Zinc Chelation Mediates the Lysosomal Disruption without Intracellular ROS Generation

Author(s)

Matias, Andreza Candido ; Manieri, Tania Maria ; Cerchiaro, Giselle

• Document type: Journal article
• Source: OXIDATIVE MEDICINE AND CELLULAR LONGEVITY; v. 2016, p. 13-pg., 2016-01-01.

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. (AU)

• FAPESP's process: 12/01397-9 - Effects of metalloenzyme superoxide dismutase expression in the generation of reactive oxygen species in cultured mammalian cells and in motor neurons
• Grantee: Giselle Cerchiaro
• Support Opportunities: Regular Research Grants