We can't find the internet
Attempting to reconnect
Something went wrong!
Hang in there while we get back on track
Nanoplastic-induced NAT10/ac4C axis drives both oxidative stress and chemoresistance
AI summary Read the abstract
Researchers discovered that polystyrene nanoplastics trigger an epitranscriptomic stress response in cells by activating the enzyme NAT10, which hypermodifies transfer RNA with N4-acetylcytidine (ac4C) marks — and found this same pathway also reduces the effectiveness of the cancer drug sorafenib by nearly fourfold, establishing a direct link between nanoplastic exposure and impaired chemotherapy response.
The exact molecular mechanisms of nanoplastics toxicity remain poorly understood. This study provides the first evidence that exposure to polystyrene nanoparticles (PS-NPs) induces a significant epitranscriptomic reprogramming, detecting 38 different tRNA mononucleotides and 49 oligonucleotides through a derivatization-LC-MS/MS approach. PS-NPs induced potent oxidative stress, marked by a 3.1-fold increase in reactive oxygen species (ROS) and a 2.6-fold increase in the RNA damage marker 8-oxo-GMP. Furthermore, this stress upregulated the acetyltransferase NAT10, leading to N4-acetylcytidine (ac4C) hypermodification that occurred specifically within the D-loop of tRNA under nanoplastics stress. Interestingly, NAT10/ac4C axis activation could also decrease the sensitivity to the chemotherapeutic agent sorafenib, increasing its IC from 6.9 μM to 25.7 μM. Crucially, this chemoresistance was reversed by both pharmacological inhibition (with Remodelin) and genetic knockdown (with siRNA) of NAT10, which subsequently ameliorated oxidative stress and re-sensitized the cells to sorafenib, confirming the pathway's causal role in modulating cellular response to nanoplastic exposure. Our findings establish the upregulation of the NAT10/ac4C axis as a targeted, adaptive response to nanoplastics-induced stress, revealing a direct mechanistic link between an environmental pollutant and impaired chemotherapeutic efficacy. This identifies the NAT10/ac4C axis as both a key mediator of nanoplastics toxicity and a promising therapeutic target to restore cellular health.
More Papers Like This
Environmental Concentrations of Polystyrene Nanoplastics Induce Low‐Dose Tamoxifen Toxicity Through Oxidative Stress in Caenorhabditis elegans
AI summary Read the abstract
Researchers used the model organism C. elegans to investigate how environmental concentrations of polystyrene nanoplastics interact with the cancer drug tamoxifen. Combined exposure significantly impaired locomotion, reproduction, and growth while inducing oxidative stress through the DAF-2/DAF-16 insulin signaling pathway. The study suggests that long-term exposure to environmental levels of nanoplastics could enhance the side effects of pharmaceutical drugs in living organisms.
Polystyrene Nanoplastics Induce Lipid Metabolism Disorder by Activating the PERK-ATF4 Signaling Pathway in Mice
AI summary Read the abstract
Mice exposed to polystyrene nanoplastics developed abnormal fat buildup in their livers through a specific stress pathway in cells called the endoplasmic reticulum. The nanoplastics activated a signaling chain (PERK-ATF4) that ramped up fat-producing genes, leading to excess fat droplets in liver tissue -- a finding that helps explain how nanoplastic exposure could contribute to liver disease and metabolic problems.
Transgenerational response of germline histone acetyltransferases and deacetylases to nanoplastics at predicted environmental doses in Caenorhabditis elegans
AI summary Read the abstract
Researchers showed that polystyrene nanoplastics at environmentally predicted doses suppress germline histone acetyltransferases and deacetylases in C. elegans, and that silencing these chromatin-regulating enzymes worsened toxicity across multiple generations by dysregulating signaling ligands — identifying histone deacetylase inhibition as the molecular initiating event in an epigenetic adverse outcome pathway.
Microplastics impair wound healing via NAT10-mediated epigenetic dysregulation of FASN-PI3K/AKT signaling
AI summary Read the abstract
Researchers found that microplastic exposure significantly delayed wound healing in both diabetic and non-diabetic mice, with transcriptomic analysis revealing that microplastics suppress the wound healing pathway through NAT10-mediated epigenetic regulation of FASN-PI3K/AKT signaling, with stronger effects in diabetic animals.
Nanoplastics increase in vitro oestrogenic activity of neurotherapeutic drugs
AI summary Read the abstract
Researchers found that polystyrene nanoplastics significantly enhance the estrogenic activity of neurotherapeutic drugs in vitro, suggesting that nanoplastic contamination of drinking water and food could increase hormonal exposures from pharmaceutical residues.
Research digests by email
When a large batch of papers lands in the Atlas, we read through it and send a short write-up of what stood out.