Antioxidants
·
2025
·Vol. 14
·期 6
·641
·
IF 6.6
Zhonglian Ma,Liang Ma,Yuhao Zhang
Acrylamide (ACR), utilized as a precursor for producing polyacrylamide for water purification, has demonstrated neurotoxic properties. However, the mechanisms underlying its neurotoxicity remain inadequately understood. In this investigation,Caenorhabditis eleganswere exposed to ACR at concentrations ranging from 250 to 1000 μg/mL and then their locomotor behavior, neuronal development, neurotransmitter concentrations, and gene expression profiles were assessed. Exposure to 250–1000 μg/mL ACR resulted in observable behaviors such as head swiveling and body bending, accompanied by a significant reduction in body size. Furthermore, ACR exposure caused damage to serotonergic, cholinergic, dopaminergic, and glutamatergic neuronal structures. In this context, elevated levels of serotonin, dopamine, acetylcholine, and glutamate were detected, along with notable upregulation of the expression of genes associated with neurotransmitters, includingtph-1,cat-4,mod-1,mod-5,cat-1,ser-1,dat-1,dop-1,dop-3,unc-17,cho-1,eat-4, andglr-2. Moreover, ACR exposure elevated reactive oxygen species (ROS), O2, and H2O2levels while concurrently depleting glutathione (GSH), thereby compromising the antioxidant defense system. This led to a significant upsurge in the expression of genes involved in the nematode ACR detoxification pathway, specificallydaf-16,skn-1,mlt-1,sod-3,gst-4,gcs-1,hsf-1, andhsp-16.2. Additionally, Spearman correlation analysis revealed a significant inverse relationship between certain neurotransmitter and antioxidant genes and locomotor activities, highlighting the role of these genes in mediating ACR-induced neurotoxicity inC. elegans. Collectively, this research enhances the understanding of the mechanisms related to ACR neurotoxicity.
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GERONTOLOGY
·
2024
·
IF 3.1
Liang Yu,Zhou Yiming,Zhou Can,Cai Xinqi,Liu Li,Wei Fang,Li Guolin
Introduction: While several antidepressants have been identified as potential geroprotectors, the effect and mechanism of sertraline on healthspan remain to be elucidated. Here, we explored the role of sertraline in the lifespan and healthspan of Caenorhabditis elegans. Methods: The optimal effect concentration of sertraline was first screened in wild-type N2 worms under heat stress conditions. Then, we examined the effects of sertraline on lifespan, reproduction, lipofuscin accumulation, mobility, and stress resistance. Finally, the expression of serotonin signaling and aging-related genes was investigated to explore the underlying mechanism, and the lifespan assays were performed in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants. Results: Sertraline extended the lifespan in C. elegans with concomitant extension of healthspan as indicated by increasing mobility and reducing fertility and lipofuscin accumulation, as well as enhanced resistance to different abiotic stresses. Mechanistically, ser-7 orchestrated sertraline-induced longevity via the regulation of insulin and AMPK pathways, and sertraline-induced lifespan extension in nematodes was abolished in ser-7 RNAi strain, daf-2, daf-16, and aak-2 mutants. Conclusion: Sertraline promotes health and longevity in C. elegans through ser-7-insulin/AMPK pathways
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TOXICOLOGY
·
2022
·
IF 4.571
Jielin Tang,Jiayi Li,Qinyu Zhou,Guzailinuer Kuerban,Jinyan Qin,Hongdan Zhang,Rongli Sun,Lihong Yin,Yuepu Pu,Juan Zhang
As a new type of flame retardant , Organic Phosphate Flame Retardant has been widely used worldwide. The purpose of our research is to determine the neurotoxicity of Tris (1,3-dichloroisopropyl) phosphate (TDCPP) to Caenorhabditis elegans and its mechanism. L1 larvae wild-type C. elegans were exposed to different concentrations of TDCPP, and the effects on motor behavior (head thrashes, body bends, pumping times, chemotaxis index), ROS levels, and p38MAPK signaling pathway-related gene expression levels were measured. Three transgenic nematode strains, BZ555, DA1240, and EG1285, were also used to study the effects of TDCPP on nematode dopamine neurons, glutamate neurons, and GABA neurons. The results showed that TDCPP can inhibit the head thrashes and body bends of the nematode, reduce dopamine production, increase the level of ROS in the body, and affect the expression of genes related to the p38MAPK signaling pathway. We next employed ROS production and motor behavior as toxicity assessment endpoints to determine the involvement of p38 MAPK signaling in the regulation of response to TDCPP. The results showed that the nematodes with low expression of pmk-1 were less sensitive to the TDCPP. It was suggested that TDCPP had neurotoxicity and regulated neurotoxicity to C. elegans by activating the p38-MAPK signaling pathway. The research in this article provides important information for revealing the environmental health risks of organophosphorus flame retardants and their toxic mechanism of action.
