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النتائج 1 - 10 من 19
Reactive oxygen species-evoked endoplasmic reticulum stress mediates 1-nitropyrene-induced epithelial-mesenchymal transition and pulmonary fibrosis
2021
Fu, Lin | Zhao, Hui | Xiang, Ying | Xiang, Hui-Xian | Hu, Biao | Tan, Zhu-Xia | Lu, Xue | Gao, Lan | Wang, Bo | Wang, Hua | Zhang, Cheng | Xu, De-Xiang
1-Nitropyrene (1-NP) is one component of atmospheric fine particles. Previous report revealed that acute 1-NP exposure induced respiratory inflammation. This study aimed to investigate whether chronic 1-NP exposure induces pulmonary fibrosis. Male C57BL6/J mice were intratracheally instilled to 1-NP (20 μg/mouse/week) for 6 weeks. Diffuse interstitial inflammation, a-smooth muscle actin (a-SMA)-positive cells, a marker of epithelial-mesenchymal transition (EMT), and an extensive collagen deposition, measured by Masson staining, were observed in 1-NP-exposed mouse lungs. Pulmonary function showed that lung dynamic compliance (Cydn-min) was reduced in 1-NP-exposed mice. Conversely, inspiratory resistance (Ri) and expiratory resistance (Re) were elevated in 1-NP-exposed mice. Mechanistically, cell migration and invasion were accelerated in 1-NP-exposed pulmonary epithelial cells. In addition, E-cadherin, an epithelial marker, was downregulated, and vimentin, a-SMA and N-cadherin, three mesenchymal markers, were upregulated in 1-NP-exposed pulmonary epithelial cells. Although TGF-β wasn’t altered, phosphorylated Smad2/3 were enhanced in 1-NP-exposed pulmonary epithelial cells. Moreover, reactive oxygen species (ROS) were increased and endoplasmic reticulum (ER) stress was activated in 1-NP-exposed pulmonary epithelial cells. N-Acetylcysteine (NAC), an antioxidant, attenuated 1-NP-evoked excess ROS, ER stress and EMT in pulmonary epithelial cells. Similarly, pretreatment with NAC alleviated 1-NP-caused pulmonary EMT and lung fibrosis in mice. These results demonstrate that ROS-evoked ER stress contributes, at least partially, to 1-NP-induced EMT and pulmonary fibrosis.
اظهر المزيد [+] اقل [-]Polystyrene microplastics disrupt the blood-testis barrier integrity through ROS-Mediated imbalance of mTORC1 and mTORC2
2021
Wei, Yuexin | Zhou, Yu | Long, Chunlan | Wu, Huan | Hong, Yifan | Fu, Yan | Wang, Junke | Wu, Yuhao | Shen, Lianju | Wei, Guanghui
It has been found that polystyrene microplastics (PS-MPs) exposure leads to decreased sperm quality and quantity, and we aim to explore the underlying mechanisms. Therefore, we gave 20 mg/kg body weight (bw) and 40 mg/kg bw 4 μm and 10 μm PS-MPs to male Balb/c mice by gavage. RNA sequencing of testes was performed. After PS-MPs exposure, blood-testis barrier (BTB) integrity was impaired. Since cytoskeleton was closely related to BTB integrity maintenance, and cytoskeleton disorganization could be induced by PS-MPs exposure in the testis, which resulted in the truncation of actin filaments and disruption of BTB integrity. Such processes were attributed to the differential expression of Arp3 and Eps8 (two of the most important actin-binding proteins). According to the transcriptome sequencing results, we examined the oxidative stress level in the testes and Sertoli cells. We found that PS-MPs exposure induced increased reactive oxygen species (ROS) level, which destroyed the balance between mTORC1 and mTORC2 (the mTORC1 activity was increased, while the mTORC2 activity was decreased). In conclusion, PS-MPs induced the imbalance of mTORC1 and mTORC2 via the ROS burst, and altered the expression profile of actin-binding proteins, resulting in F-actin disorganization and reduced expression of junctional proteins in the BTB. Eventually PS-MPs led to BTB integrity disruption and spermatogenesis dysfunction.
اظهر المزيد [+] اقل [-]Molecular mechanisms underlying the calcium-mediated uptake of hematite nanoparticles by the ciliate Tetrahymena thermophila
2021
Wu, Chao | Guo, Wen-Bo | Liu, Yue-Yue | Yang, Liuyan | Miao, Ai-Jun
In aquatic ecosystems, the calcium (Ca) concentration varies greatly. It is well known that Ca affects the aggregation of nanoparticles (NPs) and thus their bioaccumulation. Nevertheless, Ca also plays critical roles in various biological processes, whose effects on NP accumulation in aquatic organisms remain unclear. In this study, the effects of Ca on the uptake of polyacrylate-coated hematite NPs (HemNPs) by the aquatic ciliate Tetrahymena thermophila were investigated. At all of the tested Ca concentrations, HemNPs were well dispersed in the experimental medium, excluding the possibility of Ca to influence HemNP bioaccumulation by aggregating the NPs. Instead, Ca was shown to induce the clathrin-mediated endocytosis and phagocytosis of HemNPs. Manipulation of the Ca speciation in the experimental medium as well as the influx and intracellular availability of Ca in T. thermophila indicated that HemNP uptake was regulated by the intracellular Ca level. The results of the proteomics analyses further showed that the binding of intracellular Ca to calmodulin altered the activity of proteins involved in clathrin-mediated endocytosis (calcineurin and dynamin) and phagocytosis (actin). Overall, the biologically inductive effects of Ca on NP accumulation in aquatic organisms should be considered when evaluating the environmental risks of NPs.
اظهر المزيد [+] اقل [-]Tissue distribution of polystyrene nanoplastics in mice and their entry, transport, and cytotoxicity to GES-1 cells
2021
Ding, Yunfei | Zhang, Ruiqing | Li, Boqing | Du, Yunqiu | Li, Jing | Tong, Xiaohan | Wu, Yulong | Ji, Xiaofei | Zhang, Ying
With the widespread use of plastics and nanotechnology products, nanoplastics (NPs) have become a potential threat to human health. It is of great practical significance to study and evaluate the distribution of NPs in mice as mammal models and their entry, transport, and cytotoxicity in human cell lines. In this study, we detected the tissue distribution of fluorescent polystyrene nanoplastics (PS-NPs) in mice and assessed their endocytosis, transport pathways, and cytotoxic effects in GES-1 cells. We found that PS-NPs were clearly visible in gastric, intestine, and liver tissues of mice and in GES-1 cells treated with PS-NPs. Entry of PS-NPs into GES-1 cells decreased with the inhibition of caveolae-mediated endocytosis (nystatin), clathrin-mediated endocytosis (chlorpromazine HCl), micropinocytosis (ethyl-isopropyl amiloride), RhoA (CCG-1423), and F-actin polymerization (lantrunculin A). Rac1 inhibitors (NSC 23766) had no significant effect on PS-NPs entering GES-1 cells. F-actin levels significantly decreased in CCG-1423-pretreated GES-1 cells exposed to PS-NPs. GES-1 cell ultrastructural features indicated that internalized PS-NPs can be encapsulated in vesicles, autophagosomes, lysosomes, and lysosomal residues. RhoA, F-actin, RAB7, and LAMP1 levels in PS-NPs-treated GES-1 cells were remarkably up-regulated and the Rab5 level was significantly down-regulated compared to levels in untreated cells. PS-NPs treatment decreased cell proliferation rates and increased cell apoptosis. The formation of autophagosomes and autolysosomes and levels of LC3II increased with the length of PS-NPs treatment. The results indicated that cells regulated endocytosis in response to PS-NPs through the RhoA/F-actin signaling pathway and internalized PS-NPs in the cytoplasm, autophagosomes, or lysosomes produced cytotoxicity. These results illustrate the potential threat of NPs pollution to human health.
