Thimerosal stimulates focal adhesion kinase and cytoskeletal changes by redox modulation.
Thimerosal is one of the most widely used preservatives and has been reported to cause chemically mediated side effects. However, the mechanism of the side effects is not clearly understood yet. In the present study, we showed that HeLa S cells treated by thimerosal generated reactive oxygen species (ROS). Thimerosal-generated ROS stimulated the tyrosine phosphorylation of focal adhesion kinase (FAK) and also induced cytoskeletal changes. Pretreatment with intracellular calcium chelator, BAPTA did not block the thimerosal-mediated FAK tyrosine phosphorylation. On the other hand, either FAK inhibitor, tyrphostin or ROS scavenger, N-acetyl-L-cysteine (NAC) suppressed the tyrosine phosphorylation and cytoskeletal changes. These results suggest that thimerosal seems to induce FAK tyrosine phosphorylation and cytoskeletal changes by ROS generation but not by intracellular calcium mobilization. We think the present finding can be an important clue to understanding the mechanism of thimerosal-mediated side effects, such as contact dermatitis, and allergy.
Kim
Euikyung
E
POSTECH Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, San 31, Hyoja-Dong Nam-Gu, Pohang, Kyungbuk 790-784, South Korea.
Kim
Jung Hwan
JH
Kim
Hyeon Soo
HS
Ryu
Sung Ho
SH
Suh
Pann-Ghill
PG
D000111:Acetylcysteine / Q000494:pharmacology; D000199:Actins / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D016166:Free Radical Scavengers / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D010084:Oxidation-Reduction; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D022502:Stress Fibers / Q000187:drug effects; D013849:Thimerosal / Q000494:pharmacology*; D020032:Tyrphostins / Q000494:pharmacology
D000199:Actins; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D020032:Tyrphostins; D013849:Thimerosal; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; D002118:Calcium; D000111:Acetylcysteine