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.
Highlights
Autophagy is a degradation process in eukaryotic cells by which damaged organelles or long-lived proteins are engulfed in double-membrane vesicles for degradation and recycling.[15]
We first analyzed the effects of f-single-walled carbon nanotubes (SWCNTs) by incubating A549 cells with the three different f-SWCNTs: COOH-CNT, PABS-CNT and PEG-CNT, and monitoring cell viability
Our results suggested that autophagic cell death contributed to COOH-CNTs-induced acute lung injury
Summary
Autophagy is a degradation process in eukaryotic cells by which damaged organelles or long-lived proteins are engulfed in double-membrane vesicles for degradation and recycling.[15]. We want to further elucidate whether autophagic cell death, adding to the previous inflammation theory, could have a role in f-SWCNTs-induced acute lung injury. To answer this question, we screened three f-SWCNTs obtained commercially: carboxylic acid (COOH-CNT), polyaminobenzene sulfonic acid (PABS-CNT) and polyethylene glycol (PEG-CNT) in human lung adenocarcinoma A549 cell line for the autophagic response and related pathways in vitro. Received 24.11.10; revised 01.2.11; accepted 14.3.11; Edited by V De Laurenzi f-SWCNT-induced autophagic cell death in lung cell H Liu et al factor in the f-SWCNTs-induced pulmonary toxicity in vivo, hoping to reveal the underlying mechanism of ALI induced by f-SWCNTs, with the goal of providing a potential clinical available remedy for nanoparticles-induced lung injury
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