Titanium Dioxide Induces Apoptosis under UVA Irradiation via the Generation of Lysosomal Membrane Permeabilization-Dependent Reactive Oxygen Species in HaCat Cells.

In Young Kim,Min Beom Heo,Vytas Reipa,Tae Geol Lee

doi:10.3390/nano11081943

Abstract

Titanium dioxide nanoparticles (TiO2 NPs) have wide commercial applications, owing to their small size; however, the biosafety of TiO2 NPs should be evaluated further. In this study, we aimed to investigate the cytotoxicity of TiO2 NPs in the presence and absence of ultraviolet A (UVA) irradiation in human keratinocyte HaCaT cells. TiO2 NPs did not significantly affect cell viability in the absence of UVA irradiation. Nonetheless, UVA-irradiated TiO2 NPs induced caspase-dependent apoptosis of HaCaT cells. Exposure of HaCaT cells to TiO2 NPs and UVA resulted in reactive oxygen species (ROS) generation and lysosomal membrane permeabilization (LMP); both effects were not observed in the absence of UVA irradiation. An analysis of the relationship between LMP and ROS, using CA-074 as a cathepsin inhibitor or NAC as an antioxidant, showed that LMP stimulates ROS generation under these conditions. These results imply that LMP-dependent oxidative stress plays a critical role in the UVA phototoxicity of TiO2 NPs in HaCaT cells.

Highlights

The loss of lysosomal membrane integrity is essential for TiO2 NPs and ultraviolet A (UVA)-induced reactive oxygen species (ROS) surge
Since NP size distribution can undergo significant changes when transferred to environments used for biological studies [51], we characterized the dispersions of TiO2 NPs in deionized water (DIW) and media by measuring size distributions and zeta potential values (Figure 2c)
As our results suggested that lysosomal membranes were altered by the combination of TiO2 NPs and UVA, we tested the lysosomal integrity of HaCaT cells by staining them with acridine orange (AO)

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The potential toxicity of nanomaterials (NMs) to humans and the environment has been recognized since the dawn of nanotechnology [1]. This is because their physicochemical properties are highly dependent on small particle size, resulting in a high surface-tovolume ratio and enhanced transport across biological barriers [2]. Some materials, while benign in bulk form, become toxic when prepared in nano sizes [3]

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