title: A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt-TSC2-mTOR signaling.
abstract: Nanoparticles are now emerging as a novel class of autophagy activators. Functionalized 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 PEG-CNT. 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 edema 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: State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Tsinghua University, Beijing 100005, China.
authors: H-L
authors: HL
authors: Liu
authors: Y-L
authors: YL
authors: Zhang
authors: N
authors: N
authors: Yang
authors: Y-X
authors: YX
authors: Zhang
authors: X-Q
authors: XQ
authors: Liu
authors: C-G
authors: CG
authors: Li
authors: Y
authors: Y
authors: Zhao
authors: Y-G
authors: YG
authors: Wang
authors: G-G
authors: GG
authors: Zhang
authors: P
authors: P
authors: Yang
authors: F
authors: F
authors: Guo
authors: Y
authors: Y
authors: Sun
authors: C-Y
authors: CY
authors: Jiang
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