Characterization of the proteome and lipidome profiles of human lung cells after low dose and chronic exposure to multiwalled carbon nanotubes

Phuyal, Santosh; Kasem, Mayes; Knittelfelder, Oskar; Sharma, Animesh; Fonseca, Davi de Miranda; Vebraite, Vaineta; Shaposhnikov, Sergey; Slupphaug, Geir; Skaug, Vidar; Zienolddiny, Shanbeh

doi:10.1080/17435390.2018.1425500

Cited by 22 publications

(11 citation statements)

References 72 publications

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“…Critically short telomers result in activation of DNA damage response proteins, such as the phosphorylated forms of ataxia telangiectasia mutated (ATM), H2A histone family member X (H2A.X), and RAD17 checkpoint clamp loader component (RAD17) [ 34 ]. While many studies have shown that exposure to MWCNT leads to increased levels of DNA strand breaks and increased DNA repair activity and DNA damage [ 9 , 19 , 25 ], other studies did not observe genotoxicity following MWCNT-exposure [ 5 , 35 , 36 ]. In this study, we did not observe a regulation of genes involved in DNA damage or repair (i.e., ATM , ATR , RAD17 , NIEL3 , XPA , ALKBH1 , ALKBH5 , or OGG1 ) in HBEC-3KT cells exposed to NM-401.…”

Section: Discussionmentioning

confidence: 99%

Multiwalled Carbon Nanotubes Induce Fibrosis and Telomere Length Alterations

Alswady-Hoff

Erdem

Aleksandersen

et al. 2022

IJMS

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Telomere shortening can result in cellular senescence and in increased level of genome instability, which are key events in numerous of cancer types. Despite this, few studies have focused on the effect of nanomaterial exposure on telomere length as a possible mechanism involved in nanomaterial-induced carcinogenesis. In this study, effects of exposure to multiwalled carbon nanotubes (MWCNT) on telomere length were investigated in mice exposed by intrapleural injection, as well as in human lung epithelial and mesothelial cell lines. In addition, cell cycle, apoptosis, and regulation of genes involved in DNA damage repair were assessed. Exposure to MWCNT led to severe fibrosis, infiltration of inflammatory cells in pleura, and mesothelial cell hyperplasia. These histological alterations were accompanied by deregulation of genes involved in fibrosis and immune cell recruitment, as well as a significant shortening of telomeres in the pleura and the lung. Assessment of key carcinogenic mechanisms in vitro confirmed that long-term exposure to the long MWCNT led to a prominent telomere shortening in epithelial cells, which coincided with G1-phase arrest and enhanced apoptosis. Altogether, our data show that telomere shortening resulting in cell cycle arrest and apoptosis may be an important mechanism in long MWCNT-induced inflammation and fibrosis.

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Section: Discussionmentioning

confidence: 99%

Multiwalled Carbon Nanotubes Induce Fibrosis and Telomere Length Alterations

Alswady-Hoff

Erdem

Aleksandersen

et al. 2022

IJMS

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“…These pathways are mostly related to processes such as cellular proliferation, immune response, inflammation, amino acid‐dependent cell signaling, and secretion of organic electrolytes. For example, pathway analysis revealed perturbations in aminoacyl‐t‐RNA biosynthesis, further suggesting that there is a significant change in amino acid and protein metabolism (Phuyal et al, 2018). In agreement with these findings, effects of MWCNTs evidenced by other research also indicate similar cellular processes and responses related to toxicity.…”

Section: Discussionmentioning

confidence: 99%

Intravenous administration of three multiwalled carbon nanotubes to female rats and their effect on urinary biochemical profile

Mortensen

Snyder

Pathmasiri

et al. 2021

J of Applied Toxicology

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This study was conducted to investigate the influence of outer diameter (OD) and length (L) of multiwalled carbon nanotubes (MWCNTs) on biodistribution and the perturbation of endogenous metabolite profiles. Three different‐sized carboxylated MWCNTs (NIEHS‐12‐2: L 0.5–2 μm, OD 10–20 nm, NIEHS‐13‐2: L 0.5–2 μm, OD 30–50 nm, and NIEHS‐14‐2: L 10–30 μm, OD 10–20 nm) in water were administered to female Sprague‐Dawley rats as a single intravenous dose of 1 mg/kg MWCNTs. Biodistribution in liver, lung, spleen, and lymph nodes was evaluated in tissue sections at 1 and 7 days' post‐dosing using enhanced darkfield microscopy and hyperspectral imaging. Nuclear magnetic resonance (NMR) analysis was used for biochemical profiling and pathway mapping of endogenous metabolites in urine collected at 24‐h intervals prior to dosing, at Day 1 and Day 7. At Day 1 and Day 7, all three MWCNTs were observed in liver. NIEHS‐12‐2 was observed in spleen, whereas NIEHS‐13‐2 and NIEHS‐14‐2 were not. All three MWCNTs were observed in lymph nodes and lung at Day 7. The urinary biochemical profile showed the highest positive fold change (FC) at Day 7 for the metabolites acetate, alanine, and lactate, whereas 1‐methylnicotinamide, 2‐oxoglutarate, and hippurate had some of the lowest FCs for all three MWCNTs. This study demonstrates that the observed tissue location of MWCNTs is size dependent. Overlaps in the perturbation of endogenous metabolite profiles were found regardless of their size, and the biochemical responses were more profound at Day 7 compared with Day 1, indicating a delayed biological response to MWCNTs.

