Apoptosis

, Volume 6, Issue 6, pp 419–429

Mechanism of apoptosis induced by zinc deficiency in peripheral blood T lymphocytes

Authors

  • V. M. Kolenko
    • Department of ImmunologyThe Cleveland Clinic Foundation
    • Experimental Therapeutics ProgramThe Cleveland Clinic Foundation
  • R. G. Uzzo
    • Department of ImmunologyThe Cleveland Clinic Foundation
    • Department of UrologyThe Cleveland Clinic Foundation
  • N. Dulin
    • Department of PharmacologyUniversity of Illinois at Chicago
  • E. Hauzman
    • Boston Biomedical Research Institute
  • R. Bukowski
    • Department of ImmunologyThe Cleveland Clinic Foundation
    • Experimental Therapeutics ProgramThe Cleveland Clinic Foundation
  • J. H. Finke
    • Department of ImmunologyThe Cleveland Clinic Foundation
    • Department of UrologyThe Cleveland Clinic Foundation
    • Experimental Therapeutics ProgramThe Cleveland Clinic Foundation
Article

DOI: 10.1023/A:1012497926537

Cite this article as:
Kolenko, V.M., Uzzo, R.G., Dulin, N. et al. Apoptosis (2001) 6: 419. doi:10.1023/A:1012497926537

Abstract

Alterations in intracellular Zn2+ concentrations are believed to play a crucial role in modulating apoptosis. The observation that Zn2+ deficiency can induce cell death both in vivo and in vitro has been attributed to the fact that exchange of Zn2+ for Ca2+ and Mg2+ within the nuclei may directly activate endogenous endonucleases therefore inducing DNA fragmentation independent of cytoplasmic factors. Here we show that the membrane-permeable zinc chelator, N,N′,N′-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) induces translocation of cytochrome c from the mitochondrial intramembranous space into the cytosol in human peripheral blood T lymphocytes (PBL) with subsequent activation of caspases-3, -8, and -9. Pretreatment of T lymphocytes with caspase inhibitors Z-VAD.fmk or DEVD.fmk prevented DNA fragmentation in response to TPEN indicating that apoptosis triggered by zinc deficiency is entirely dependent on activation of caspase family members. The release of cytochrome c and activation of downstream caspases precedes changes in the mitochondrial transmembrane potential (Δ Ψm). Therefore, cytoplasmic and mitochondrial events are critical to this process.

apoptosiscaspasescytochrome cT lymphocyteszinc

Copyright information

© Kluwer Academic Publishers 2001