, in contrast to Cu2+-induced ROS production, the mechanism of Cd2+-induced ROS production most likely does not involve formation of the hydroxyl radical. In conclusion, we show that Cu2+ but not Cd2+ ions at a low concentration stimulate ROS production and induce accumulation of TBARS, suggesting that, indeed, Cu2+ions increase membrane ion permeability by stimulating lipid peroxidation. Keywords: Cu2+ ions, Cd2+ ions, mitochondria, inner membrane ion permeability, reactive oxygen species, lipid peroxidation
Publikuotas
2007-10-01
Skyrius
Biochemistry