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JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
·
2023
·Vol. 79
·期 1
·
IF 5.1
Zhou Can,Zhou Yiming,Liang Yu,Chen Lijuan,Liu Li,Wei Fang,Li Guolin
Although several antidepressants have been identified as potential geroprotectors, the effect and mechanism of fluoxetine, a representative selective serotonin reuptake inhibitor, on longevity have not been fully elucidated. Here, we found that fluoxetine promoted longevity in Caenorhabditis elegans with a concomitant extension of a healthy life span as indicated by increasing mobility, reducing fertility and lipofuscin accumulation, and enhanced resistance to different abiotic stresses. Fluoxetine increased the level of reactive oxygen species (ROS), and antioxidant N-acetylcysteine abolished ROS elevation and the pro-longevity effect of fluoxetine. Additionally, fluoxetine extended life span through the daf-2-sod-3 pathway in daf-16-dependent and -independent manners, and fluoxetine-induced life-span extension was abolished in C. elegans sod-3, daf-2, and daf-16 mutants. In conclusion, these findings suggest that fluoxetine can promote health and longevity in C. elegans via the interaction of ROS and insulin signaling.
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eLife
·
2025
·
IF 0
Yi Li,Long Gong,Jing Wu,Wesley Hung,Mei Zhen,Shangbang Gao
Resistance to anthelmintics, particularly the macrocyclic lactone ivermectin (IVM), presents a substantial global challenge for parasite control. We found that the functional loss of an evolutionarily conserved E3 ubiquitin ligase, UBR-1, leads to IVM resistance in Caenorhabditis elegans. Multiple IVM-inhibiting activities, including viability, body size, pharyngeal pumping, and locomotion, were significantly ameliorated in various ubr-1 mutants. Interestingly, exogenous application of glutamate induces IVM resistance in wild-type animals. The sensitivity of all IVM-affected phenotypes of ubr-1 is restored by eliminating proteins associated with glutamate metabolism or signaling: GOT-1, a transaminase that converts aspartate to glutamate, and EAT-4, a vesicular glutamate transporter. We demonstrated that IVM-targeted GluCls (glutamate-gated chloride channels) are downregulated and that the IVM-mediated inhibition of serotonin-activated pharynx Ca2+ activity is diminished in ubr-1. Additionally, enhancing glutamate uptake in ubr-1 mutants through ceftriaxone completely restored their IVM sensitivity. Therefore, UBR-1 deficiency-mediated aberrant glutamate signaling leads to ivermectin resistance in C. elegans.
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BIOGERONTOLOGY
·
2023
·Vol. 24
·期 4
·581-592
·
IF 4.5
Ma Jing,Wang Yi-ting,Chen Ling-hui,Yang Bang-ya,Jiang Yong-zhu,Wang Lan-xi,Chen Zhi-qi,Ma Guan-rong,Fang Liao-qiong,Wang Zhi-biao
There is growing evidence that extracellular vesicles (EVs) play a functional role in tissue repair and anti-aging by transferring the contents of donor cells to recipient cells. We hypothesized that Dauer ( C. elegans ), known as “ageless” nematodes, can also secrete extracellular vesicles and influence the lifespan of C. elegans . Here, we isolated EVs of dauer larvae (dauer EVs). Dauer EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA), and Western blot analysis. Wild-type C. elegans were fed in the presence or absence of dauer EVs and tested for a range of phenotypes, including longevity, mobility and reproductive capacity. Results showed that dauer EVs increased the average lifespan of nematodes by 15.74%, improved mobility, slowed age-related pigmentation as well as body length, and reduced the accumulation of reactive oxygen species and lipids, while not impairing nematode reproductive capacity. These findings suggest that dauer EVs can extend the lifespan of C. elegans as well as the healthy lifespan by reducing ROS accumulation, with potential anti-aging capacity.
