phosphothreonine and ferric-ammonium-citrate

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.

Topics: Apoptosis; Asbestos, Crocidolite; Buthionine Sulfoximine; Caspases; Cell Line; Enzyme Activation; Epithelial Cells; Extracellular Signal-Regulated MAP Kinases; Ferric Compounds; Humans; JNK Mitogen-Activated Protein Kinases; Lung; Mitogen-Activated Protein Kinases; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinases; Phosphorylation; Phosphothreonine; Phosphotyrosine; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-akt; Quaternary Ammonium Compounds; Signal Transduction; Time Factors