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

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