Academic journal article Environmental Health Perspectives

Lead, Paraquat, and Methylmercury Disrupt Neuronal Stem Cells by a Common Mechanism

Academic journal article Environmental Health Perspectives

Lead, Paraquat, and Methylmercury Disrupt Neuronal Stem Cells by a Common Mechanism

Article excerpt

Li Z, Dong T, Proschel C, Noble M. 2007. Chemically diverse toxicants converge on Fyn and c-Cbl to disrupt precursor cell function. PLoS Biol 5(2):e35.

The quest to establish general principles of mechanism for both known and potential toxicants is a central challenge that fuels investigations in toxicological research. Now groundbreaking research from NIEHS grantee Mark Noble and colleagues at the University of Rochester Medical Center demonstrates that low levels of diverse environmental agents--namely lead, paraquat, and methylmercury--converge on a previously unrecognized regulatory pathway to disrupt the normal functioning of progenitor cells within the central nervous system.

Previous research indicates that many toxicants can increase cells' oxidative status, but questions remain as to how this shared ability relates to toxicant function. In the current study, the investigators conducted work in cell cultures of glial progenitors (advanced-stage stem cells important for the growth, development, and normal functioning of the central nervous system). They exposed the cells to sublethal concentrations of lead, paraquat, and methylmercury.

The cells proved exquisitely sensitive to minute levels of the toxicants, and the researchers found a previously unknown mechanism by which these agents cause the effects. They noted that the agents increased cell oxidation, which activated an enzyme known as Fyn kinase. …

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