TOXICOLOGY
·
2024
·
IF 4.8
Di Ouyang,Yiren Xiong,Zuqing Hu,Jiayi He,Shanshan He,Renyi Liu,Zhenjie Gao,Dalin Hu
The mechanistic target of rapamycin (RAPA) complex 1 (mTORC1) - transcription factor EB (TFEB) pathway plays a crucial role in response to nutritional status, energy and environmental stress for maintaining cellular homeostasis. But there is few reports on its role in the toxic effects of arsenic exposure and the related mechanisms. Here, we show that the exposure of bronchial epithelial cells (BEAS-2B) to sodium arsenite promoted the activation of mTORC1 (p-mTORC1) and the inactivation of TFEB (p-TFEB), the number and activity of lysosomes decreased, the content of reduced glutathione (GSH) and superoxide dismutase (SOD) decreased, the content of malondialdehyde (MDA) increased, the DNA and chromosome damage elevated. Further, when mTORC1 was inhibited with RAPA, p-mTORC1 and p-TFEB down-regulated, GSH and SOD increased, MDA decreased, the DNA and chromosome damage reduced significantly, as compared with the control group. Our data revealed for the first time that mTORC1 - TFEB pathway was involved in sodium arsenite induced lysosomal alteration, oxidative stress and genetic damage in BEAS-2B cells, and it may be a potential intervention target for the toxic effects of arsenic.
研究领域:
毒理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2021
·
IF 6.025
Bangrong Cai,Mengya Liu,Jinxing Li,Dujuan Xu,Jiansheng Li
Chronic obstructive pulmonary disease (COPD) is widely recognized as a global public health problem and the third leading cause of mortality worldwide by 2020. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a dual-specificity protein and lipid phosphatase that plays an important role in COPD. However, the redox regulation of PTEN in the development of COPD was poorly studied. Our results showed that cigarette smoke extract (CSE) could oxidize PTEN in a time-dependent manner in BEAS-2B cells, whereas PTEN oxidation exposed to CSE was delayed compared to that of H 2 O 2. Additionally, we found that ROS derived from DUOX1 and 2 of NADPH oxidases were mainly responsible for oxidative inactivation PTEN, also simultaneously led to Trx-1 inactivation by dimerization . Oxidative mechanism of PTEN exposed to CSE was mediated by forming a disulfide bond between Cys 71 and Cys 124 , similar to H 2 O 2 . Inactivation of PTEN resulted in the increased phosphorylation of Akt. In conclusion, CSE exposure could elevate the intracellular ROS mainly from DUOX1 and 2 to oxidize PTEN and Trx-1 resulting in Akt activation, eventually cause the occurrence of COPD, suggesting that PTEN is a potential target for new therapies in COPD.
研究领域:
肺科学
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分子生物学
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细胞生物学
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氧化应激
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药理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2021
·Vol. 47
·期 4
·1-1
·
IF 4.101
Shuo Yang,Xiao-Long Huang,Jin Chen,Li-Na Mao,Xu Liu,Wen-Sheng Yuan,Xiao-Jie Wu,Guang-Wei Luo
Fine particulate matter (PM2.5) with an average aerodynamic diameter of <2.5 µm can cause severe lung injury. Oxidative stress and inflammation are considered the main outcomes of PM2.5 exposure. Curcumin is a well‑known antioxidant; however, its effect on PM2.5‑induced oxidative injury in airway epithelial cells remains unclear. In the present study, it was demonstrated that pre‑treatment with curcumin significantly reduced the PM2.5‑induced apoptosis of BEAS‑2B human bronchial epithelial cells by decreasing the level of intercellular reactive oxygen species. Western blot analysis revealed that curcumin increased the expression of nuclear factor erythroid 2‑related factor 2 (NRF2) and regulated the transcription of downstream genes, particularly those encoding antioxidant enzymes. Moreover, curcumin reduced the PM2.5‑induced expression and production of inflammatory factors, and induced the expression of the anti‑inflammatory factors, interleukin (IL)‑5 and IL‑13. Taken together, the present study demonstrates that curcumin protects BEAS‑2B cells against PM2.5‑induced oxidative damage and inflammation, and prevents cell apoptosis by increasing the activation of NRF2‑related pathways. It is thus suggested that curcumin may be a potential compound for use in the prevention of PM2.5‑induced tissue injury.
