Multi-walled carbon nanotubes decrease neuronal NO synthase in 3D brain organoids

Jiang, Ying; Gong, Housheng; Jiang, Shaohua; She, Chao-Wen; Cao, Yi

doi:10.1016/j.scitotenv.2020.141384

Cited by 37 publications

(25 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recent studies also that NMs could affect KLF proteins in different models. For example, carbon nanotubes were shown to alter KLF proteins in ECs (B. Wu et al, 2020), vascular smooth muscle cells (Li, Yang, et al, 2019), and 3‐D brain organoids (Jiang, Gong, Jiang, She, & Cao, 2020). Titanate fibers down‐regulated KLF2 proteins leading to decreased NO production in an endothelium model developed by using cell culture inserts (Li, Zheng, et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Toxicity evaluation of mesoporous silica particles Santa Barbara No. 15 amorphous in human umbilical vein endothelial cells: influence of particle morphology

Teng¹,

Yang²,

Wang³

et al. 2021

J of Applied Toxicology

View full text Add to dashboard Cite

Morphology plays a vital role in determining the biological effects of silica nanoparticles (NPs), but its influence on the toxicity of silica NPs in endothelial cells (ECs) is still inconclusive. We synthesized five kinds of Santa Barbara 15 amorphous (SBA‐15) particles with different shapes and added them to human umbilical vein endothelial cells (HUVEC). After 24 After incubation and treatment with 100 ml, more than 80% of the cells are still alive. The microgram/ml of SBA‐15 indicates that SBA‐15 has high biocompatibility. Fibrous SBA‐15 (5) leads to the highest Si element concentration in HUVEC. No NP reduces the release of NO, and NO is an important signaling molecule in the vascular system. Only the aggregated spherical SBA‐15 (3) will moderately reduce the endothelial nitric oxide synthase (eNOS) protein. Regarding transcription factors regulating eNOS, we found that all SBA‐15 types significantly increased Kruppel‐like factor 2 (KLF2) protein, irregular SBA‐15 (1), non‐aggregated spherical SBA‐15 (2) and aggregation The spherical SBA‐15 (3) greatly reduces KLF4 by more than 50%. Overall, our results indicate that SBA‐15 with different morphologies can be internalized into HUVEC and only cause moderate cytotoxicity. All silica NPs have the smallest effect on the NO‐eNOS pathway, but the irregular spherical SBA‐15 reduces the eNOS modifier KLF4. The rod‐shaped SBA‐15 (4) seems to have higher biocompatibility because they are internalized and have negligible adverse effects on HUVEC. These results provide new evidence for the toxic effects of different forms of silica nanoparticles on HUVEC.

show abstract

Section: Discussionmentioning

confidence: 99%

Toxicity evaluation of mesoporous silica particles Santa Barbara No. 15 amorphous in human umbilical vein endothelial cells: influence of particle morphology

Teng¹,

Yang²,

Wang³

et al. 2021

J of Applied Toxicology

View full text Add to dashboard Cite

show abstract

“…However, we also noticed that MWCNTs and to less extent HNTs increased KLF2 proteins, and we suggested this observation as a protective mechanism (B. Wu et al, 2020). The influence of MWCNTs on KLF4‐NOS pathway has also been verified in advanced in vitro model, such as brain organoids (Jiang et al, 2020).…”

Section: The Potential Roles Of Klfs In Nm‐induced Adverse Vascular Effectsmentioning

confidence: 92%

Potential roles of Kruppel‐like factors in mediating adverse vascular effects of nanomaterials: A review

Cao

2021

J of Applied Toxicology

Self Cite

View full text Add to dashboard Cite

The development of nanotechnology leads to the exposure of human beings to nanomaterials (NMs), and there is a health concern about the adverse vascular effects of NMs. Current data from epidemiology, controlled human exposure, and animal studies suggested that exposure to NMs could induce cardiopulmonary effects. In support of in vivo findings, in vitro studies showed that direct contact of vascular cells with NMs could induce endothelial cell (EC) activation and promote macrophage foam cell formation, although only limited studies showed that NMs could damage vascular smooth muscle cells and promote their phenotypic switch. It has been proposed that NMs induced adverse vascular effects via different mechanisms, but it is still necessary to understand the upstream events. Kruppel‐like factors (KLFs) are a set of C2H2 zinc finger transcription factors (TFs) that can regulate various aspects of vascular biology, but currently, the roles of KLF2 in mediating the adverse vascular effects of NMs have gained little attention by toxicologists. This review summarized current knowledge about the adverse vascular effects of NMs and proposed the potential roles of KLFs in mediating these effects based on available data from toxicological studies as well as the current understanding about KLFs in vascular biology. Finally, the challenges in investigating the role of KLFs in vascular toxicology were also summarized. Considering the important roles of KLFs in vascular biology, further studies are needed to understand the influence of NMs on KLFs and the downstream events.

