Abstract
We report the molecular mechanism for zinc depletion caused by TPEN (N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine) in neuroblastoma cells. The activation of p38 MAP kinase and subsequently caspase 3 is not due to or followed by redox imbalance or ROS generation, though these are commonly observed in literature. We found that TPEN is not responsible for ROS generation and the mechanism involves essentially lysosomal disruption caused by intracellular zinc depletion. We also observed a modest activation of Bax and no changes in the Bcl-2 proteins. As a result, we suggest that TPEN causes intracellular zinc depletion which can influence the breakdown of lysosomes and cell death without ROS generation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Blotting, Western
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Caspase 3 / metabolism
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Cell Line, Tumor
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Cell Survival / drug effects
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Chelating Agents / pharmacology*
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Ethylenediamines / pharmacology
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Flow Cytometry
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Humans
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Intracellular Space / metabolism*
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Lysosomes / drug effects
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Lysosomes / metabolism*
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Necrosis
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Neuroblastoma / pathology
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Reactive Oxygen Species / metabolism*
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Zinc / pharmacology*
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bcl-2-Associated X Protein / metabolism
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Chelating Agents
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Ethylenediamines
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Reactive Oxygen Species
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bcl-2-Associated X Protein
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p38 Mitogen-Activated Protein Kinases
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Caspase 3
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Zinc
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N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine