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1.
Toxicology ; 461: 152898, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34403730

RESUMO

Silver nanoparticles (AgNPs) are widely used in medical and commercial products for their unique antibacterial functions. However, the impact of AgNPs on human neural development is not well understood. To investigate the effect of AgNPs on human neural development, various doses of 20 nm citrate-coated AgNP (AgSC) were administered to human embryonic stem cell derived neural progenitors during the neuronal differentiation. Immunofluorescence staining with neuronal progenitor markers SOX2 (sex determining region Y-box 2) and Nestin (VI intermediate filament protein) showed that AgSC inhibited rosette formation, neuronal progenitor proliferation, and neurite outgrowth. Furthermore, AgSC promoted astrocyte activation and neuronal apoptosis. These adverse effects can be partially recovered with ascorbic acid. A genome-wide transcriptome analysis of both AgSC treated and untreated samples indicated that the most up-graduated genes were a group of Metallothionein (1F, 1E, 2A) proteins, a metal-binding protein that plays an essential role in metal homeostasis, heavy metal detoxification, and cellular anti-oxidative defence. The most significantly down-regulated genes were neuronal differentiation 6 (NEUROD6) and fork head box G1 (FOXG1). GO analyse indicated that the regulation of cholesterol biosynthetic process, neuron differentiation, synapse organization and pattern specification, oliogenesis, and neuronal apoptosis were the most impacted biological processes. KEGG pathway analyse showed that the most significantly impacted pathways were C5 isoprenoid, axon guidance, Notch, WNT, RAS-MAPK signalling pathways, lysosome, and apoptosis. Our data suggests that AgSCs interfered with metal homeostasis and cholesterol biosynthesis which induced oxidative stress, inhibited neurogenesis, axon guidance, and promoted apoptosis. Supplementation with ascorbic acid could act as an antioxidant to prevent AgSC-mediated neurotoxicity.


Assuntos
Ácido Cítrico/química , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Prata , Apoptose/efeitos dos fármacos , Diferenciação Celular/genética , Linhagem Celular , Colesterol/biossíntese , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Células-Tronco Embrionárias Humanas/citologia , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/genética , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
2.
New Phytol ; 232(2): 835-852, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34289124

RESUMO

Despite a much higher proportion of intragenic heterochromatin-containing genes in crop genomes, the importance of intragenic heterochromatin in crop development remains unclear. Intragenic heterochromatin can be recognised by a protein complex, ASI1-AIPP1-EDM2 (AAE) complex, to regulate alternative polyadenylation. Here, we investigated the impact of rice ASI1 on global poly(A) site usage through poly(A) sequencing and ASI1-dependent regulation on rice development. We found that OsASI1 is essential for rice pollen development and flowering. OsASI1 dysfunction has an important impact on global poly(A) site usage, which is closely related to heterochromatin marks. Intriguingly, OsASI1 interacts with the intronic heterochromatin of OsXRNL, a nuclear XRN family exonuclease gene involved in the processing of an miRNA precursor, to promote the processing of full-length OsXRNL and regulate miRNA abundance. We found that OsASI1-mediated regulation of pollen development partially depends on OsXRNL. Finally, we characterised the rice AAE complex and its involvement in alternative polyadenylation and pollen development. Our findings help to elucidate an epigenetic mechanism governing miRNA abundance and rice development, and provide a valuable resource for studying the epigenetic mechanisms of many important processes in crops.


Assuntos
MicroRNAs , Oryza , Regulação da Expressão Gênica de Plantas , Heterocromatina/genética , MicroRNAs/genética , Oryza/genética , Pólen/genética , Poliadenilação
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