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Internalization of Titanium Dioxide Nanoparticles Is Mediated by Actin-Dependent Reorganization and Clathrin- and Dynamin-Mediated Endocytosis in H9c2 Rat Cardiomyoblasts
División Académica Multidisciplinaria de Comalcalco, Universidad Juárez Autónoma Tabasco, Comalcalco, Tabasco, México.
Departamento de Microscopía Electrónica, Ciudad de México, México .
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología, Ciudad de México, México.
Örebro University, School of Science and Technology. of Environmental Health, Karolinska Institute, Stockholm, Sweden. (Man-Technology-Environment research centre (MTM))ORCID iD: 0000-0003-1132-7992
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2019 (English)In: Chemical Research in Toxicology, ISSN 0893-228X, E-ISSN 1520-5010, Vol. 32, no 4, p. 578-588Article in journal (Refereed) Published
Abstract [en]

Titanium dioxide nanoparticles (TiO2 NPs) are widely used for industrial and commercial applications. Once inside the body, they translocate into the bloodstream and reach different areas of the cardiovascular system including the heart, increasing the risk of developing cardiovascular diseases; consequently, the investigation of their interaction with cardiac cells is required. We previously showed that TiO2 NPs are internalized by H9c2 rat cardiomyoblasts, and here, we examined the molecular mechanisms underlying this process. TiO2 NPs internalization was evaluated by transmission electron microscopy, time-lapse microscopy, and flow cytometry. Changes in the actin cytoskeleton were studied by phalloidin staining. Endocytic uptake mechanisms for nanoparticles were probed with chemical inhibitors, whereas clathrin and dynamin expression was measured by Western blot. Cellular uptake of TiO2 NPs occurred early after 30 min exposure, and large aggregates were observed after 1 h. Actin cytoskeleton reorganization included cell elongation plus lower density and stability of actin fibers. Cytochalasin-D inhibited TiO2 NPs uptake, indicating actin-mediated internalization. Dynamin and clathrin levels increased early after TiO2 NPs exposure, and their inhibition reduced nanoparticle uptake. Therefore, TiO2 NPs internalization by H9c2 rat cardiomyoblasts involves actin cytoskeleton reorganization and clathrin/dynamin-mediated endocytosis.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2019. Vol. 32, no 4, p. 578-588
National Category
Cell Biology Pharmacology and Toxicology
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URN: urn:nbn:se:oru:diva-72884DOI: 10.1021/acs.chemrestox.8b00284ISI: 000465190200007PubMedID: 30730135Scopus ID: 2-s2.0-85062568137OAI: oai:DiVA.org:oru-72884DiVA, id: diva2:1293234
Note

Funding Agency:

CONACyT  295174  570169

Available from: 2019-03-04 Created: 2019-03-04 Last updated: 2019-06-19Bibliographically approved

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Alfaro-Moreno, Ernesto

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