Titanium Dioxide Nanoparticles Induce Endoplasmic Reticulum Stress-Mediated Autophagic Cell Death via Mitochondria-Associated Endoplasmic Reticulum Membrane Disruption in Normal Lung Cells

Yu, Kyeong-Nam; Chang, Simyung; Park, Soo‐Jin; Lim, Joohyun; Lee, Jin-Kyu; Yoon, Tae‐Jong; Kim, Jun-Sung; Cho, Myung‐Haing

doi:10.1371/journal.pone.0131208

Cited by 90 publications

(61 citation statements)

References 50 publications

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“…Recent studies report the endoplasmic reticulum stress (ER stress) as a common response in NPs related toxicity with studies on TiO 2 NPs (Zhang et al 2012, Chen et al 2014, Yu, Chang, et al 2015. The endoplasmic reticulum (ER) is an important organelle, which plays a role in folding and assembling of cellular proteins, in synthesis of lipids and sterols, and in regulating the balance of the intracellular calcium homeostasis, processes which are all dependent on the ER internal homeostasis.…”

Section: Introductionmentioning

confidence: 99%

In situquantification of diverse titanium dioxide nanoparticles unveils selective endoplasmic reticulum stress-dependent toxicity

et al. 2017

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Section: Introductionmentioning

confidence: 99%

In situquantification of diverse titanium dioxide nanoparticles unveils selective endoplasmic reticulum stress-dependent toxicity

et al. 2017

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“…15 Remarkably, autophagy has been discovered in cells exposed to TNPs. 20,21,[24][25][26] However, the underlying mechanistic insights into autophagy induced by TNPs are still poorly investigated. Recently, there is growing interest in the topic of how epigenetic processes modulate cellular behavior in response to environmental chemicals.…”

Section: Discussionmentioning

confidence: 99%

“…19,20 Autophagy, therefore, serves as a natural and essential defense mechanism against inflammatory, infectious, neurodegenerative, and neoplastic disorders, and deregulation of this pathway has been implicated in the pathogenesis of numerous human diseases. [21][22][23][24] Activation of autophagy was considered as an attempt for a cell to maintain cellular homeostasis by sequestering and degrading exogenous materials entered into the cytoplasm. However, the toxicological consequence of autophagy dysfunction is regarded as a potential mechanism of cell death.…”

Section: Introductionmentioning

confidence: 99%

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Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells

Bai¹,

Chen²,

Sun³

et al. 2016

IJN

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Titanium dioxide (TiO 2 ) nanoparticles (TNPs) are manufactured worldwide for a wide range of applications and the toxic effect of TNPs on biological systems is gaining attention. Autophagy is recognized as an emerging toxicity mechanism triggered by nanomaterials. MicroRNA 34a (miR34a) acts as a tumor suppressor gene by targeting many oncogenes, but how it affects autophagy induced by TNPs is not completely understood. Here, we observed the activation of TNP-induced autophagy through monodansylcadaverine staining and LC3-I/LC3-II conversion. Meanwhile, the transmission electron microscope ultrastructural analysis showed typical morphological characteristics in autophagy process. We detected the expression of miR34a and B-cell lymphoma/leukemia-2 (Bcl-2). In addition, the underlying mechanism of TNP-induced autophagy was performed using overexpression of miR34a by lentivirus vector transfection. Results showed that TNPs induced autophagy generation evidently. Typical morphological changes in the process of autophagy were observed by the transmission electron microscope ultrastructural analysis and LC3-I/LC3-II conversion increased significantly in TNP-treated cells. Meanwhile, TNPs induced the downregulation of miR34a and increased the expression of Bcl-2. Furthermore, overexpressed miR34a decreased the expression of Bcl-2 both in messenger RNA and protein level, following which the level of autophagy and cell death rate increased after the transfected cells were incubated with TNPs for 24 hours. These findings provide the first evidence that overexpressed miR34a enhanced TNP-induced autophagy and cell death through targeted downregulation of Bcl-2 in BEAS-2B cells.

