Titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling
Abstract Background Epidemiological emerging evidence shows that human exposure to some nanosized materials present in the environment would contribute to the onset and/or progression of Alzheimer’s disease (AD). The cellular and molecular mechanisms whereby nanoparticles would exert some adverse ef...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-07-01
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| Series: | Particle and Fibre Toxicology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12989-022-00490-x |
| _version_ | 1828541579114053632 |
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| author | Luiz W. Ribeiro Mathéa Pietri Hector Ardila-Osorio Anne Baudry François Boudet-Devaud Chloé Bizingre Zaira E. Arellano-Anaya Anne-Marie Haeberlé Nicolas Gadot Sonja Boland Stéphanie Devineau Yannick Bailly Odile Kellermann Anna Bencsik Benoit Schneider |
| author_facet | Luiz W. Ribeiro Mathéa Pietri Hector Ardila-Osorio Anne Baudry François Boudet-Devaud Chloé Bizingre Zaira E. Arellano-Anaya Anne-Marie Haeberlé Nicolas Gadot Sonja Boland Stéphanie Devineau Yannick Bailly Odile Kellermann Anna Bencsik Benoit Schneider |
| author_sort | Luiz W. Ribeiro |
| collection | DOAJ |
| description | Abstract Background Epidemiological emerging evidence shows that human exposure to some nanosized materials present in the environment would contribute to the onset and/or progression of Alzheimer’s disease (AD). The cellular and molecular mechanisms whereby nanoparticles would exert some adverse effects towards neurons and take part in AD pathology are nevertheless unknown. Results Here, we provide the prime evidence that titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) bind the cellular form of the prion protein (PrPC), a plasma membrane protein well known for its implication in prion diseases and prion-like diseases, such as AD. The interaction between TiO2- or CB-NPs and PrPC at the surface of neuronal cells grown in culture corrupts PrPC signaling function. This triggers PrPC-dependent activation of NADPH oxidase and subsequent production of reactive oxygen species (ROS) that alters redox equilibrium. Through PrPC interaction, NPs also promote the activation of 3-phosphoinositide-dependent kinase 1 (PDK1), which in turn provokes the internalization of the neuroprotective TACE α-secretase. This diverts TACE cleavage activity away from (i) TNFα receptors (TNFR), whose accumulation at the plasma membrane augments the vulnerability of NP-exposed neuronal cells to TNFα -associated inflammation, and (ii) the amyloid precursor protein APP, leading to overproduction of neurotoxic amyloid Aβ40/42 peptides. The silencing of PrPC or the pharmacological inhibition of PDK1 protects neuronal cells from TiO2- and CB-NPs effects regarding ROS production, TNFα hypersensitivity, and Aβ rise. Finally, we show that dysregulation of the PrPC-PDK1-TACE pathway likely occurs in the brain of mice injected with TiO2-NPs by the intra-cerebro-ventricular route as we monitor a rise of TNFR at the cell surface of several groups of neurons located in distinct brain areas. Conclusion Our in vitro and in vivo study thus posits for the first time normal cellular prion protein PrPC as being a neuronal receptor of TiO2- and CB-NPs and identifies PrPC-coupled signaling pathways by which those nanoparticles alter redox equilibrium, augment the intrinsic sensitivity of neurons to neuroinflammation, and provoke a rise of Aβ peptides. By identifying signaling cascades dysregulated by TiO2- and CB-NPs in neurons, our data shed light on how human exposure to some NPs might be related to AD. |
| first_indexed | 2024-12-12T01:41:58Z |
| format | Article |
| id | doaj.art-39138cafd6da479a9d8511efe7d61aa2 |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-12-12T01:41:58Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj.art-39138cafd6da479a9d8511efe7d61aa22022-12-22T00:42:40ZengBMCParticle and Fibre Toxicology1743-89772022-07-0119112210.1186/s12989-022-00490-xTitanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signalingLuiz W. Ribeiro0Mathéa Pietri1Hector Ardila-Osorio2Anne Baudry3François Boudet-Devaud4Chloé Bizingre5Zaira E. Arellano-Anaya6Anne-Marie Haeberlé7Nicolas Gadot8Sonja Boland9Stéphanie Devineau10Yannick Bailly11Odile Kellermann12Anna Bencsik13Benoit Schneider14INSERM, UMR-S 1124INSERM, UMR-S 1124INSERM, UMR-S 1124INSERM, UMR-S 