Zinc Oxide Particles Induce Activation of the Lysosome–Autophagy System

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dc.citation.firstpage573en_US
dc.citation.issueNumber1en_US
dc.citation.journalTitleACS Omegaen_US
dc.citation.lastpage581en_US
dc.citation.volumeNumber4en_US
dc.contributor.authorPopp, Laurenen_US
dc.contributor.authorSegatori, Lauraen_US
dc.contributor.orgBioengineeringen_US
dc.contributor.orgChemical and Biomolecular Engineeringen_US
dc.date.accessioned2019-12-05T18:52:39Zen_US
dc.date.available2019-12-05T18:52:39Zen_US
dc.date.issued2019en_US
dc.description.abstractMetal-oxide-based materials are highly versatile and used in a wide variety of applications ranging from medical technology to personal care products. Generally recognized as safe by the US Food and Drug Administration, zinc oxide (ZnO) has been increasingly used in pharmaceutical, cosmetic, food, and commodity chemical industries. As a result, exposure to nano- and micron-sized ZnO particles through occupational processes and consumer products is increasing and has raised concerns over the health effects associated with the large-scale production and commercialization of ZnO-based materials. It is therefore important to investigate the interaction of ZnO particles with biological systems and elucidate the consequent effect on cell physiology. Of particular interest is the autophagic response to zinc oxide particles, as autophagy is the first line of defense activated in response to the uptake of foreign materials. As the main cellular catabolic pathway, the lysosome–autophagy system plays an important homeostatic function and defects or deficiency of this degradation system is associated with the cellular pathogenesis of a number of human diseases, ranging from neurodegenerative disorders to cancer. In this study, we investigated the response of the lysosome–autophagy system to three relevant types of ZnO particles, namely, a polydisperse mixture of bare, micron-sized particles (100–1000 nm) and monodisperse, bare, and coated (with triethoxycaprylylsilane) ZnO nanoparticles (85 nm). To investigate the molecular mechanisms mediating the response of the lysosome–autophagy system to these ZnO particles, we examined a complete set of markers of this pathway and characterized each step, from transcriptional activation to clearance of autophagic cargo. To evaluate the effect of the different types of ZnO particles on the lysosome–autophagy system, biological assays were conducted under conditions that do not cause considerable cytotoxicity. All three types of ZnO particles were found to result in activation of the transcription factor EB, a master regulator of autophagy and lysosomal biogenesis. Cellular exposure to bare and coated nano-sized ZnO enhanced the formation and turnover of autophagosomes and cellular clearance. Cellular exposure to the polydisperse mixture of ZnO particles, however, resulted in enhancement of autophagosome formation, but also in blockage of the autophagic flux. Results from this study underscore the importance of characterizing the autophagic response to ZnO-based materials and contribute significant engineering principles for the future design of nano- and micron-sized ZnO materials with the desired autophagy-modulating properties.en_US
dc.identifier.citationPopp, Lauren and Segatori, Laura. "Zinc Oxide Particles Induce Activation of the Lysosome–Autophagy System." <i>ACS Omega,</i> 4, no. 1 (2019) American Chemical Society: 573-581. https://doi.org/10.1021/acsomega.8b01497.en_US
dc.identifier.digitalacsomega.8b01497en_US
dc.identifier.doihttps://doi.org/10.1021/acsomega.8b01497en_US
dc.identifier.urihttps://hdl.handle.net/1911/107779en_US
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.rightsThis is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.en_US
dc.rights.urihttps://pubs.acs.org/page/policy/authorchoice_termsofuse.htmlen_US
dc.titleZinc Oxide Particles Induce Activation of the Lysosome–Autophagy Systemen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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