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

Liu, HL; Yl, Zhang; Yang, Neng; Yx, Zhang; Xq, Liu; Cg, Li; Zhao, Ying; Wang, Y-G; Gg, Zhang; Yang, Peng; Guo, Feng; Sun, Yukun; Jiang, C-Y

doi:10.1038/cddis.2011.27

Cited by 169 publications

(101 citation statements)

References 35 publications

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“…In addition to our recent studies showing that autophagy mediates cigarette smoking-induced lung epithelial damage (2,4,5,36), other works have also demonstrated that autophagy positively regulates lung injury induced by influenza H5N1 (33,38), nanomaterials (21,23), and ventilation (24). Thus inhibition of autophagy might represent a valuable therapeutic target in certain lung diseases (30), and preservation of Cav-1 might acquire therapeutic benefits in these diseases.…”

Section: Discussionmentioning

confidence: 71%

Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells

Chen

Cao

Zhou

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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AM, Shen H. Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 306: L1016 -L1025, 2014. First published April 11, 2014 doi:10.1152/ajplung.00268.2013.-Autophagy plays a pivotal role in cellular homeostasis and adaptation to adverse environments, although the regulation of this process remains incompletely understood. We have recently observed that caveolin-1 (Cav-1), a major constituent of lipid rafts on plasma membrane, can regulate autophagy in cigarette smoking-induced injury of lung epithelium, although the underlying molecular mechanisms remain incompletely understood. In the present study we found that Cav-1 interacted with and regulated the expression of ATG12-ATG5, an ubiquitin-like conjugation system crucial for autophagosome formation, in lung epithelial Beas-2B cells. Deletion of Cav-1 increased basal and starvation-induced levels of ATG12-ATG5 and autophagy. Biochemical analyses revealed that Cav-1 interacted with ATG5, ATG12, and their active complex ATG12-ATG5. Overexpression of ATG5 or ATG12 increased their interactions with Cav-1, the formation of ATG12-ATG5 conjugate, and the subsequent basal levels of autophagy but resulted in decreased interactions between Cav-1 and another molecule. Knockdown of ATG12 enhanced the ATG5-Cav-1 interaction. Mutation of the Cav-1 binding motif on ATG12 disrupted their interaction and further augmented autophagy. Cav-1 also regulated the expression of ATG16L, another autophagy protein associating with the ATG12-ATG5 conjugate during autophagosome formation. Altogether these studies clearly demonstrate that Cav-1 competitively interacts with the ATG12-ATG5 system to suppress the formation and function of the latter in lung epithelial cells, thereby providing new insights into the molecular mechanisms by which Cav-1 regulates autophagy and suggesting the important function of Cav-1 in certain lung diseases via regulation of autophagy homeostasis.caveolin-1; ATG12-ATG5; ATG16L; autophagy; lung diseases AUTOPHAGY IS A DYNAMIC PROCESS responsible for the turnover of cellular organelles and long-lived proteins. During this process, cytosolic proteins and organelles (e.g., mitochondria and endoplasmic reticulum) are engulfed into double-membranebound vesicles, autophagosomes. The outer membrane of the autophagosome subsequently fuses with lysosomes to form autolysosomes in which the engulfed components are degraded by lysosomal hydrolases, regenerating metabolic precursors that are recycled for macromolecular synthesis and ATP generation (20, 42). Autophagy is induced above basal levels in response to diverse stimuli including nutrient starvation, genotoxic agents, cytokines, and oxidative stress. This process provides an essential function in the maintenance of cellular homeostasis and adaptation to adverse environments (16,29,35).More than 30 autophagy-related genes and gene products critical in the regulation of autophagy, designated "ATG," have been identified heretofore in yeast and hi...

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Section: Discussionmentioning

confidence: 71%

Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells

Chen

Cao

Zhou

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…10 So far, findings have presented a paradox: some reported that the autophagy induced by NPs could promote cell death, but in other conditions it could be a protective role in response to toxicity caused by NPs. 1,11,12 To the best of our knowledge, there is no report on autophagy caused by SPIONs in human monocyte cells.…”

Section: Introductionmentioning

confidence: 99%

Iron oxide nanoparticles and induced autophagy in human monocytes

Jin²,

Feng

et al. 2017

IJN

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Superparamagnetic iron oxide nanoparticles have been widely used in biomedical applications, but understanding of their interactions with the biological immune system is relatively limited. This work is focused on dextran-coated iron oxide nanoparticles and their induced autophagy in human monocytes. We found that these nanoparticles can be taken up by human monocytes, followed by localization within vesicles or free in cytoplasm. Autophagosome formation was observed with increased expression of LC3II protein, the specific marker of autophagy. The autophagy substrate p62 was degraded in a dose-dependent manner, and autophagy was blocked by autophagy (or lysosome) inhibitors alone or along with iron oxide nanoparticles, indicating that autophagosome accumulation was mainly due to autophagy induction, rather than blockade of autophagy flux. Interestingly, iron oxide nanoparticles increased the viability of human monocytes, but the mechanism was not clear. We further found that inhibition of autophagy mostly attenuated the survival of cells, with acceleration of the inflammation induced by these nanoparticles. Taken together, autophagic activation in human monocytes may play a protective role against the cytotoxicity of iron oxide nanoparticles.

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“…1 For example, single wall carbon nanotubes (SWCNTs) modified by the addition of phenyl-(COOH) 2 functional groups has demonstrated a stronger cytotoxic effect than SWCNT-phenyl-SO 3 H. 13 Furthermore, COOH functionalized CNTs significantly induced autophagic cell death in human lung cells when compared to polyaminobenzenesulfonic acid (PABS) and polyethylene glycol (PEG) functionalized SWCNTs. 14 These studies suggest that the transformation of CNTs in the environment, resulting in their functionalization, has the potential to alter their toxicity.…”

Section: ■ Introductionmentioning

confidence: 99%

Chemical and Toxicological Evolution of Carbon Nanotubes During Atmospherically Relevant Aging Processes

Liggio

Breznan

et al. 2015

Environ. Sci. Technol.

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The toxicity of carbon nanotubes (CNTs) has received significant attention due to their usage in a wide range of commercial applications. While numerous studies exist on their impacts in water and soil ecosystems, there is a lack of information on the exposure to CNTs from the atmosphere. The transformation of CNTs in the atmosphere, resulting in their functionalization, may significantly alter their toxicity. In the current study, the chemical modification of single wall carbon nanotubes (SWCNTs) via ozone and OH radical oxidation is investigated through studies that simulate a range of expected tropospheric particulate matter (PM) lifetimes, in order to link their chemical evolution to toxicological changes. The results indicate that the oxidation favors carboxylic acid functionalization, but significantly less than other studies performed under nonatmospheric conditions. Despite evidence of functionalization, neither O 3 nor OH radical oxidation resulted in a change in redox activity (potentially giving rise to oxidative stress) or in cytotoxic end points. Conversely, both the redox activity and cytotoxicity of SWCNTs significantly decreased when exposed to ambient urban air, likely due to the adsorption of organic carbon vapors. These results suggest that the effect of gas−particle partitioning of organics in the atmosphere on the toxicity of SWCNTs should be investigated further.

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

Cited by 169 publications

References 35 publications

Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells

Interaction of caveolin-1 with ATG12-ATG5 system suppresses autophagy in lung epithelial cells

Iron oxide nanoparticles and induced autophagy in human monocytes

Chemical and Toxicological Evolution of Carbon Nanotubes During Atmospherically Relevant Aging Processes

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