AKT/mTOR and C-Jun N-terminal Kinase (JNK) Signaling Pathways Are Required for Chrysotile Asbestos-Induced Autophagy.

AKT/mTOR and C-Jun N-terminal Kinase (JNK) Signaling Pathways Are Required for Chrysotile Asbestos-Induced Autophagy. Free Radic Biol Med. 2014 Apr 12; Authors: Lin Z, Liu T, Kamp DW, Wang Y, He H, Zhou X, Li D, Yang L, Zhao B, Liu G Abstract Chrysotile asbestos is closely associated with excess mortality from pulmonary diseases such as lung cancer, mesothelioma, and asbestosis. Although multiple mechanisms in which chrysotile asbestos fibers induce pulmonary disease have been identified, the role of autophagy in human lung epithelial cells has not been examined. In the present study, we evaluated whether chrysotile asbestos induces autophagy in A549 human lung epithelial cells, and then analyzed the possible underlying molecular mechanism. Chrysotile asbestos-induced autophagy in A549 cells based on a series of biochemical and microscopic autophagy markers. We observed that asbestos increased A549 cell microtubule-associated protein 2 light chains 3 (LC3-II) expression, an autophagy marker, in conjunction with dephosphorylation of phospho-AKT, phospho-mTOR, and phospho-P70s6k. Notably, AKT1/AKT2 double knockout (AKT DKO) murine embryonic fibroblasts (MEFs) had negligible asbestos-induced LC3-II expression supporting a crucial role for AKT signaling. Chrysotile asbestos also led to the phosphorylation/activation of Jun N-terminal kinase (JNK) and p38 MAPK. Pharmacologic inhibition of JNK, but not p38 MAPK, dramatically inhibited the ...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research