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“…As such, biocompatible NPs should not disrupt lipid homeostasis. For example, CNTs have been shown to induce lipid accumulation in different models, which could be related with the toxic effects of CNTs (Phuyal et al, 2018; H. Yang et al, 2019; T. Yang et al, 2020; H.‐Y. Zhang, Chen, Shao, Wang, & Liu, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…However, recent studies also suggested a role of ECs in lipid metabolism that disturbance of lipid droplet biogenesis could impair the function of ECs leading to disease development (Jung et al, 2020; Pacia et al, 2020). Interestingly, exposure to NMs disrupted lipid homeostasis in many types of cells, such as neurons (Bramini et al, 2019), bronchial epithelial cells (Phuyal et al, 2018), liver cells (Almansour, Sajti, Melhim, & Jarrar, 2016), vascular smooth muscle cells (H. Yang, Li, Yang, Liu, & Cao, 2019), and macrophages (Luo, Peng, Huang, & Cao, 2020), indicating that changes in lipid profiles are common outcomes following exposure to toxic NMs. But to the best of our knowledge, whether zirconia NPs will alter lipid profiles in ECs has not been investigated before.…”

Section: Introductionmentioning

confidence: 99%

Changes of lipid profiles in human umbilical vein endothelial cells exposed to zirconia nanoparticles with or without the presence of free fatty acids

Cheng

Guo

Xian

et al. 2020

J of Applied Toxicology

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Zirconia nanoparticles (NPs) have been widely used in biomedicine, which will likely lead to their interactions with endothelial cells (ECs). However, the toxicity of zirconia NPs to ECs is less investigated and the toxicological data are not consistent. Furthermore, no previous study, to the best of our knowledge, investigated the influence of zirconia NPs on lipid metabolism. This study investigated lipid profiles in human umbilical vein ECs (HUVECs) exposed to zirconia NPs with or without the presence of free fatty acids (FFAs). Incubation with FFA changed the hydrodynamic size, zeta potential, and surface profiles of zirconia NPs, indicating the surface coating effects. Exposure of HUVECs to various concentrations of zirconia NPs with or without the presence of FFA did not significantly decrease cellular viability, but FFA decreased zirconium elemental levels in NP‐exposed cells. Oil Red O staining showed that FFA or zirconia NPs and FFA, but not zirconia NPs alone, significantly increased lipid accumulation in HUVECs. Consistently, lipidomic data suggested that exposure to FFA or zirconia NPs and FFA up‐regulated most lipid classes in HUVECs. As the mechanisms for increased lipid accumulation, exposure to FFA or zirconia NPs and FFA up‐regulated endoplasmic reticulum (ER) stress axis IRE1α–XBP‐1, leading to increased FASN and ACSL3, proteins involved in lipid metabolism. Combined, our results demonstrated that zirconia NPs were noncytotoxic and showed minimal impact on ER stress‐mediated lipid metabolism in HUVECs under both normal and FFA‐challenged conditions, which indicated the relatively high biocompatibility of zirconia NPs to ECs.

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Characterization of the proteome and lipidome profiles of human lung cells after low dose and chronic exposure to multiwalled carbon nanotubes

Abstract: 2018) Characterization of the proteome and lipidome profiles of human lung cells after low dose and chronic exposure to multiwalled carbon nanotubes, Nanotoxicology, 12:2, 138-152,

Cited by 22 publications

References 72 publications

Multiwalled Carbon Nanotubes Induce Fibrosis and Telomere Length Alterations

Multiwalled Carbon Nanotubes Induce Fibrosis and Telomere Length Alterations

Intravenous administration of three multiwalled carbon nanotubes to female rats and their effect on urinary biochemical profile

Changes of lipid profiles in human umbilical vein endothelial cells exposed to zirconia nanoparticles with or without the presence of free fatty acids

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