Ontogeny of Second Messenger Systems

Imam, Syed Z.; Rosas-Hernández, Héctor; Cuevas, Elvis; Lantz, Susan M.; Sarkar, Sumit; Ali, Syed F.; Paule, Merle G.

doi:10.1016/b978-0-12-809405-1.00017-1

Cited by 2 publications

(3 citation statements)

References 80 publications

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“…Gene cluster II showed enrichment for gene regulatory network associated with DNMT1 and DNMT3A, key players of DNA methylation dependent gene repression regulation that is known to mediate expression of synaptic plasticity genes in response to stress (Figure 5 D) (Feng et al, 2010;Moore et al, 2013;Bayraktar and Kreutz, 2018;Sun et al, 2020). We were able to detect activation of REST (miRNA) and DNA methylation dependent gene silencing mechanism which were previously established to be involved in TMT neurotoxicity (Imam et al, 2018;Kim et al, 2021).…”

Section: D Supplementary Table 6)mentioning

confidence: 62%

Neuro-toxicogenomic mapping of TMT induced neurotoxicity using human minibrain reveals associated adverse outcome events

Govindan

Alpern

Stoppini

et al. 2022

Preprint

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Genome-wide transcriptomic interrogation of organoids and 3D tissue models are increasingly used for characterizing drug, toxicity responses and neurodevelopmental disorders. We established here a neuro-toxicogenomic assay by utilizing 'minibrain', a human in vitro 3D brain model system and a low-cost, highly multiplexable RNA-seq methodology (BRB-seq) for screening the effect of trimethyltin chloride (TMT) induced neurotoxicity. We demonstrate that transcriptomic profiling is insightful to the cellular composition and regional identity of the minibrain. Further, we characterize the transcriptomic changes associated with the dose-time neurotoxic response of minibrain upon exposure to TMT. The distinct gene expression changes and molecular candidates identified with our pipeline provides insight to map the key events involved in the adverse outcome pathway of TMT associated neurotoxicity. We identify processes such as endoplasmic reticulum stress, dysregulation of synaptic genes and downregulation of neuron-morphology associated genes upon exposure to TMT. In response to TMT, we identify activation of an early response homeostatic mechanism in minibrain and an interplay of STAT pathways correlating with the dose severity. In this study, we present a neuro-toxicogenomic assay that demonstrates the power of a low-cost transcriptomic screening to study chemical induced neurotoxicity.

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Section: D Supplementary Table 6)mentioning

confidence: 62%

Neuro-toxicogenomic mapping of TMT induced neurotoxicity using human minibrain reveals associated adverse outcome events

Govindan

Alpern

Stoppini

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Further studies are needed to fully elucidate the composition and evolution of the protein corona of these SPIONs when in contact with the biological milieu. To define safe conditions of SPION exposure avoiding toxic effects, 4,14,16,19,46 cell viability was next assessed at both 14 and 21 DIV (Figure 2A and Figure S7). Viability in all culture conditions was found statistically similar to control cells without nanoparticles, except for the highest concentration of NFA (0.1 mg Fe mL −1 ), in which a significant reduction was identified (oneway ANOVA followed by Scheffétest, p < 0.001*** for all comparisons).…”

Section: Resultsmentioning

confidence: 99%

“…Regarding size, Imam et al found that SPIONs as small as 10 nm generated neuronal damage in SH-SY5Y cells (i.e., a cell line of neuroblastoma origin) after 24 h of exposure at a very low dose (0.01 mg mL −1 ). 14 These data already alerted us to the neurotoxic potential of some very small sized SPIONs and the higher susceptibility of neural cells to SPION-mediated toxicity mechanisms in comparison with other cell types. Considering that nanoparticle size is essential to ensure a desired magnetic performance, a compromise must be taken to maximize therapeutic outcomes.…”

Section: Introductionmentioning

confidence: 99%

Cellular and Molecular Processes Are Differently Influenced in Primary Neural Cells by Slight Changes in the Physicochemical Properties of Multicore Magnetic Nanoparticles

Benayas

Espinosa

Portolés

et al. 2023

ACS Appl. Mater. Interfaces

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Herein, we use two exemplary superparamagnetic iron oxide multicore nanoparticles (SPIONs) to illustrate the significant influence of slightly different physicochemical properties on the cellular and molecular processes that define SPION interplay with primary neural cells. Particularly, we have designed two different SPION structures, NFA (i.e., a denser multicore structure accompanied by a slightly less negative surface charge and a higher magnetic response) and NFD (i.e., a larger surface area and more negatively charged), and identified specific biological responses dependent on SPION type, concentration, exposure time, and magnetic actuation. Interestingly, NFA SPIONs display a higher cell uptake, likely driven by their less negative surface and smaller protein corona, more significantly impacting cell viability and complexity. The tight contact of both SPIONs with neural cell membranes results in the significant augmentation of phosphatidylcholine, phosphatidylserine, and sphingomyelin and the reduction of free fatty acids and triacylglycerides for both SPIONs. Nonetheless, NFD induces greater effects on lipids, especially under magnetic actuation, likely indicating a preferential membranal location and/or a tighter interaction with membrane lipids than NFA, in agreement with their lower cell uptake. From a functional perspective, these lipid changes correlate with an increase in plasma membrane fluidity, again larger for more negatively charged nanoparticles (NFD). Finally, the mRNA expression of iron-related genes such as Ireb-2 and Fth-1 remains unaltered, while TfR-1 is only detected in SPION-treated cells. Taken together, these results demonstrate the substantial impact that minor physicochemical differences of nanomaterials may exert in the specific targeting of cellular and molecular processes. A denser multicore structure generated by autoclave-based production is accompanied by a slight difference in surface charge and magnetic properties that become decisive for the biological impact of these SPIONs. Their capacity to markedly modify the lipidic cell content makes them attractive as lipid-targetable nanomedicines.

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Ontogeny of Second Messenger Systems

Cited by 2 publications

References 80 publications

Neuro-toxicogenomic mapping of TMT induced neurotoxicity using human minibrain reveals associated adverse outcome events

Neuro-toxicogenomic mapping of TMT induced neurotoxicity using human minibrain reveals associated adverse outcome events

Cellular and Molecular Processes Are Differently Influenced in Primary Neural Cells by Slight Changes in the Physicochemical Properties of Multicore Magnetic Nanoparticles

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