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Biomolecules
·
2023
·Vol. 13
·期 1
·102
·
IF 5.5
Jing Yuan,Fei Lin,Zhiyong Wu,Zhilin Jiang,Ting Wang,Sitong Huo,Weinan Lai,Li Li,Chao Zhang
Radioactive substances have been used in various aspects in daily life. However, high-energy radiation could cause environmental problems, which would damage the human body. Circular RNA (CircRNA) has great potential in the minimization of ionizing radiation damage. To find a potential diagnostic and therapeutic target for reducing the damage of ionizing radiation, we selected circRNA cleavage and polyadenylation specificity factor subunit 1 (circ-CPSF1) based on its up-regulated expression after X-ray radiation and explored its effect on response to ionizing radiation usingCaenorhabditis elegans(C. elegans). Circ-CPSF1 was screened out and its up-regulated expression was verified. The measurement of lifespan and germ cell apoptosis showed that circ-CPSF1 RNAi treatment extended lifespan and reduced apoptotic germ cells. ROS levels were significantly reduced after the interference of circ-CPSF1 inC. eleganswith radiation. Mitochondrial membrane potential assay showed that the suppression of circ-CPSF1 could alleviate mitochondrial damage after radiation. Relative genes expression showed the involvement of circ-CPSF1 in radiation mediated DNA damage response pathways and apoptosis pathways. In conclusion, circ-CPSF1 exerts deleterious effects on lifespan, eggs production and germ cell apoptosis ofC. elegansthrough oxidative stress, the DNA damage response (DDR) pathway, and the core apoptotic pathway after ionizing radiation, indicating the potential of circ-CPSF1 to be an important therapeutic target of radiation damage.Keywords:radiation;circ-CPSF1;DNA damage response (DDR);apoptosis
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Journal of Ginseng Research
·
2022
·
IF 5.735
Hao Shi,Jiamin Zhao,Yiwen Li,Junjie Li,Yunjia Li,Jia Zhang,Zhantu Qiu,Chaofeng Wu,Mengchen Qin,Chang Liu,Zhiyun Zeng,Chao Zhang,Lei Gao
Background Obesity is a risk factor for aging and many diseases, and the disorder of lipid metabolism makes it prominent. This study aims to investigate the effect of ginsenoside Rg1 on aging, lipid metabolism and stress resistance Methods Rg1 was administered to Caenorhabditis elegans ( C. elegans ) cultured in NGM or GNGM. The lifespan, locomotory activity, lipid accumulation, cold and heat stress resistance and related mRNA expression of the worms were examined. Gene knockout mutants were used to clarify the effect on lipid metabolism of Rg1. GFP-binding mutants were used to observe the changes in protein expression Results We reported that Rg1 reduced lipid accumulation and improved stress resistance in C. elegans . Rg1 significantly reduced the expression of fatty acid synthesis-related genes and lipid metabolism-related genes in C. elegans . However, Rg1 did not affect the fat storage in fat-5/fat-6 double mutant or nhr-49 mutant. Combined with network pharmacology, we clarified the possible pathways and targets of Rg1 in lipid metabolism. In addition, Rg1-treated C. elegans showed a higher expression of anti-oxidative genes and heat shock proteins, which might contribute to stress resistance Conclusion Rg1 reduced fat accumulation by regulating lipid metabolism via nhr-49 and enhanced stress resistance by its antioxidant effect in C. elegans .
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SCIENCE OF THE TOTAL ENVIRONMENT
·
2021
·
IF 7.963
Qiang Chu,Shuang Zhang,Xin Yu,Yaxuan Wang,Mingkui Zhang,Xiaodong Zheng
Current studies simply focus on the toxicity of nano-plastics, while the correlation between their toxicity and bio-distribution, as well as intestinal microorganisms is still blank. Therefore, we systematically evaluated the toxicity based on the accumulation characteristics of nano-plastics in C. elegans . Meanwhile, for the first time, human fecal microbiota was transplanted into the gut of C. elegans and found that nano-plastics can through the intestinal barrier to the whole body after oral intake and can't be drastically excreted until die, thus causing toxic effects; while human fecal microbiota transplantation can significantly improve the living state via activating PMK-1/SKN-1 pathway to promote the production of intracellular glutathione, and exogenous glutathione addition can also markedly protect nematodes against nano-plastics induced toxicity. Our results not only provide a fully understand between the accumulation characteristic and health risk of nano-plastics, but also take C. elegans and intestinal flora into the field of toxicity evolution of nanomaterials.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2016
·
IF 3.055
Ju Zhang,Ruona Shi,Haifeng Li,Yanxia Xiang,Lingyun Xiao,Minghua Hu,Fangli Ma,Chung Wah Ma,Zebo Huang
Ethnopharmacological relevance Dictyophora indusiata is a medicinal mushroom traditionally used in China for a variety of conditions, including inflammatory and neural diseases. D. indusiata polysaccharides (DiPS) are shown to have in vitro antioxidant activity but in vivo evidence is lacking. This study aimes to explore the antioxidant capacity and related neuroptotective activities of DiPS using wild-type and neurodegenerative Caenorhabditis elegans models. Materials and methods The antioxidant capacities of DiPS were first determined using paraquat survival and Pgst-4 ::GFP expression assays in wild-type and transgenic C. elegans models, respectively, and then further investigated by determining reactive oxygen species (ROS) level, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity as well as functional parameters of mitochondria. The activation of stress response transcription factors and neuroptotective activities were examined using nuclear localization and chemosensory behavioral assays in transgenic nematodes, respectively. Results DiPS was shown not only to increase survival rate and reduce stress level under paraquat-induced oxidative conditions but also to decrease ROS and MDA levels and increase SOD activity in C. elegans models. Moreover, DiPS was also able to restore the functional parameters of mitochondria, including membrane potential and ATP content, in paraquat-stressed nematodes. In addition, nuclear translocation assays demonstrate that the stress response transcription factor DAF-16/FOXO was involved in the antioxidant activity of the polysaccharide. Further experiments reveal that DiPS was capable of reducing ROS levels and alleviating chemosensory behavior dysfunction in transgenic nematode models of neurodegenerative diseases mediated by polyglutamine and amyloid-β protein. Conclusions These findings demonstrate the antioxidant and neuroprotective activities of the D. indusiata polysaccharide DiPS in wild-type and neurodegenerative C. elegans models, and thus provide an important pharmacological basis for the therapeutic potential of D. indusiata in neurodegeneration .
