Carbon black nanoparticles induce cell necrosis through lysosomal membrane permeabilization and cause subsequent inflammatory response

Yuan, Xia; Nie, Wen; He, Zhiyao; Yang, Jingyun; Shao, Bin; Ma, Xuelei; Zhang, Xiangxian; Bi, Zhenfei; Sun, Lu; Liang, Xiao; Tie, Yan; Liu, Yu; Mo, Fei; Xie, Dan; Wei, Yuquan; Wei, Xiawei

doi:10.7150/thno.34065

Cited by 52 publications

(26 citation statements)

References 66 publications

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“…However, there is some controversy over the FACS histograms. In the majority of studies, the upper left quadrant of the histograms represents necrotic cells (45)(46)(47), while in other instances the upper right quadrant refers to late apoptotic and necrotic cells (48,49). Overall, the right panels, including the lower right quadrant and upper right quadrant are recognized as the apoptotic cells.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol modulates the apoptosis and autophagic death of human lung adenocarcinoma A549 cells via a p53‑dependent pathway: Integrated bioinformatics analysis and experimental validation

Fan

Yang

et al. 2020

Int J Oncol

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Resveratrol (RSV) has been reported to exhibit cytotoxic activity in multiple types of malignant cells; however, the mechanisms underlying the antitumor effects of RSV in non-small-cell lung cancer (NSCLC) cells remain undetermined. Combining bioinformatics analysis with experimental validation, the present study aimed to examine the effects of RSV on the apoptosis and autophagy of A549 NSCLC cells, and to determine the potential underlying molecular mechanisms. Bioinformatics analysis was used to determine the differentially expressed genes (DEGs) and identify the enriched biological functions and pathways associated with these DEGs following RSV treatment. Cell viability was determined by MTT assay, and flow cytometry and TUNEL assay were used to evaluate cell apoptosis. Monodansylcadaverine staining combined with a transmission electron microscope were used to evaluate the extent of autophagy. The expression levels of apoptosis-, autophagy-, or pathway-associated molecular markers were measured by reverse transcription-quantitative PCR and/or western blot analysis. By bioinformatics analysis, a total of 1,031 DEGs were identified in the RSV-treated A549 cells, which were enriched in apoptosis-, or autophagy-related biological functions and the p53 signaling pathway. In validation experiments, RSV significantly reduced cell viability and initiated apoptosis, with an increase in the number of apoptotic cells; it also upregulated cleaved caspase-3 expression and Bax expression, and downregulated the Bcl-2 expression levels. Additionally, there was an increase in the accumulation of green dot-like structures, indicative of autophagic vesicles, observed under a fluorescence microscope, and an increase in the presence of autophagic vacuoles observed using a transmission electron microscope following RSV treatment. Furthermore, the expression levels of the autophagy-related proteins, LC3-II/LC3-I and Beclin-1, were increased and p62 expression was decreased. 3-methyladenine (3-MA), an inhibitor of autophagy, partially reversed the RSV-induced cytotoxic effects, but did not significantly alter the number of apoptotic cells. RSV elevated the p53 levels and decreased the phosphorylated (p-)Mdm2 and p-Akt levels. Pifithrin-α, an inhibitor of p53, partially reduced RSV-induced apoptosis and autophagy. On the whole, the results of the present study demonstrated that RSV initiates the apoptosis and autophagic death of A549 cells via the activation of the p53 signaling pathway, further highlighting the potential of RSV for the treatment of NSCLC.