研究领域:
药理学
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毒理学
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细胞生物学
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环境健康
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DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2023
·Vol. 30
·期 32
·79423-79436
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IF 5.8
Zhang Jingni,Wang Hongjuan,Chen Huan,Liu Yong,Wang An,Hou Hongwei,Hu Qingyuan
Long-term use of alcohol and cigarettes is associated with millions of deaths each year, directly or indirectly. The carcinogen acetaldehyde is both a metabolite of alcohol and the most abundant carbonyl compound in cigarette smoke, and co-exposure of them is usual and primarily leads to liver and lung injury, respectively. However, few studies have explored the synchronic risk of acetaldehyde on the liver and lung. Here, we investigated the toxic effects and related mechanisms of acetaldehyde based on normal hepatocytes and lung cells. The results showed that acetaldehyde caused significant dose-dependent increases of cytotoxicity, ROS level, DNA adduct level, DNA single/double-strand breakage, and chromosomal damage in BEAS-2B cells and HHSteCs, with similar effects at the same doses. The gene and protein expression and phosphorylation of p38MAPK, ERK, PI3K, and AKT, key proteins of MAPK/ERK and PI3K/AKT pathways regulating cell survival and tumorigenesis, were significantly upregulated on BEAS-2B cells, while only protein expression and phosphorylation of ERK were upregulated significantly, the other three decreased in HHSteCs. When either the inhibitor of the four key proteins was co-treated with acetaldehyde, cell viabilities were almost unchanged in BEAS-2B cells and HHSteCs. Thus, acetaldehyde could synchronically induce similar toxic effects in BEAS-2B cells and HHSteCs, and MAPK/ERK and PI3K/AKT pathways seem to be involved in different regulatory mechanisms.
研究领域:
毒理学
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细胞生物学
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分子生物学
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致癌机制
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DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2021
·
IF 6.025
Dan Liu,Ye Cheng,Junliang Chen,Xueying Mei,Zhipeng Tang,Xiangyu Cao,Jianli Liu
Acrolein is a highly reactive unsaturated hazardous air pollutant , which is extremely irritating to the respiratory tract. Luteolin , an active flavonoid compound, possesses multiple biological activities . The purpose of this study was to evaluate the mechanism of the inhibition of acrolein-induced human bronchial epithelial (BEAS-2B) cells cytotoxicity by luteolin using network pharmacology and cell biology technology . Firstly, network pharmacology results indicated that oxidative stress processes might play an important role in luteolin inhibiting lung injury. Next, it was verified at the cellular level. Reactive oxygen species (ROS) generation increased, glutathione (GSH) level decreased after exposure to acrolein. MAPK signaling pathways were activated, which activated downstream IκBα/NF-κB signaling pathways. Meanwhile, acrolein caused oxidative DNA damage and double-strand breaks, induced DNA damage response (DDR) and apoptosis . These adverse effects were significantly reversed by luteolin, which inhibited the activation of MAPK/IκBα/NF-κB and DDR pathways, and reduced the ratio of Bax/Bcl-2. Moreover, luteolin also had a similar effect to antioxidant N-acetyl cysteine (NAC) in the regulation of signaling transduction mechanisms, which indicated that the regulation of oxidative stress played an important role in the process. These results provide an experimental basis for elucidating the molecular mechanisms of the inhibition of acrolein-induced BEAS-2B cytotoxicity with luteolin.
研究领域:
药理学
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细胞生物学
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分子生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2021
·
IF 4.221
Dan Liu,Ye Cheng,Zhipeng Tang,Xueying Mei,Xiangyu Cao,Jianli Liu
Acrolein is a hazardous air pollutant for humans and is responsible for many pulmonary diseases, but the underlying mechanisms have not been completely elucidated. This work is focused on the genotoxicity effects of human bronchial epithelial (BEAS-2B) cells induced by acrolein (20, 40, 80 μM). The molecular mechanism was investigated base on DNA damage and mitochondrial apoptosis pathways. The results showed that after exposure to acrolein, the cell viability, glutathione (GSH) of BEAS-2B cells were reduced. Reactive oxygen species (ROS) level significantly increased, accompanied by increased levels of DNA damage-related indicators 8-hydroxy-2 deoxyguanosine (8−OHdG), DNA content of comet tail (Tail DNA%), olive tail moment (OTM), and nucleus morphology. Cell arrested at the G2/M phase. Then, the DNA damage response (DDR) signaling pathway (Ataxia-telangiectasia-mutated (ATM) and Rad-3-related (ATR)/Chk1 and ATM/Chk2) and the consequent cell cycle checkpoints were activated. The expression of γ-H2AX was significantly increased, indicating that acrolein induced DNA double-strand breaks. Molecular docking assay showed that acrolein bound to DNA in a spontaneous process. Moreover, mitochondrial apoptosis pathway involved in apoptosis, mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) content of BEAS-2B cells were significantly reduced, and the apoptosis rate was significantly increased. The protein expression of Bax/Bcl-2 and Cleaved Caspase-3 were increased, and JNK signaling pathway was activated. All the results indicated that acrolein induced DNA damage, activated DDR and mitochondrial apoptosis pathways, which might be the pivotal factors to mediate cytotoxicity in BEAS-2B cells.