اظهر المزيد [+] اقل [-]In ovo very early-in-life exposure to diesel exhaust induced cardiopulmonary toxicity in a hatchling chick model
2020
Jiang, Qixiao | Xu, Xiaohui | Zhang, Chao | Luo, Jing | Lv, Na | Shi, Limei | Ji, Andong | Gao, Mengyu | Chen, Feilong | Cui, Lianhua | Zheng, Yuxin
Diesel exhaust (DE) had been associated with cardiopulmonary toxicity and developmental toxicity. However, neonatal very early-in-life exposure had not been extensively studied previously. To investigate the potential effects of neonatal very early-in-life exposure to DE, a brand-new chicken embryo in ovo exposure model had been established, with which the cardiopulmonary effects of DE exposure via air cell infusion at embryonic day 18/19 (ED18/19) were assessed in hatchling chicks post-hatch 0-, 1-, or 2-weeks. Heart rates were assessed with electrocardiography. Cardiac and pulmonary morphologies were investigated with histopathological methods. Cardiopulmonary effects were explored with immunohistochemistry for alpha smooth muscle actin (alpha-SMA). In further investigations, the expression levels of phosphorylated AhR, serum levels of TGF-β1, phosphorylated SMAD2/3 and phosphorylated p38MAPK were assessed in the lung tissues. Significantly elevated heart rates, increased right ventricular wall thickness and cardiac collagen deposition were observed in the hearts of exposed hatchling chicks. Significantly increased collagen deposition as well as increased vascular alpha-SMA layer thickness/decreased cavity area were observed in exposed animal lungs. These effects persisted up to two weeks post-hatch. Mechanistic studies revealed elevated phosphorylated AhR expression levels in 0-week and 1-week chicken lungs, while phosphorylated SMAD2/3 levels significantly increased in 0-week chicken lungs but decreased in 2-week chicken lungs following DE exposure. Phosphorylation of p38MAPK did not remarkably increase until 2-week post-hatch. In summary, the novel chicken neonatal very early-in-life exposure model effectively exposed the chicken embryos during the neonatal initial breathing, resulting in cardiopulmonary toxicity, which is associated with AHR, TGF-β1 and MAPK signaling.
اظهر المزيد [+] اقل [-]Glutathione alleviates the cadmium exposure-caused porcine oocyte meiotic defects via eliminating the excessive ROS
2019
Zhou, Changyin | Zhang, Xue | Chen, Yixuan | Liu, Xiangping | Sun, Yuxin | Xiong, Bo
Heavy metal cadmium (Cd) is a widespread environmental contaminant with a potential toxicity that might adversely influence the health of experimental animals and humans. It has been known that Cd might accumulate in vertebrates for many years and thus leads to the hepatic and renal toxicity. Additionally, Cd concentration in the ovary increases with age and is highly related to the reproductive hazard. However, the underlying mechanisms regarding how Cd affects the female reproductive system especially the oocyte quality have not yet fully defined. Here, we reported that Cd exposure led to the defective nuclear maturation of oocytes via the impairment of cytoskeleton assembly, displaying the aberrant spindle organization, chromosome alignment and actin polymerization. In the meantime, Cd exposure caused the impaired cytoplasmic maturation by showing the disrupted dynamics of mitochondrial integrity and cortical granules, and thereby resulting in the compromised sperm binding ability and fertilization capacity of oocytes. More importantly, we found that glutathione (GSH) supplementation was able to recover the meiotic failure induced by Cd exposure through suppressing the excessive ROS level, DNA damage accumulation and apoptotic incidence. Taken together, our findings demonstrate that Cd exposure has the adverse effects on the oocyte meiotic maturation as well as subsequent fertilization, and provide a potential effective strategy to improve the quality of Cd-exposed oocytes.
اظهر المزيد [+] اقل [-]2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced suppression of immunity in THP-1-derived macrophages and the possible mechanisms
2021
Li, Xinyan | Li, Na | Han, Yingnan | Rao, Kaifeng | Ji, Xiaoya | Ma, Mei
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known immunotoxic environmental pollutant. However, most immunotoxicology studies of TCDD were based on the animal models and the inner mechanisms have just focused on a few genes/proteins. In this study, the immune functions of THP-1-derived macrophages was measured with in-vitro bioassays after 24-h exposure of TCDD including environmentally relevant concentrations. RNA-seq and Weighted Gene Co-expression Network Analysis were used to characterize the immunotoxicity molecular mechanisms. Our study is the first report on the TCDD-induced effects of cell adhesion, morphology, and multiple cytokines/chemokines production on THP-1 macrophages. After TCDD treatment, we observed an inhibited cell adherence, probably attributed to the suppressed mRNA levels of adhesion molecules ICAM-1, VCAM-1 and CD11b, and a decrease in cell pseudopodia and expression of F-actin. The inflammatory cytokines TNF-α, IL-10 and other 8 cytokines/chemokines regulating granulocytes/T cells and angiogenesis were disrupted by TCDD. Alternative splicing event was found to be a sensitive target for TCDD. Using WGCNA, we identified 10 hub genes (TNF, SRC, FGF2, PTGS2, CDH2, GNG11, BDNF, WNT5A, CXCR5 and RUNX2) highly relevant to these observed phenotypes, suggesting AhR less important in the effects TCDD have on THP-1 macrophages than in other cells. Our findings broaden the understanding of TCDD immunotoxicity on macrophages and provide new potential targets for clarifying the molecular mechanisms.
