Size dependent effect of ZnO nanoparticles on endoplasmic reticulum stress signaling pathway in murine liver

Kuang, Huijuan; Yang, Pengfei; Yang, Lin; Aguilar, Zoraida P.; Xu, Hengyi

doi:10.1016/j.jhazmat.2016.05.063

Cited by 73 publications

(35 citation statements)

References 40 publications

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“…Yang et al [171] showed that hepatotoxicity of orally delivered ZnO NPs is mediated through an ER stress-mediated apoptotic signaling pathway and increased translation of related proteins in mice. In another study Kuang et al [172] reported that ER stressmediated apoptosis triggered by ZnO NPs is size dependent, and smaller ZnO NPs are more toxic than 90-nm ZnO NPs in murine liver.…”

Section: Nps Induce Er-mediated Apoptosismentioning

confidence: 99%

Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles

et al. 2018

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Nanomaterials have gained a rapid increase in use in a variety of applications that pertain to many aspects of human life. The majority of these innovations are centered on medical applications and a range of industrial and environmental uses ranging from electronics to environmental remediation. Despite the advantages of NPs, the knowledge of their toxicological behavior and their interactions with the cellular machinery that determines cell fate is extremely limited. This review is an attempt to summarize and increase our understanding of the mechanistic basis of nanomaterial interactions with the cellular machinery that governs cell fate and activity. We review the mechanisms of NP-induced necrosis, apoptosis and autophagy and potential implications of these pathways in nanomaterial-induced outcomes. Abbreviations: Ag, silver; CdTe, cadmium telluride; CNTs, carbon nanotubes; EC, endothelial cell; GFP, green fluorescent protein; GO, graphene oxide; GSH, glutathione; HUVECs, human umbilical vein endothelial cells; NP, nanoparticle; PEI, polyethylenimine; PVP, polyvinylpyrrolidone; QD, quantum dot; ROS, reactive oxygen species; SiO, silicon dioxide; SPIONs, superparamagnetic iron oxide nanoparticles; SWCNT, single-walled carbon nanotubes; TiO, titanium dioxide; USPION, ultra-small super paramagnetic iron oxide; ZnO, zinc oxide.

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Section: Nps Induce Er-mediated Apoptosismentioning

confidence: 99%

Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles

et al. 2018

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“…If NM‐induced ER stress is excessive and prolonged, the cell death pathway could be activated as a consequence (Cao et al, ). The linkage between ER stress and ZnO NM‐induced toxicity has been proved in human endothelial cells (Chen et al, ), human lung fibroblasts (Ng et al, ), Saccharomyces cerevisiae (Babele, Thakre, Kumawat, & Tomar, ) as well as mice livers (Kuang, Yang, Yang, Aguilar, & Xu, ; Yang et al, ). However, it should be noticed that in a complex biological microenvironment, ER stress might also be influenced by biological molecules (Hummasti & Hotamisligil, ).…”

Section: Introductionmentioning

confidence: 99%

Palmitate enhanced the cytotoxicity of ZnO nanomaterials possibly by promoting endoplasmic reticulum stress