1124INSERM, UMR-S 1124INSERM, UMR-S 1124INSERM, UMR-S 1124Institut Des Neurosciences Cellulaires Et Intégratives, CNRS UPR 3212, Université de StrasbourgPlateforme Anatomopathologie Recherche, INSERM 1052, CNRS 5286, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1, Université de LyonCNRS UMR 8251, Unité de Biologie Fonctionnelle Et Adaptative, Université Paris CitéCNRS UMR 8251, Unité de Biologie Fonctionnelle Et Adaptative, Université Paris CitéInstitut Des Neurosciences Cellulaires Et Intégratives, CNRS UPR 3212, Université de StrasbourgINSERM, UMR-S 1124ANSES Laboratoire de Lyon, French Agency for Food, Environmental and Occupational Health & Safety (ANSES), Université Claude Bernard Lyon 1INSERM, UMR-S 1124Abstract Background Epidemiological emerging evidence shows that human exposure to some nanosized materials present in the environment would contribute to the onset and/or progression of Alzheimer’s disease (AD). The cellular and molecular mechanisms whereby nanoparticles would exert some adverse effects towards neurons and take part in AD pathology are nevertheless unknown. Results Here, we provide the prime evidence that titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) bind the cellular form of the prion protein (PrPC), a plasma membrane protein well known for its implication in prion diseases and prion-like diseases, such as AD. The interaction between TiO2- or CB-NPs and PrPC at the surface of neuronal cells grown in culture corrupts PrPC signaling function. This triggers PrPC-dependent activation of NADPH oxidase and subsequent production of reactive oxygen species (ROS) that alters redox equilibrium. Through PrPC interaction, NPs also promote the activation of 3-phosphoinositide-dependent kinase 1 (PDK1), which in turn provokes the internalization of the neuroprotective TACE α-secretase. This diverts TACE cleavage activity away from (i) TNFα receptors (TNFR), whose accumulation at the plasma membrane augments the vulnerability of NP-exposed neuronal cells to TNFα -associated inflammation, and (ii) the amyloid precursor protein APP, leading to overproduction of neurotoxic amyloid Aβ40/42 peptides. The silencing of PrPC or the pharmacological inhibition of PDK1 protects neuronal cells from TiO2- and CB-NPs effects regarding ROS production, TNFα hypersensitivity, and Aβ rise. Finally, we show that dysregulation of the PrPC-PDK1-TACE pathway likely occurs in the brain of mice injected with TiO2-NPs by the intra-cerebro-ventricular route as we monitor a rise of TNFR at the cell surface of several groups of neurons located in distinct brain areas. Conclusion Our in vitro and in vivo study thus posits for the first time normal cellular prion protein PrPC as being a neuronal receptor of TiO2- and CB-NPs and identifies PrPC-coupled signaling pathways by which those nanoparticles alter redox equilibrium, augment the intrinsic sensitivity of neurons to neuroinflammation, and provoke a rise of Aβ peptides. By identifying signaling cascades dysregulated by TiO2- and CB-NPs in neurons, our data shed light on how human exposure to some NPs might be related to AD.https://doi.org/10.1186/s12989-022-00490-xNanoparticlesPrPC receptorSignalingTNFα receptorsAβ peptidesNeuroinflammation |
| spellingShingle | Luiz W. Ribeiro Mathéa Pietri Hector Ardila-Osorio Anne Baudry François Boudet-Devaud Chloé Bizingre Zaira E. Arellano-Anaya Anne-Marie Haeberlé Nicolas Gadot Sonja Boland Stéphanie Devineau Yannick Bailly Odile Kellermann Anna Bencsik Benoit Schneider Titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling Particle and Fibre Toxicology Nanoparticles PrPC receptor Signaling TNFα receptors Aβ peptides Neuroinflammation |
| title | Titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling |
| title_full | Titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling |
| title_fullStr | Titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling |
| title_full_unstemmed | Titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling |
| title_short | Titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling |
| title_sort | titanium dioxide and carbon black nanoparticles disrupt neuronal homeostasis via excessive activation of cellular prion protein signaling |
| topic | Nanoparticles PrPC receptor Signaling TNFα receptors Aβ peptides Neuroinflammation |
| url | https://doi.org/10.1186/s12989-022-00490-x |
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