Irreversible disruption of the cytoskeleton as induced by non-cytotoxic exposure to titanium dioxide nanoparticles in lung epithelial cells

Alejandro Déciga-Alcaraz, Norma L. Delgado-Buenrostro, Octavio Ispanixtlahuatl-Meráz, Verónica Freyre-Fonseca, José O. Flores-Flores, Adriana Ganem-Rondero, Felipe Vaca-Paniagua, María del Pilar Ramos-Godinez, Rocío Morales-Barcenas, Yesennia Sánchez-Pérez, Claudia M. García-Cuéllar, Yolanda I. Chirino

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Abstract

Exposure to TiO2 NPs induces several cellular alterations after NPs uptake including disruption of cytoskeleton that is crucial for lung physiology but is not considered as a footprint of cell damage. We aimed to investigate cytoskeleton disturbances and the impact on cell migration induced by an acute TiO2 NPs exposure (24 h) and the recovery capability after 6 days of NPs-free treatment, which allowed investigating if cytoskeleton damage was reversible. Exposure to TiO2 NPs (10 μg/cm2) for 24 h induced a decrease 20.2% and 25.1% in tubulin and actin polymerization. Exposure to TiO2 NPs (10 μg/cm2) for 24 h followed by 6 days of NPs-free had a decrease of 26.6% and 21.3% in tubulin and actin polymerization, respectively. The sustained exposure for 7 days to 1 μg/cm2 and 10 μg/cm2 induced a decrease of 22.4% and 30.7% of tubulin polymerization respectively, and 28.7% and 46.2% in actin polymerization. In addition, 24 h followed 6 days of NPs-free exposure of TiO2 NPs (1 μg/cm2 and 10 μg/cm2) decreased cell migration 40.7% and 59.2%, respectively. Cells exposed (10 μg/cm2) for 7 days had a decrease of 65.5% in cell migration. Ki67, protein surfactant B (SFTPB) and matrix metalloprotease 2 (MMP2) were analyzed as genes related to lung epithelial function. The results showed a 20% of Ki67 upregulation in cells exposed for 24 h to 10 μg/cm2 TiO2 NPs while a downregulation of 20% and 25.8% in cells exposed to 1 μg/cm2 and 10 μg/cm2 for 24 h followed by 6 days of NPs-free exposure. Exposure to 1 μg/cm2 and 10 μg/cm2 for 24 h and 7 days upregulates SFTPB expression in 53% and 59% respectively, MMP2 expression remain unchanged. In conclusion, exposure of TiO2 NPs affected cytoskeleton of lung epithelial cells irreversibly but this damage was not cumulative.

Original languageEnglish
Article number109063
JournalChemico-Biological Interactions
Volume323
DOIs
StatePublished - 25 May 2020
Externally publishedYes

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Keywords

  • Actin
  • Cell migration
  • Cytoskeleton
  • Titanium dioxide nanoparticles
  • Tubulin

Cite this

Déciga-Alcaraz, A., Delgado-Buenrostro, N. L., Ispanixtlahuatl-Meráz, O., Freyre-Fonseca, V., Flores-Flores, J. O., Ganem-Rondero, A., Vaca-Paniagua, F., Pilar Ramos-Godinez, M. D., Morales-Barcenas, R., Sánchez-Pérez, Y., García-Cuéllar, C. M., & Chirino, Y. I. (2020). Irreversible disruption of the cytoskeleton as induced by non-cytotoxic exposure to titanium dioxide nanoparticles in lung epithelial cells. Chemico-Biological Interactions, 323, [109063]. https://doi.org/10.1016/j.cbi.2020.109063