{"title":"The ROS Mediates MCUb in Mitochondria-Regulated Apoptosis of TM4 Cells Induced by Titanium Dioxide Nanoparticles.","authors":"Chenhao Sun, Qianqian Wang, Pengfei Li, Ruoyun Dong, Yuzhu Lei, Yunhua Hu, Yizhong Yan, Guanling Song","doi":"10.1007/s12011-024-04339-6","DOIUrl":null,"url":null,"abstract":"<p><p>Titanium dioxide nanoparticles (TiO<sub>2</sub> NPs) can cause mitochondrial apoptosis of TM4 cells associated with reactive oxygen species (ROS) accumulation and Ca<sup>2+</sup> overload, but the relations among these processes remain unclear. This study aimed to evaluate whether the accumulation of ROS caused by TiO<sub>2</sub> NPs inhibits MCUb expression, leading to mitochondrial calcium overload and subsequent cell apoptosis through the mitochondrial pathway. TM4 cells were exposed to different concentrations of TiO<sub>2</sub> NPs (0, 25, 50, 75, 100 μg/mL) for 24 h. We assessed cell viability, ROS level, MCUb and VDAC1 expression, mitochondrial and cytoplasmic Ca<sup>2+</sup> levels, mitochondrial membrane potential (MMP), apoptosis rate, and key proteins related to mitochondrial apoptosis (Bcl-2, Bax, Caspase 3, Caspase 9, p53 and Cyt c). Additionally, the effect of N-acetylcysteine (NAC) on MCUb expression, calcium homeostasis, and cell apoptosis was evaluated. Compared to control group, TiO<sub>2</sub> NPs significantly increased ROS level, downregulated MCUb expression, elevated Ca<sup>2+</sup> levels in mitochondria and cytoplasm, and enhanced mitochondria-regulated apoptosis, starting from the 50 μg/mL TiO<sub>2</sub> NPs group. However, NAC significantly increased MCUb expression, attenuated Ca<sup>2+</sup> levels in mitochondria and cytoplasm, and reduced mitochondria-related apoptosis. In conclusion, TiO<sub>2</sub> NPs induced ROS accumulation, which inhibited the expression of MCUb. The decreased MCUb level led to Ca<sup>2+</sup> overload in mitochondria, causing TM4 cell apoptosis via the mitochondrial pathway. This research elucidates, for the first time, the role of MCUb and its relation with ROS in apoptosis of TM4 cells induced by TiO<sub>2</sub> NPs, which supplementing the molecular mechanism of cell apoptosis caused by TiO<sub>2</sub> NPs.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological Trace Element Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s12011-024-04339-6","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Titanium dioxide nanoparticles (TiO2 NPs) can cause mitochondrial apoptosis of TM4 cells associated with reactive oxygen species (ROS) accumulation and Ca2+ overload, but the relations among these processes remain unclear. This study aimed to evaluate whether the accumulation of ROS caused by TiO2 NPs inhibits MCUb expression, leading to mitochondrial calcium overload and subsequent cell apoptosis through the mitochondrial pathway. TM4 cells were exposed to different concentrations of TiO2 NPs (0, 25, 50, 75, 100 μg/mL) for 24 h. We assessed cell viability, ROS level, MCUb and VDAC1 expression, mitochondrial and cytoplasmic Ca2+ levels, mitochondrial membrane potential (MMP), apoptosis rate, and key proteins related to mitochondrial apoptosis (Bcl-2, Bax, Caspase 3, Caspase 9, p53 and Cyt c). Additionally, the effect of N-acetylcysteine (NAC) on MCUb expression, calcium homeostasis, and cell apoptosis was evaluated. Compared to control group, TiO2 NPs significantly increased ROS level, downregulated MCUb expression, elevated Ca2+ levels in mitochondria and cytoplasm, and enhanced mitochondria-regulated apoptosis, starting from the 50 μg/mL TiO2 NPs group. However, NAC significantly increased MCUb expression, attenuated Ca2+ levels in mitochondria and cytoplasm, and reduced mitochondria-related apoptosis. In conclusion, TiO2 NPs induced ROS accumulation, which inhibited the expression of MCUb. The decreased MCUb level led to Ca2+ overload in mitochondria, causing TM4 cell apoptosis via the mitochondrial pathway. This research elucidates, for the first time, the role of MCUb and its relation with ROS in apoptosis of TM4 cells induced by TiO2 NPs, which supplementing the molecular mechanism of cell apoptosis caused by TiO2 NPs.
期刊介绍:
Biological Trace Element Research provides a much-needed central forum for the emergent, interdisciplinary field of research on the biological, environmental, and biomedical roles of trace elements. Rather than confine itself to biochemistry, the journal emphasizes the integrative aspects of trace metal research in all appropriate fields, publishing human and animal nutritional studies devoted to the fundamental chemistry and biochemistry at issue as well as to the elucidation of the relevant aspects of preventive medicine, epidemiology, clinical chemistry, agriculture, endocrinology, animal science, pharmacology, microbiology, toxicology, virology, marine biology, sensory physiology, developmental biology, and related fields.