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“…LC3 is one of the key regulators of autophagy, which is measured quantitatively by the ratio of LC3 II to LC3 I. The results clearly demonstrate that the LC3 II/LC3 I ratio increased significantly in the TiO 2 NP treated cells and the TiO 2 NP induces autophagy in human bronchial epithelial cells [62]. In addition, WenlinBai reported that over expressed miR34a enhanced TNP induced autophagy and cell death through targeted down regulation of Bcl 2 in BEAS 2B cells [50].…”

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confidence: 81%

The Role of Cell Autophagy in Toxicity Caused by Dental Nanomaterials

Wei¹

2017

NTMB

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NanomaterialsThe overview of nanomaterials Nanomaterials are defined as materials composed of unbound particles or particles in an aggregate or agglomerate state with one or more external dimensions with a size ranging from 1nm to 100nm [1]. Nanomaterials have a lot of free surfaces and interfaces and there is interaction between the various units. Based on the above characteristics, nanomaterials are featured by surface effect, small size effect, quantum size effect, macroscopic quantum tunneling effect and the dielectric confinement effect. Nanoparticles have lots of unpaired atoms, large specific surface area, less surface defects and can occur in conjunction with the polymer stronger physically or chemically. Added to the polymer material, they can improve the ductility, toughness, strength, barrier properties, heat resistance and dimensional stability of the material. They have been widely used in conventional materials, medical equipment, electronic equipment, paint and other industries. However, nanomaterials will affect the organism and produce a series of toxic effects by inducing oxidative stress and inflammatory response mechanisms in the cell, subcellular and protein levels. The nanomaterials commonly used in dentistryNanometer materials are widely applied in the field of dentistry, including dental restoration, antibacterial, caries treatment, orthodontic, root canal, bonding systems and so on.Adding nanoparticles to dental restoration materials to improve the performance has been widely used in the clinical field. In view of its unpaired atoms, large specific surface area, less surface defects and occurring in conjunction with the polymer either stronger physically or chemically, the novel resin composite exhibited a strong antibacterial property upon the addition of up to 5% nano antibacterial inorganic fillers, there by leading to effective caries inhibition in dental application [2]. The mesoporous silica biomaterials have great potential for serving as both a catalyst and carrier in the repair or regeneration of dental hard tissue [3]. Diatomite-based nanocomposite ceramics are good potential candidates for ceramic-based dental materials [4]. Nano silicon dioxide can also give polymers the characteristics of better viscosity, thermal stability, high strength, less volume shrinkage and of course, durability [5].In clinical endodontics especially root canal and restorative treatments we can see the near future potential of nanoparticles from the application of nanoparticles in the form of solutions for irrigation, medication and as an additive within sealers/restorative materials [6]. GICs can be applied to base plates of Orthodontic and modified denture base well, as which contain chlorhexidine hexametaphosphate nanoparticles and characterize the nanoparticle size shows a stronger antimicrobial activity [7].As for caries treatment, Hannig M said that Analysis of in vitro data indicates that apatite nanoparticles might be effective in reversing lesion progression in the outer but not in the deepe...

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Titanium Dioxide Nanoparticles Induce Endoplasmic Reticulum Stress-Mediated Autophagic Cell Death via Mitochondria-Associated Endoplasmic Reticulum Membrane Disruption in Normal Lung Cells

Cited by 90 publications

References 50 publications

In situquantification of diverse titanium dioxide nanoparticles unveils selective endoplasmic reticulum stress-dependent toxicity

In situquantification of diverse titanium dioxide nanoparticles unveils selective endoplasmic reticulum stress-dependent toxicity

Downregulation of B-cell lymphoma/leukemia-2 by overexpressed microRNA 34a enhanced titanium dioxide nanoparticle-induced autophagy in BEAS-2B cells

The Role of Cell Autophagy in Toxicity Caused by Dental Nanomaterials

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