show abstract

“…The 3D brain organoids were obtained after 90 days of differentiation and maintained in human 3D cerebral organoid medium per manufacturer's instructions (Hopstem Biotechnology Co. Ltd., China). As described previously (Jiang et al 2020), we used fluorescent immunohistochemical staining to analyze the following markers of cortical layers: T-box brain protein 1 (TBR1, for cortical layers I, V, and VI), brain-2 (BRN2) and special AT-rich sequence-binding protein 2 (SATB2, for cortical layers II-IV), and chicken ovalbumin upstream promoter-transcription factor-interacting protein 2 (CTIP2; for layers V and VI). Marker staining in all samples was verified by light microscopy with an Axio Observer3 (Carl Zeiss).…”

Section: Three-dimensional Brain Organoid Generation and Characterizationmentioning

confidence: 99%

“…To determine superoxide levels, the 3D brain organoids were incubated with various concentrations of ZnO NPs for 24 h, after which superoxide levels were measured in each cell by using DHE staining (Sigma-Aldrich, USA) as described elsewhere (Jiang et al 2020). All samples were counted and evaluated by using a NucleoCounter NC-3000.…”

Section: Superoxide Determinationmentioning

confidence: 99%

“…Even brain organoids derived from non-human primates differ significantly from human brain organoids (Pollen et al 2019), and thus presumably brain organoids based on mouse stem cells probably also differ substantially from those based on human stem cells. We recently used 3D brain organoids based on human iPSC to test the effects of multi-walled carbon nanotubes (MWCNTs) on nitric oxide (NO) signaling pathways in brains (Jiang et al 2020). Huang et al recently utilized 3D brain organoids based on human embryonic stem cells to evaluate cadmium-induced neurodevelopmental toxicity (Huang et al 2021).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The cytotoxicity of zinc oxide nanoparticles to 3D brain organoids results from excessive intracellular zinc ions and defective autophagy

et al. 2021

Self Cite

View full text Add to dashboard Cite

Cytotoxicity caused by high levels of ZnO NPs (64 μg/mL) correlated with high intracellular Zn ion levels but not superoxide levels. Exposure to a noncytotoxic concentration of ZnO NPs (16 μg/mL) increased the autophagy-marker proteins LC3B-II/I but decreased p62 accumulation, whereas a cytotoxic concentration of ZnO NPs (64 μg/mL) decreased LC3B-II/I proteins but did not affect p62 accumulation. Fluorescence micro-optical sectioning tomography revealed that 64 μg/mL ZnO NPs led to decreases in LC3B proteins that were more obvious at the outer layers of the organoids, which were directly exposed Abstract Although the neurotoxicity of ZnO nanoparticles (NPs) has been evaluated in animal and nerve cell culture models, these models cannot accurately mimic human brains. Three-dimensional (3D) brain organoids based on human-induced pluripotent stem cells have been developed to study the human brains, but this model has rarely been used to evaluate NP neurotoxicity. We used 3D brain organoids that express cortical layer proteins to investigate the mechanisms of ZnO NP-induced neurotoxicity.Liangliang Liu and Junkang Wang contributed equally to this work. Highlights 3D human brain organoids were used to evaluate neurotoxicity of ZnO NPs. ZnO NPs induced cytotoxicity by inducing intracellular Zn ions and defective autophagy. ZnO NPs decreased LC3B proteins and increased the appearance of micronuclei more obviously in the outlayers of organoids. Chemical inhibition of autophagy increased ZnO NPinduced cytotoxicity and intracellular Zn ions.

show abstract

Multi-walled carbon nanotubes decrease neuronal NO synthase in 3D brain organoids

Cited by 37 publications

References 59 publications

Toxicity evaluation of mesoporous silica particles Santa Barbara No. 15 amorphous in human umbilical vein endothelial cells: influence of particle morphology

Toxicity evaluation of mesoporous silica particles Santa Barbara No. 15 amorphous in human umbilical vein endothelial cells: influence of particle morphology

Potential roles of Kruppel‐like factors in mediating adverse vascular effects of nanomaterials: A review

The cytotoxicity of zinc oxide nanoparticles to 3D brain organoids results from excessive intracellular zinc ions and defective autophagy

Contact Info

Product

Resources

About