A functionalised single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt-TSC2-mTOR signalling

Nanoparticles are now emerging as a novel class of autophagy activators. Functionalised single-walled carbon nanotubes (f-SWCNTs) are valuable nanomaterials in many industries. This article is designed to assess the autophagic response for f-SWCNTs exposure in vitro and in vivo. A few types of f-SWCNTs were screened in human lung adenocarcinoma A549 cells for the autophagic response and related pathways in vitro. Formation of autophagosomes and LC3-II upregulation were confirmed on the basis of electron microscopy and LC3 western blotting for COOH-CNT, but not for PABS-CNT and PEGCNT. MTT assay showed marked increase in cell viability, when COOH-CNT was added to cells in the presence of autophagy inhibitor 3MA, ATG6 or TSC2 siRNA. Consistent with the involvement of the Akt-TSC1/2-mTOR pathway, the phosphorylation levels of mTOR, mTOR’s substrate S6 and Akt were shown significantly decreased in A549 cells on treatment with COOH-CNT using western blotting. What’s more, autophagy inhibitor 3MA significantly reduced the lung oedema in vivo. In a word, COOH-CNT induced autophagic cell death in A549 cells through the AKT-TSC2-mTOR pathway and caused acute lung injury in vivo. Inhibition of autophagy significantly reduced COOH-CNT-induced autophagic cell death and ameliorated acute lung injury in mice, suggesting a potential remedy to address the growing concerns on the safety of nanomaterials.

Authors: Liu, H.-L.; Zhang, Y.-L.; Yang, N.; Zhang, Y.-X.; Liu, X.-Q.; Li, C.-G.; Zhao, Y.; Wang, Y.-G.; Zhang, G.-G.; Yang, P.; Guo, F.; Sun, Y.; Jiang, C.-Y. ;Full Source: Cell Death & Disease [online computer file] 2011, 2(May), e159, 7 pp. (China) ;