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Apoptosis induced by crocidolite asbestos in human lung epithelial cells involves inactivation of Akt and MAPK pathways.
- Source :
-
Apoptosis : an international journal on programmed cell death [Apoptosis] 2007 Feb; Vol. 12 (2), pp. 433-47. - Publication Year :
- 2007
-
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.
- Subjects :
- Buthionine Sulfoximine pharmacology
Caspases metabolism
Cell Line
Enzyme Activation drug effects
Extracellular Signal-Regulated MAP Kinases metabolism
Ferric Compounds pharmacology
Humans
JNK Mitogen-Activated Protein Kinases metabolism
Lung drug effects
Lung enzymology
Phosphatidylinositol 3-Kinases metabolism
Phosphorylation drug effects
Phosphothreonine metabolism
Phosphotyrosine metabolism
Poly(ADP-ribose) Polymerases metabolism
Quaternary Ammonium Compounds pharmacology
Signal Transduction drug effects
Time Factors
p38 Mitogen-Activated Protein Kinases metabolism
Apoptosis drug effects
Asbestos, Crocidolite pharmacology
Epithelial Cells drug effects
Epithelial Cells enzymology
Lung cytology
Mitogen-Activated Protein Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1360-8185
- Volume :
- 12
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Apoptosis : an international journal on programmed cell death
- Publication Type :
- Academic Journal
- Accession number :
- 17191120
- Full Text :
- https://doi.org/10.1007/s10495-006-0577-8