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Perturbation of intestinal stem cell homeostasis and radiation enteritis recovery via dietary titanium dioxide nanoparticles.

ABSTRACT: Small intestinal health and enteritis incidence are tightly coupled to the homeostasis of intestinal stem cells (ISCs), which are sensitive to dietary alterations. However, little is known about the impact of food additives on ISC pool. Here, we demonstrate that chronic exposure to low-dose TiO₂ NPs, a commonly used food additive, significantly hampers primary human and mouse ISC-derived organoid formation and growth by specifically attenuating Wnt signal transduction. Mechanistically, TiO₂ NPs alter the endocytic trafficking of the Wnt receptor LRP6 and prevent the nuclear entry of β-catenin. Notably, dietary TiO₂ NPs elicit modest chronic stress in healthy intestines and considerably impede the recovery of radiation enteritis by perturbing the homeostasis of ISCs in vivo. Our results identify a health concern of TiO₂ NP exposure on ISC homeostasis and radiation enteritis recovery. These findings suggest extra precaution during the treatment of radiation enteritis and provide new insights into food additive-ISC interaction.

SUBMITTER: Zhang L

PROVIDER: S-EPMC10392070 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Perturbation of intestinal stem cell homeostasis and radiation enteritis recovery via dietary titanium dioxide nanoparticles.

Zhang Linpei L He Yinli Y Dong Lele L Liu Chang C Su Lin L Guo Ruirui R Luo Qinying Q Gan Baoyu B Cao Fang F Wang Yawen Y Song Haiyun H Li Xiaojiao X

Cell proliferation 20230216 8

Small intestinal health and enteritis incidence are tightly coupled to the homeostasis of intestinal stem cells (ISCs), which are sensitive to dietary alterations. However, little is known about the impact of food additives on ISC pool. Here, we demonstrate that chronic exposure to low-dose TiO<sub>2</sub> NPs, a commonly used food additive, significantly hampers primary human and mouse ISC-derived organoid formation and growth by specifically attenuating Wnt signal transduction. Mechanistically ...[more]

PMID: 36798041

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Project description:BackgroundEpidemiological 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.ResultsHere, 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.ConclusionOur 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.

Dataset Information

Perturbation of intestinal stem cell homeostasis and radiation enteritis recovery via dietary titanium dioxide nanoparticles.

Publications

Perturbation of intestinal stem cell homeostasis and radiation enteritis recovery via dietary titanium dioxide nanoparticles.

Similar Datasets

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