Sodium arsenite exposure alters cell migration, focal adhesion localization and decreases tyrosine phosphorylation of focal adhesion kinase in H9C2 myoblasts

Shannon L Yancy; Eric A Shelden; Robert R Gilmont; Michael J Welsh

doi:10.1093/toxsci/kfi032

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Sodium arsenite exposure alters cell migration, focal adhesion localization and decreases tyrosine phosphorylation of focal adhesion kinase in H9C2 myoblasts

Journal article

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Sodium arsenite exposure alters cell migration, focal adhesion localization and decreases tyrosine phosphorylation of focal adhesion kinase in H9C2 myoblasts

Shannon L Yancy, Eric A Shelden, Robert R Gilmont and Michael J Welsh

Toxicological sciences, Vol.84(2), pp.278-286

04/2005

DOI: https://doi.org/10.1093/toxsci/kfi032

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https://hdl.handle.net/2376/106028

PMID: 15537746

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Abstract

Biomarkers - metabolism

Cell Survival - drug effects

Phosphorylation

Protein-Tyrosine Kinases - metabolism

Focal Adhesion Protein-Tyrosine Kinases

Rats

Cell Adhesion - drug effects

Myoblasts - pathology

Focal Adhesion Kinase 1

Dose-Response Relationship, Drug

Cell Movement - drug effects

Myoblasts - drug effects

Tyrosine - metabolism

Animals

Sodium Compounds - toxicity

Arsenites - toxicity

Enzyme Inhibitors - toxicity

Cell Line, Transformed

Myoblasts - enzymology

Exposure to the environmental toxicant arsenic is reported to produce a variety of effects including disruption of signal transduction pathways, cell proliferation, and apoptosis. This suggests that arsenite may not have specific targets but rather extremely broad effects. The present study was designed to test the hypothesis that arsenite alters signaling involved in focal adhesion structure and function in cultured myoblasts. H9C2 cells were exposed to 1, 2.5, 5, or 10 microM sodium arsenite for 48 h. MTT metabolism and staining by neutral red, trypan blue, and propidium iodide showed that sodium arsenite treatments of 5 microM or less were not overtly cytotoxic. At these doses, sodium arsenite did not affect the amount of polymerized actin in cells, rate of protein synthesis, or amounts of vinculin, talin, paxillin, and focal adhesion kinase (FAK) in cells. However, sodium arsenite-treated cells contained fewer focal adhesions with an altered distribution pattern. Sodium arsenite exposure caused a dose-dependent reduction in cell migration and cell attachment rates. The average area of substrate covered by a cell was also reduced, although the average volume of cells was not significantly affected. Sodium arsenite exposure resulted in reduced tyrosine phosphorylation of FAK, its substrate paxillin and the FAK auto- phosphorylation site, Tyr397. Our results indicate that sodium arsenite can alter focal adhesion structure and function, thus affecting cell attachment and migration and possibly other aspects of focal adhesion function such as integrin signaling. These diverse consequences may be mediated by a relatively specific inhibition of FAK tyrosine phosphorylation, modifying scaffolding proteins.

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Title: Sodium arsenite exposure alters cell migration, focal adhesion localization and decreases tyrosine phosphorylation of focal adhesion kinase in H9C2 myoblasts
Creators: Shannon L Yancy - Toxicology Department, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109-0616, USA
Eric A Shelden
Robert R Gilmont
Michael J Welsh
Publication Details: Toxicological sciences, Vol.84(2), pp.278-286
Academic Unit: Molecular Biosciences, School of
Publisher: United States
Grant note: P01 ES 11188 / NIEHS NIH HHS
Identifiers: 99900546754901842
Language: English
Resource Type: Journal article