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A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt–TSC2-mTOR signaling

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-SWC...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122114/
https://www.ncbi.nlm.nih.gov/pubmed/21593791
http://dx.doi.org/10.1038/cddis.2011.27
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author 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
author_facet 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
author_sort Liu, H-L
collection PubMed
description 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.
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spelling pubmed-31221142011-07-05 A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt–TSC2-mTOR signaling 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 Cell Death Dis Original Article 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. Nature Publishing Group 2011-05 2011-05-19 /pmc/articles/PMC3122114/ /pubmed/21593791 http://dx.doi.org/10.1038/cddis.2011.27 Text en Copyright © 2011 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Original Article
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
A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt–TSC2-mTOR signaling
title A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt–TSC2-mTOR signaling
title_full A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt–TSC2-mTOR signaling
title_fullStr A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt–TSC2-mTOR signaling
title_full_unstemmed A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt–TSC2-mTOR signaling
title_short A functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through Akt–TSC2-mTOR signaling
title_sort functionalized single-walled carbon nanotube-induced autophagic cell death in human lung cells through akt–tsc2-mtor signaling
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3122114/
https://www.ncbi.nlm.nih.gov/pubmed/21593791
http://dx.doi.org/10.1038/cddis.2011.27
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