اظهر المزيد [+] اقل [-]Biochemical profile and gene expression of Clarias gariepinus as a signature of heavy metal stress
2020
Swaleh, Sadiya Binte | Banday, Umarah Zahoor | Asadi, Moneeb-Al | Usmani, Nazura
Heavy metals have been found in increasing concentrations in the aquatic environment. Fishes exposed to such metals have altered gene expression, serum profiles, tissue histology and bioindices that serve as overall health biomarkers. The heavy metals (Ni, Cd, and Cr) accumulated in water and fish tissues, were beyond the permissible limits defined by the Central Pollution Control Board/World Health Organization. Metallothionein (MT) and glutathione peroxidase (GPX) genes expression patterns highlighted the metal-specific exposure of fish. An increased fold change of genes against beta-actin serves as a potential feature for toxicity. Metal toxicity is also reflected by an increased level of digestive enzymes (amylase and lipase) in the serum and alterations in values of reproductive hormones (11-Ketotestosterone and progesterone). Total serum bilirubin attribute to the liver and biliary tract disease in fishes. Histopathological studies show cellular degeneration, breakage, vacuolization signifying the chronic stress.
اظهر المزيد [+] اقل [-]CYP1A mRNA expression in redeye mullets (Liza haematocheila) from Bohai Bay, China
2011
An, Lihui | Hu, Jianying | Yang, Min | Zheng, Binghui | Wei, An | Shang, Jingjing | Zhao, Xingru
Induction of cytochrome P4501A (CYP1A) has been used as a biomarker in fish for monitoring aromatic and organic contaminants. In this study, a partial of CYP1A gene in redeye mullet (Liza haematocheila) was isolated and sequenced, and then a real-time quantitative reverse-transcription polymerase chain reaction assay was developed for quantification of CYP1A mRNA normalized to β-actin. The developed method was applied to detect CYP1A mRNA expression in redeye mullets collected from Nandaihe (reference site) and Dashentang (impacted site) in Bohai Bay, China. CYP1A mRNA expression values were significantly elevated in redeye mullets from Dashentang compared to a reference site – Nandaihe, which was correlated with the contents of different environmentally relevant pollutants in tissues, particularly with PCBs and PBDEs.
اظهر المزيد [+] اقل [-]Investigation into the role of Stmn2 in vascular smooth muscle phenotype transformation during vascular injury via RNA sequencing and experimental validation
2022
Ke, Xiao | Guo, Wenyu | Peng, Yanren | Feng, Zongming | Huang, Yi-teng | Deng, Ming | Wei, Min-xin | Wang, Zan-xin
This study examined the effects of Stmn2 on phenotype transformation of vascular smooth muscle in vascular injury via RNA sequencing and experimental validation. Total RNA was extracted for RNA sequencing after 1, 3 and 5 days of injury to screen the differentially expressed genes (DEGs). Western blot was used to detect the protein expression of Stmn2 and its associated targets. The morphological changes of carotid arteries in rats were examined by hematoxylin and eosin (H&E) staining. The expression of vascular smooth muscle cell (VSMC) phenotype markers smooth muscle alpha-actin (α-SMA), vimentin and OPN were detected by immunohistochemistry. DEGs were related to the extracellular matrix and other cell components outside the plasma membrane. They were associated with protein binding, cytoskeleton protein binding, signal receptor binding and other molecular functions, actin cytoskeleton regulation and other Kyoto Encyclopedia of Genes and Genomes pathways. Stmn2 was identified as the hub gene of actin cytoskeleton pathway and vascular disease, and its expression followed the trend of decreasing initially and increasing afterwards during the progress of vascular injury. Western blot assay showed that the expression of Stmn2 and Tubulin decreased immediately after vascular injury; Stmn2 overexpression significantly up-regulated the expression of osteopontin and α-SMA and vimentin in VSMCs. The results of morphology analysis and immunostaining also showed that Stmn2 overexpression promoted the intima thickening and enhanced the proliferating cell nuclear antigen expression in the injured vascular tissues. In conclusion, our results implied that Stmn2 may play a potential role in vascular injury, which may be associated with VSMC phenotype transformation. Further studies are warranted to determine detailed molecular mechanisms of Stmn2 in vascular injury.
اظهر المزيد [+] اقل [-]