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Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 6724585, 13 pages
Research Article

Zinc Chelation Mediates the Lysosomal Disruption without Intracellular ROS Generation

Center for Natural Sciences and Humanities, Federal University of ABC, UFABC, Avenida dos Estados 5001, Bloco B, 09210-170 Santo André, SP, Brazil

Received 12 November 2015; Revised 23 February 2016; Accepted 8 March 2016

Academic Editor: Tetsuro Kamiya

Copyright © 2016 Andreza Cândido Matias et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.