Apoptosis induced by crocidolite asbestos in human lung epithelial cells involves inactivation of Akt and MAPK pathways |
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Authors: | Aleksander Baldys Priyadarshini Pande Tariq Mosleh Sun-Hee Park Ann E Aust |
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Institution: | (1) Department of Chemistry and Biochemistry, Utah State University, Logan, UT 84322-0300, USA |
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Abstract: | Exposure of human lung epithelial (A549) cells to asbestos fibers causes apoptosis, which is largely attributed to release
of iron and generation of reactive oxygen species (ROS) within the cells. To mimic the highly oxidative environment generated
by asbestos exposure in the absence of the actual fibers, we used two chemicals; buthione sulfoximine (BSO), an inhibitor
of glutathione (GSH) synthesis and ferric ammonium citrate (FAC), a source of iron. Here, we report that exposure of A549
cells to crocidolite asbestos led to a significant time-dependent inactivation of signaling proteins, i.e. Akt and all mitogen-activated
protein kinases (MAPKs) (p38, ERK1/2 and SAPK/JNK), and subsequently to apoptosis. Unlike crocidolite treatment, the use of
BSO and FAC, independently or combined, did not change the phosphorylation status of proteins, nor did it induce apoptosis.
Taken together, our results presented herein point to the possibility that crocidolite-induced apoptosis of human lung epithelial
cells is not a mere consequence of generation of oxidants but also requires inactivation of major cell growth and differentiation
pathways.
A. Baldys, P. Pande contributed equally to this publication. |
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Keywords: | Asbestos Apoptosis MAPK Akt Iron Glutathione |
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