We can't find the internet
Attempting to reconnect
Something went wrong!
Hang in there while we get back on track
Prediction and validation of regulatory role of microRNAs in zebrafish (Danio rerio) responses to nanoparticle exposure with in silico and in vitro toxicological approaches
Summary
This thesis developed in silico and in vitro methods to predict how microRNAs regulate zebrafish responses to nanoparticle exposure, providing new tools for assessing nanoparticle toxicity. As nanoplastics are a type of nanoparticle, these methods have direct application to understanding how nanoplastics affect aquatic organisms at the molecular level.
The release of engineered nanoparticles as by-product of human activities in the environment can interfere with normal biology and health of the exposed organisms. MicroRNAs have been suggested as potential toxicology biomarkers, however the information about expression and role of microRNA in regulation of signaling pathways in organisms exposed to nanoparticles (NP) is limited. Summary of reported biological and pathological outcomes of NP induced toxicity in zebrafish was followed with in silico analysis of the genes potentially responsible for observed toxicological effects. After identifying relevant genes, we constructed six miRNA-mRNA regulatory networks involved in nanoparticle induced toxicological responses in zebrafish. Based on our prediction and selection criteria, we identified six miRNAs that overlapped in networks with high prediction scores, and were validated by previous mammalian and zebrafish microRNA profiling studies: dre-miR-124, -144, -148, -155, -19a, -223. As the next step, we validated the expression of these six miRNAs in THP-1 human monocytic cell line after the exposure to Polystyrene (PS NPs) and ARS labeled Titanium dioxide nanoparticles (TiO2-ARS NPs). Also, identification of miRNAs expression post exposure to PLGA nanoparticles and E. coli BioParticles was used to exclude potential activation and engagement of miRNAs through phagocytosis or pro-inflammatory specific responses. In our study, miR-155-5p showed the most promise as biomarker for PS NPs and TiO2-ARS NPs induced adverse effects. To determine potential for PS NPs and TiO2-ARS NPs for genotoxicity, time and dose dependent DNA damage profile induced by PS NPs or TiO2-ARS NPs was established by comet assay. Results indicated the severe DNA damage was triggered by both PS NPs and TiO2-ARS NPs. However, we observed that the expression of DNA damage repairing genes was elevated post TiO2-ARS NPs but not post PS NPs exposure, questioning the utility of the comet assay as universal assessment tool for genotoxicity induced by nanoparticles in general. It was observed that after PS NPs exposure the successful transfection of miR-155-5p mimic induced the expression of ATM, TAOK1, TRIP13, and APAF-1 while the expression of ERCC1 was attenuated. The ATM, APAF-1 and RAD51 were strongly activated post TiO2-ARS NPs stimulation in mimic-transfected cells. These observations suggest there is significant involvement of miR-155-5p in PS NPs and TiO2-ARS NPs induced adverse effects.
Sign in to start a discussion.
More Papers Like This
In vivo biotoxicological assessment of nanoplastics and microplastics predicted using the zebrafish model
This review summarises zebrafish studies on the toxicity of nanoplastics and microplastics, covering developmental, reproductive, neurological, and organ-level effects. It discusses how findings in this widely used model organism may predict human health outcomes and calls for standardised exposure protocols.
Advantages of the zebrafish (Danio rerio) model in solving contemporary problems of neurotoxicity, teratotoxicity and genotoxicity of xenobiotics
This paper is not about microplastics per se; it is a Polish-language review of the zebrafish (Danio rerio) model in toxicology, covering its use for assessing neurotoxicity, teratotoxicity, and genotoxicity of xenobiotics including nanoparticles and microplastics, with discussion of the micronucleus and comet assays used to detect genetic damage.
From particle size to brain function: a zebrafish-based review of micro/nanoplastic-induced neurobehavioral toxicity and mechanistic pathways
This review uses zebrafish as a model to examine how micro- and nanoplastics cause neurobehavioral toxicity, linking particle size to brain function disruption. Researchers summarize evidence that these plastic particles impair fish behavior and cause molecular-level damage in the nervous system. The findings highlight the growing concern that micro- and nanoplastics are emerging neurotoxicants in aquatic environments.
Nanoplastics impact the zebrafish (Danio rerio) transcriptome: Associated developmental and neurobehavioral consequences
Researchers exposed developing zebrafish larvae to polystyrene nanoplastics of two sizes and found dose-dependent accumulation in tissues along with swimming hyperactivity, despite no effects on mortality or hatching. Transcriptomic analysis revealed changes in gene expression associated with neurodegeneration and motor dysfunction at both high and low concentrations. The study suggests that nanoplastic exposure during early development can alter brain function and behavior in ways that may reduce organismal fitness.
Computational genomics of zebrafish under micro- and Nanoplastic stress: identification of pathways and hub genes
This in silico review used protein-protein interaction networks and computational toxicogenomics to identify hub genes—including casp3a, tp53, and nfe2l2a—as central regulators of zebrafish responses to micro- and nanoplastic stress, providing targets for mechanistic and biomarker research.