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Zinc Chelation Mediates the Lysosomal Disruption without Intracellular ROS Generation.

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.

SUBMITTER: Matias AC

PROVIDER: S-EPMC4829717 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Zinc Chelation Mediates the Lysosomal Disruption without Intracellular ROS Generation.

Matias Andreza Cândido AC Manieri Tânia Maria TM Cerchiaro Giselle G

Oxidative medicine and cellular longevity 20160330

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 modes ...[more]

PMID: 27123155

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