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Ultrafine silicon dioxide nanoparticles cause lung epithelial cells apoptosis via oxidative stress-activated PI3K/Akt-mediated mitochondria- and endoplasmic reticulum stress-dependent signaling pathways.
Sci Rep. 2020 06 18; 10(1):9928.SR

Abstract

Silicon dioxide nanoparticles (SiO2NPs) are widely applied in industry, chemical, and cosmetics. SiO2NPs is known to induce pulmonary toxicity. In this study, we investigated the molecular mechanisms of SiO2NPs on pulmonary toxicity using a lung alveolar epithelial cell (L2) model. SiO2NPs, which primary particle size was 12 nm, caused the accumulation of intracellular Si, the decrease in cell viability, and the decrease in mRNAs expression of surfactant, including surfactant protein (SP)-A, SP-B, SP-C, and SP-D. SiO2NPs induced the L2 cell apoptosis. The increases in annexin V fluorescence, caspase-3 activity, and protein expression of cleaved-poly (ADP-ribose) polymerase (PARP), cleaved-caspase-9, and cleaved-caspase-7 were observed. The SiO2NPs induced caspase-3 activity was reversed by pretreatment of caspase-3 inhibitor Z-DEVD-FMK. SiO2NPs exposure increased reactive oxygen species (ROS) production, decreased mitochondrial transmembrane potential, and decreased protein and mRNA expression of Bcl-2 in L2 cells. SiO2NPs increased protein expression of cytosolic cytochrome c and Bax, and mRNAs expression of Bid, Bak, and Bax. SiO2NPs could induce the endoplasmic reticulum (ER) stress-related signals, including the increase in CHOP, XBP-1, and phospho-eIF2α protein expressions, and the decrease in pro-caspase-12 protein expression. SiO2NPs increased phosphoinositide 3-kinase (PI3K) activity and AKT phosphorylation. Both ROS inhibitor N-acetyl-l-cysteine (NAC) and PI3K inhibitor LY294002 reversed SiO2NPs-induced signals described above. However, the LY294002 could not inhibit SiO2NPs-induced ROS generation. These findings demonstrated first time that SiO2NPs induced L2 cell apoptosis through ROS-regulated PI3K/AKT signaling and its downstream mitochondria- and ER stress-dependent signaling pathways.

Authors+Show Affiliations

Department of Emergency, Taichung Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, No.66 Section 1, Fongsing Rd., Tanzih Township, Taichung, 427, Taiwan.Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua, 500, Taiwan. School of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.Department of Otolaryngology, Far Eastern Memorial Hospital, New Taipei City, 220, Taiwan.Department of Public Health, China Medical University, Taichung, 404, Taiwan.Department of Nutrition and Master Program of Food and Drug Safety, China Medical University, Taichung, 40402, Taiwan.Department of Physiology, College of Medicine, China Medical University, No.91 Hsueh-Shih Road, Taichung, 404, Taiwan. d91447001@ntu.edu.tw.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32555254

Citation

Lee, Kuan-I, et al. "Ultrafine Silicon Dioxide Nanoparticles Cause Lung Epithelial Cells Apoptosis Via Oxidative Stress-activated PI3K/Akt-mediated Mitochondria- and Endoplasmic Reticulum Stress-dependent Signaling Pathways." Scientific Reports, vol. 10, no. 1, 2020, p. 9928.
Lee KI, Su CC, Fang KM, et al. Ultrafine silicon dioxide nanoparticles cause lung epithelial cells apoptosis via oxidative stress-activated PI3K/Akt-mediated mitochondria- and endoplasmic reticulum stress-dependent signaling pathways. Sci Rep. 2020;10(1):9928.
Lee, K. I., Su, C. C., Fang, K. M., Wu, C. C., Wu, C. T., & Chen, Y. W. (2020). Ultrafine silicon dioxide nanoparticles cause lung epithelial cells apoptosis via oxidative stress-activated PI3K/Akt-mediated mitochondria- and endoplasmic reticulum stress-dependent signaling pathways. Scientific Reports, 10(1), 9928. https://doi.org/10.1038/s41598-020-66644-z
Lee KI, et al. Ultrafine Silicon Dioxide Nanoparticles Cause Lung Epithelial Cells Apoptosis Via Oxidative Stress-activated PI3K/Akt-mediated Mitochondria- and Endoplasmic Reticulum Stress-dependent Signaling Pathways. Sci Rep. 2020 06 18;10(1):9928. PubMed PMID: 32555254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ultrafine silicon dioxide nanoparticles cause lung epithelial cells apoptosis via oxidative stress-activated PI3K/Akt-mediated mitochondria- and endoplasmic reticulum stress-dependent signaling pathways. AU - Lee,Kuan-I, AU - Su,Chin-Chuan, AU - Fang,Kai-Min, AU - Wu,Chin-Ching, AU - Wu,Cheng-Tien, AU - Chen,Ya-Wen, Y1 - 2020/06/18/ PY - 2019/10/30/received PY - 2020/04/06/accepted PY - 2020/6/20/entrez PY - 2020/6/20/pubmed PY - 2020/12/15/medline SP - 9928 EP - 9928 JF - Scientific reports JO - Sci Rep VL - 10 IS - 1 N2 - Silicon dioxide nanoparticles (SiO2NPs) are widely applied in industry, chemical, and cosmetics. SiO2NPs is known to induce pulmonary toxicity. In this study, we investigated the molecular mechanisms of SiO2NPs on pulmonary toxicity using a lung alveolar epithelial cell (L2) model. SiO2NPs, which primary particle size was 12 nm, caused the accumulation of intracellular Si, the decrease in cell viability, and the decrease in mRNAs expression of surfactant, including surfactant protein (SP)-A, SP-B, SP-C, and SP-D. SiO2NPs induced the L2 cell apoptosis. The increases in annexin V fluorescence, caspase-3 activity, and protein expression of cleaved-poly (ADP-ribose) polymerase (PARP), cleaved-caspase-9, and cleaved-caspase-7 were observed. The SiO2NPs induced caspase-3 activity was reversed by pretreatment of caspase-3 inhibitor Z-DEVD-FMK. SiO2NPs exposure increased reactive oxygen species (ROS) production, decreased mitochondrial transmembrane potential, and decreased protein and mRNA expression of Bcl-2 in L2 cells. SiO2NPs increased protein expression of cytosolic cytochrome c and Bax, and mRNAs expression of Bid, Bak, and Bax. SiO2NPs could induce the endoplasmic reticulum (ER) stress-related signals, including the increase in CHOP, XBP-1, and phospho-eIF2α protein expressions, and the decrease in pro-caspase-12 protein expression. SiO2NPs increased phosphoinositide 3-kinase (PI3K) activity and AKT phosphorylation. Both ROS inhibitor N-acetyl-l-cysteine (NAC) and PI3K inhibitor LY294002 reversed SiO2NPs-induced signals described above. However, the LY294002 could not inhibit SiO2NPs-induced ROS generation. These findings demonstrated first time that SiO2NPs induced L2 cell apoptosis through ROS-regulated PI3K/AKT signaling and its downstream mitochondria- and ER stress-dependent signaling pathways. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/32555254/Ultrafine_silicon_dioxide_nanoparticles_cause_lung_epithelial_cells_apoptosis_via_oxidative_stress_activated_PI3K/Akt_mediated_mitochondria__and_endoplasmic_reticulum_stress_dependent_signaling_pathways_ DB - PRIME DP - Unbound Medicine ER -