Chen

Yang

Jiang

et al. 2019

J of Applied Toxicology

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We recently synthesized ZnO nanomaterials (denoted as ZnO nanorods [NRs] and Mini‐NRs) and suggested that their cytotoxicity could be related with the activation of endoplasmic reticulum (ER) stress apoptosis. However, in a complex biological microenvironment, the ER stress‐apoptosis pathway could also be modulated by biological molecules, such as free fatty acids, leading to unpredicted biological effects. In this study, we investigated the combined toxicity of ZnO NRs/Mini‐NRs and palmitate (PA) to THP‐1 macrophages. PA influenced the zeta potential and solubility of ZnO NRs and ZnO Mini‐NRs in water, which indicated a change of colloidal stability. Exposure to ZnO NRs and Mini‐NRs dose‐dependent decreased cellular viability and release of soluble monocyte chemotactic protein 1 (sMCP‐1), and these effects were significantly promoted with the presence of PA. However, ZnO NR‐ and Mini‐NR‐induced intracellular Zn ions or reactive oxygen species were not significantly affected by PA. ZnO NRs and ZnO Mini‐NRs significantly promoted the expression of ER stress genes HSPA5, DDIT3, XBP‐1s and apoptotic gene CASP3, whereas PA also modestly promoted the expression of HSPA5, DDIT3 and CASP3. Interestingly, the ER stress inducer thapsigargin showed a similar effect as PA to promote the cytotoxicity of ZnO NRs and ZnO Mini‐NRs. It is suggested that PA might promote the cytotoxicity of ZnO NRs and ZnO Mini‐NRs possibly by promoting ER stress.

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“…However, relatively few studies assessed the possible role of physicochemical properties in ZnO NP‐induced ER stress and toxicity. Indeed, only one study, to the best of our knowledge, showed size‐dependent activation of ER stress pathways and damage to livers in mice following long‐term ZnO NP gavage (Kuang, Yang, Yang, Aguilar, & Xu, ).…”

Section: Introductionmentioning

confidence: 99%

“…However, relatively few studies assessed the possible role of physicochemical properties in ZnO NP-induced ER stress and toxicity. Indeed, only one study, to the best of our knowledge, showed size-dependent activation of ER stress pathways and damage to livers in mice following long-term ZnO NP gavage (Kuang, Yang, Yang, Aguilar, & Xu, 2016 NMs was investigated by transmission electron microscope (TEM) as well as scanning transmission electron microscope (SEM), and crystallinity was determined by X-ray diffraction (XRD). The BET surface area, hydrodynamic size, zeta potential and polydispersity index (PDI) of ZnO NMs were also measured.…”

Section: Introductionmentioning

confidence: 99%

The toxicity of ZnO nanomaterials to HepG2 cells: the influence of size and shape of particles

Yan

Jiang

Liu

et al. 2018

J of Applied Toxicology

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Understanding the possible role of physicochemical properties in determining the toxicity of ZnO nanomaterials (NMs) is crucial for the safe use of ZnO-based materials. In this study, we synthesized four types of ZnO NMs, and characterized them as ZnO nanorods (NRs; length 400-500 nm, diameter 150-200 nm), ZnO Mini-NRs (length 50-100 nm, diameter 15-20 nm), amorphous ZnO microspheres (a-ZnO MS) and crystalline ZnO MS (c-ZnO MS; the a/c-ZnO MS are nanoflowers with an extensive growth of sheet-like structures). ZnO NMs and ZnO Mini-NRs were significantly more cytotoxic than a/c-ZnO MS, and this trend was similar in both HepG2 cells and human umbilical vein endothelial cells. Intracellular reactive oxygen species was only modestly induced by c-ZnO MS, whereas intracellular Zn ions were dose-dependently increased in HepG2 cells by the exposure of all types of ZnO NMs. The expression of endoplasmic reticulum stress marker DDIT3 was induced following an order of ZnO NRs > a-ZnO MS > c-ZnO MS > ZnO Mini-NRs, and the apoptosis gene CASP12 was induced following an order of a-ZnO MS > ZnO NRs > c-ZnO MS > ZnO Mini-NRs. Combined, these results suggested that ZnO NM-induced cytotoxicity and expression of endoplasmic reticulum stress-apoptosis genes could be influenced by the size and shape of ZnO NMs.

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Size dependent effect of ZnO nanoparticles on endoplasmic reticulum stress signaling pathway in murine liver

Cited by 73 publications

References 40 publications

Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles

Necrotic, apoptotic and autophagic cell fates triggered by nanoparticles

Palmitate enhanced the cytotoxicity of ZnO nanomaterials possibly by promoting endoplasmic reticulum stress

The toxicity of ZnO nanomaterials to HepG2 cells: the influence of size and shape of particles

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