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Section: Discussionmentioning

confidence: 99%

Resveratrol modulates the apoptosis and autophagic death of human lung adenocarcinoma A549 cells via a p53‑dependent pathway: Integrated bioinformatics analysis and experimental validation

Fan

Yang

et al. 2020

Int J Oncol

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“…Partial LMP, which occurs in only a subpopulation of lysosomes, increases apoptosis [ 46 , 47 ]. In contrast, massive LMP released high concentrations of cathepsins into the cytosol, and then induced necrosis [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells

Min

Kwon

2020

Cancers

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FTY720, a sphingosine-1-phosphate (S1P) receptor modulator, is a synthetic compound produced by the modification of a metabolite from I. sinclairii. Here, we found that FTY720 induced non-apoptotic cell death in human glioma cells (U251MG, U87MG, and U118MG). FTY720 (10 µM) dramatically induced cytoplasmic vacuolation in glioma cells. However, FTY720-mediated vacuolation and cell death are not associated with autophagy. Genetic or pharmacological inhibition of autophagy did not inhibit FTY720-induced cell death. Herein, we detected that FTY720-induced cytoplasmic vacuoles were stained with lysotracker red, and FTY720 induced lysosomal membrane permeabilization (LMP). Interestingly, cathepsin inhibitors (E64D and pepstatin A) and ectopic expression of heat shock protein 70 (HSP70), which is an endogenous inhibitor of LMP, markedly inhibited FTY720-induced cell death. Our results demonstrated that FTY720 induced non-apoptotic cell death via the induction of LMP in human glioma cells.

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“…Thus, all together, the herein described bPEI600-based CDs evoked a dose-dependent lung inflammation. This toxicological effect occurs in the same dose range as that evoked by other carbonaceous nanomaterials, namely carbon black [ 42 , 43 ] and carbon nanotubes [ 18 ]. Furthermore, it is in keeping with the data reported by other groups on ethylenediamine-based CDs [ 31 ], confirming that polyamine surface-passivated cationic CDs trigger adverse outcome in the lung.…”

Section: Resultsmentioning

confidence: 96%

“…Thus, we found that alveolar macrophages are the main cell target of bPEI600-based CDs in the lung. Uptake of NPs by macrophages has been reported for various kinds of nanomaterials [ 42 , 44 ] and is now widely accepted. As alveolar macrophages constitute the first line of defense against foreign materials in the lung [ 45 ], NP engulfing by macrophages plays certainly a central role in alveolar clearance of inhaled NPs, including carbon NPs [ 46 , 47 ].…”

Section: Resultsmentioning

confidence: 99%

Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots

et al. 2021

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With the growth of nanotechnologies, concerns raised regarding the potential adverse effects of nanoparticles (NPs), especially on the respiratory tract. Adverse outcome pathways (AOP) have become recently the subject of intensive studies in order to get a better understanding of the mechanisms of NP toxicity, and hence hopefully predict the health risks associated with NP exposure. Herein, we propose a putative AOP for the lung toxicity of NPs using emerging nanomaterials called carbon dots (CDs), and in vivo and in vitro experimental approaches. We first investigated the effect of a single administration of CDs on mouse airways. We showed that CDs induce an acute lung inflammation and identified airway macrophages as target cells of CDs. Then, we studied the cellular responses induced by CDs in an in vitro model of macrophages. We observed that CDs are internalized by these cells (molecular initial event) and induce a series of key events, including loss of lysosomal integrity and mitochondrial disruption (organelle responses), as well as oxidative stress, inflammasome activation, inflammatory cytokine upregulation and macrophage death (cellular responses). All these effects triggering lung inflammation as tissular response may lead to acute lung injury.

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Carbon black nanoparticles induce cell necrosis through lysosomal membrane permeabilization and cause subsequent inflammatory response

Cited by 52 publications

References 66 publications

Resveratrol modulates the apoptosis and autophagic death of human lung adenocarcinoma A549 cells via a p53‑dependent pathway: Integrated bioinformatics analysis and experimental validation

Resveratrol modulates the apoptosis and autophagic death of human lung adenocarcinoma A549 cells via a p53‑dependent pathway: Integrated bioinformatics analysis and experimental validation

Induction of Lysosomal Membrane Permeabilization Is a Major Event of FTY720-Mediated Non-Apoptotic Cell Death in Human Glioma Cells

Combined In Vitro and In Vivo Approaches to Propose a Putative Adverse Outcome Pathway for Acute Lung Inflammation Induced by Nanoparticles: A Study on Carbon Dots

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