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Article

Evidence for Nanoparticle-Induced Lysosomal Dysfunction in Lung Adenocarcinoma (A549) Cells

1
Will Rogers Institute Pulmonary Research Center and Hastings Center for Pulmonary Research, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033-0906, USA
2
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033-0906, USA
3
Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9037, USA
4
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90089-9121, USA
5
Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089-1111, USA
6
Sonny Astani Department of Civil and Environmental Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089-2531, USA
7
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033-9092, USA
8
Mork Family Department of Chemical Engineering and Materials Science, Viterbi School of Engineering, University of Southern California, Los Angeles, CA 90089-1211, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(21), 5253; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20215253
Received: 29 September 2019 / Revised: 20 October 2019 / Accepted: 21 October 2019 / Published: 23 October 2019
(This article belongs to the Special Issue The Alveolar Epithelium: Mechanisms of Injury and Repair)
Background: Polystyrene nanoparticles (PNP) are taken up by primary rat alveolar epithelial cell monolayers (RAECM) in a time-, dose-, and size-dependent manner without involving endocytosis. Internalized PNP in RAECM activate autophagy, are delivered to lysosomes, and undergo [Ca2+]-dependent exocytosis. In this study, we explored nanoparticle (NP) interactions with A549 cells. Methods: After exposure to PNP or ambient pollution particles (PM0.2), live single A549 cells were studied using confocal laser scanning microscopy. PNP uptake and egress were investigated and activation of autophagy was confirmed by immunolabeling with LC3-II and LC3-GFP transduction/colocalization with PNP. Mitochondrial membrane potential, mitophagy, and lysosomal membrane permeability (LMP) were assessed in the presence/absence of apical nanoparticle (NP) exposure. Results: PNP uptake into A549 cells decreased in the presence of cytochalasin D, an inhibitor of macropinocytosis. PNP egress was not affected by increased cytosolic [Ca2+]. Autophagy activation was indicated by increased LC3 expression and LC3-GFP colocalization with PNP. Increased LMP was observed following PNP or PM0.2 exposure. Mitochondrial membrane potential was unchanged and mitophagy was not detected after NP exposure. Conclusions: Interactions between NP and A549 cells involve complex cellular processes leading to lysosomal dysfunction, which may provide opportunities for improved nanoparticle-based therapeutic approaches to lung cancer management. View Full-Text
Keywords: autophagy; lysosome; lysosomal membrane permeability; mitochondria; pneumocyte autophagy; lysosome; lysosomal membrane permeability; mitochondria; pneumocyte
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MDPI and ACS Style

Sipos, A.; Kim, K.-J.; Sioutas, C.; Crandall, E.D. Evidence for Nanoparticle-Induced Lysosomal Dysfunction in Lung Adenocarcinoma (A549) Cells. Int. J. Mol. Sci. 2019, 20, 5253. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20215253

AMA Style

Sipos A, Kim K-J, Sioutas C, Crandall ED. Evidence for Nanoparticle-Induced Lysosomal Dysfunction in Lung Adenocarcinoma (A549) Cells. International Journal of Molecular Sciences. 2019; 20(21):5253. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20215253

Chicago/Turabian Style

Sipos, Arnold, Kwang-Jin Kim, Constantinos Sioutas, and Edward D. Crandall 2019. "Evidence for Nanoparticle-Induced Lysosomal Dysfunction in Lung Adenocarcinoma (A549) Cells" International Journal of Molecular Sciences 20, no. 21: 5253. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20215253

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