Depletion of intracellular zinc induces macromolecule synthesis- and caspase-dependent apoptosis of cultured retinal cells

Hyae Jung Hyun, Joonhong Sohn, Young Ho Ahn, Hyung Cheul Shin, Jae Young Koh, Young Hee Yoon

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51 Scopus citations

Abstract

Although zinc deficiency may contribute to age-related macular degeneration (ARMD), the pathogenic mechanism is as yet uncertain. In light of evidence that cellular zinc depletion induces apoptosis in cortical neurons and thymocytes, in the present study, we examined the possibility that the same phenomenon occurs also in retinal cells. Exposure of primary retinal cell cultures to 1-3 μM of a cell membrane-permeant zinc chelator TPEN for 24 h induced concentration-dependent death of neurons, photoreceptor cells, and astrocytes. Addition of zinc or copper reversed TPEN toxicity to all cell components, indicating the particular involvement of zinc chelation in cell death. Consistent with apoptosis, oligonucleosomal DNA fragmentation and chromatin condensation accompanied, and the protein synthesis inhibitor cycloheximide blocked the TPEN-induced retinal cell death. During TPEN-induced retinal cell apoptosis, cleavage/activation of procaspase-1, but little of procaspase-3, was observed. Consistent with this finding, a broad-spectrum caspase inhibitor (zVAD-fmk) was significantly more protective than a caspase-3-selective inhibitor (DEVD-fmk). The present study has demonstrated that depletion of intracellular zinc is sufficient to induce macromolecule synthesis- and caspase-dependent apoptosis of cultured retinal cells. In light of the possibility that zinc depletion may contribute to the pathogenesis of ARMD, the current culture model may be a useful tool for the investigation of the mechanism of zinc depletion-induced retinal cell death. Theme: Disorders of the nervous system. Topic: Neurotoxicity. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)39-48
Number of pages10
JournalBrain Research
Volume869
Issue number1-2
DOIs
StatePublished - 30 Jun 2000

Keywords

  • Cycloheximide
  • DEVD
  • Excitotoxicity
  • Macular degeneration
  • TPEN
  • zVAD

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