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ENVIRONMENTAL POLLUTION
·
2020
·
IF 6.793
Shuang Zhang,Qiang Chu,Zhang Zhang,Yingfei Xu,Xiali Mao,Mingkui Zhang
The surface modifications of nanoparticles (NPs), are well-recognized parameters that affect the toxicity, while there has no study on toxicity of Al 2 O 3 NPs with different surface modification. Therefore, for the first time, this study pays attention to evaluating the toxicity and potential mechanism of pristine Al 2 O 3 NPs (p-Al 2 O 3 ), hydrophilic (w-Al 2 O 3 ) and lipophilic (o-Al 2 O 3 ) modifications of Al 2 O 3 NPs both in vitro and in vivo . Applied concentrations of 10, 20, 40, 80,100 and 200 μg/mL for 24 h exposure on Caenorhabditis elegans ( C. elegans ), while 100 μg/mL of Al 2 O 3 NPs significantly decreased the survival rate. Using multiple toxicological endpoints, we found that o-Al 2 O 3 NPs (100 μg/mL) could induce more severe toxicity than p-Al 2 O 3 and w-Al 2 O 3 NPs. After uptake by C. elegans , o-Al 2 O 3 NPs increased the intestinal permeability, easily swallow and further destroy the intestinal membrane cells. Besides, cytotoxicity evaluation revealed that o-Al 2 O 3 NPs (100 μg/mL) are more toxic than p-Al 2 O 3 and w-Al 2 O 3 . Once inside the cell, o-Al 2 O 3 NPs could attack mitochondria and induce the over-production of reactive oxygen species (ROS), which destroy the intracellular redox balance and lead to apoptosis. Furthermore, the transcriptome sequencing and RT-qPCR data also demonstrated that the toxicity of o-Al 2 O 3 NPs is highly related to the damage of cell membrane and the imbalance of intracellular redox. Generally, our study has offered a comprehensive sight to the adverse effects of different surface modifications of Al 2 O 3 NPs on environmental organisms and the possible underlying mechanisms.
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BIOGERONTOLOGY
·
2022
·Vol. 23
·期 4
·485-497
·
IF 4.284
Wang Lixin,Qiao Ping,Ouyang Zhuoer,Li Danyang,Zheng Jingtong,Wang Guoqiang,Wang Fang
Ginseng volatile oil (GVO) is one of the main components of ginseng and has antibacterial and anti-inflammatory properties. In this study, gas chromatography–mass spectrometry (GC–MS) was applied to characterize GVO chemical composition, and 73 volatile components were detected from GVO. Caenorhabditis elegans was used as animal model to further elucidate the antioxidant and anti-aging effects of GVO in vivo. The results suggested that GVO significantly prolonged the lifespan of C. elegans and promoted its health without damaging its reproductive capacity. In addition, GVO increased the antioxidant capacity and survival rate of nematodes after heat shock. Transcriptional sequencing showed that autophagy-related genes atg-4.2 , atg-7 , lgg-2 , and cyd-1 were up-regulated, and superoxide dismutase 1 ( sod-1 ) expression was increased after GVO pretreatment. Considering the role of autophagy and antioxidant in aging, the expression of autophagy substrate P62 protein in BC12921 strain was analyzed and found to decrease by more than 50.00% after treatment with GVO. In addition, the lifespan of SOD-1 mutant nematodes was not significantly different from that of the control group. SOD activity and autophagy were activated, which is a clear expression of hormesis. All these results suggest that GVO prolongs the lifespan and healthspan of C. elegans , and its biological functions may be related to hormesis.
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