Apoptosis

, Volume 6, Issue 6, pp 419–429

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

  • V. M. Kolenko
  • R. G. Uzzo
  • N. Dulin
  • E. Hauzman
  • R. Bukowski
  • J. H. Finke
Article

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.

apoptosis caspases cytochrome c T lymphocytes zinc 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • V. M. Kolenko
    • 1
    • 2
  • R. G. Uzzo
    • 1
    • 3
  • N. Dulin
    • 4
  • E. Hauzman
    • 5
  • R. Bukowski
    • 1
    • 2
  • J. H. Finke
    • 1
    • 3
    • 2
  1. 1.Department of ImmunologyThe Cleveland Clinic FoundationClevelandUSA
  2. 2.Experimental Therapeutics ProgramThe Cleveland Clinic FoundationClevelandUSA
  3. 3.Department of UrologyThe Cleveland Clinic FoundationClevelandUSA
  4. 4.Department of PharmacologyUniversity of Illinois at ChicagoChicagoUSA
  5. 5.Boston Biomedical Research InstituteWatertownUSA

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