Involvement of intracellular labile zinc in suppression of DEVD-caspase activity in human neuroblastoma cells.
Age-related tissue Zn deficiency may contribute to neuronal and glial cell death by apoptosis in Alzheimer's dementia. To investigate this, we studied the effects of increasing or decreasing the levels of intracellular labile Zn on apoptosis of human neuroblastoma BE(2)-C cells in vitro. BE(2)-C cells were primed for 18 h with butyrate (1 mM) before addition of staurosporine (1 microM), an effector enzyme of apoptosis, for a further 3 h to induce DEVD-caspase activity. An increase in intracellular Zn using Zn ionophore pyrithione suppressed DEVD-caspase activity, while a decrease in intracellular Zn induced by Zn chelator TPEN mimicked staurosporine by activating DEVD-caspase in butyrate-primed cells. The distribution of intracellular Zn in the cells was demonstrated with the UV-excitable Zn-specific fluorophore Zinquin. Confocal images showed distinct cytoplasmic and cytoskeletal fluorescence. We propose that Zn decreases the level of apoptosis in neuronal cells exposed to toxins, possibly by stabilizing their cytoskeleton.
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Department of Medicine, University of Adelaide, Queen Elizabeth Hospital, Woodville, South Australia, 5011, Australia.
Ratnaike
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Zalewski
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D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D003374:Coumarins / Q000378:metabolism*; D004789:Enzyme Activation; D005029:Ethylenediamines / Q000494:pharmacology; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000172:deficiency / Q000378:metabolism*
D061945:Caspase Inhibitors; D002614:Chelating Agents; D003374:Coumarins; D005029:Ethylenediamines; D009842:Oligopeptides; C106566:benzyloxycarbonyl-aspartyl-glutamyl-valyl-aspartyl-7-amino-4-trifluoromethylcoumarin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine