Zinc chelation mediates the lysosomal disruption without intracellular ROS generation

• Grant number: 16/03773-9
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Start date: May 01, 2016
• End date: October 31, 2016
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Giselle Cerchiaro
• Grantee: Giselle Cerchiaro
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

In this work we report the molecular mechanism for zinc depletion caused by TPEN (N,N,N',N'-Tetrakis(2-pyridyl-methyl)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 result, we suggest that TPEN causes intracellular zinc depletion that can influence the breakdown of lysosomes and cell death without ROS generation. (AU)