研究领域:
细胞生物学
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分子生物学
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毒理学
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环境健康
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产品关联
DOI
PubMed
高影响因子
Toxics
·
2025
·Vol. 13
·期 11
·987
·
IF 4.1
Yanan Zhang,Ziyu Xiao,Pu Mao,Fengrui Yang,Yingdi Ma,Bensen Xian,Mingming Fu,Guiying Li
Decabromodiphenyl ether (BDE209) has been widely used because of its excellent flame-retardant properties and ability. On the one hand, many studies have shown that the presence of BDE209 can potentially threaten human health and the environment. The production and processing of products containing BDE209 is prohibited except for special applications in China. On the other hand, the study of BDE209 on respiratory cells is not yet fully understood. Consequently, this study aims to investigate the mechanisms of toxic damage and oxidative stress induced by BDE209 exposure in lung epithelial Beas-2B cells. The proliferation of Beas-2B cells under BDE209 exposure was first analyzed by using a real-time label-free cell analyzer (RTCA). Then the cells’ morphological changes were observed using laser confocal microscopy. Subsequently, the effects of BDE209 exposure alone, combined exposure to N-acetylcysteine (NAC) and BDE209, on reactive oxygen species (ROS) levels and antioxidant defense-related factors in Beas-2B cells were analyzed separately. The results show that BDE209 exposure induces the proliferation of Beas-2B cells with a dose-dependent increase in inhibition. Microscopic observation of Beas-2B cells reveals significant damage and death. The levels of ROS are significantly increased ( p < 0.01), the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) are increased, the contents of catalase (CAT) are decreased, and the activities of glutathione peroxidase (GPX) are first decreased and then increased. However, under the co-exposure of NAC and BDE209, ROS levels are significantly reduced ( p < 0.01), MDA contents decrease, and SOD activities increase. In summary, BDE209 exposure leads to inhibition of Beas-2B cell proliferation, cellular morphology damage, increased ROS levels, and disturbances in antioxidant defense-related factors. The cells showed toxic damage and oxidative stress. In contrast, NAC can suppress ROS levels, enhance SOD activity, and inhibit GPX activity, thereby alleviating BDE209-induced cellular damage.
研究领域:
毒理学
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环境健康
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分子生物学
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呼吸毒理学
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氧化应激研究
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产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL TOXICOLOGY
·
2019
·Vol. 34
·期 6
·742-752
·
IF 2.649
Shijin Wu,Zhenzhen Zhu,Jialin Chen,Mei Wu,Lequan Qiu
Brominated flame retardants (BFRs) are supposed to act as disruptors of cell signaling, but the underlying mechanisms remain less clear. Human bronchial epithelial cells (BEAS-2B) were used to investigate the toxic effect and gene expression changes induced by tetrabromobisphenol A (TBBPA). By genome-wide approaches with Illumina RNA-seq, 87 genes were identified to exhibit ≥1.5-fold changes in expression after treatment by TBBPA for 48 h, among which, 79 were upregulated and 8 were downregulated. Gene ontology (GO) annotation enriched unigenes were divided into three clusters: biological process (BP), cellular component (CC) and molecular function (MF). Pathway analysis showed that NF-κB, TNF signaling, toll-like receptor, MAPK signaling and B-cell receptor were the most prominent pathways affected by TBBPA, which play key roles in regulating cell proliferation and cell differentiation, inflammatory response. Finally, for verifying the accuracy of microarray analysis, qRT-PCR was used to analyze the transcription level of key genes in the above signaling pathways, and ELISA assay confirmed the effect of TBBPA on the levels of CXCL-2, CCL-3, CCL-4, IL-1β, TNF-α, and IL-6. These findings provided important information for further exploitation of the mechanisms under-lying BFR-induced adverse health effects.
研究领域:
毒理学
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分子生物学
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环境健康科学
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DOI
PubMed
高影响因子
MACROMOLECULAR RAPID COMMUNICATIONS
·
2024
·
IF 4.2
Tao Wang,Chang Liu,Yu Li,Lifen Zhang,Zhenping Cheng
This work reports preparing thermal responsive poly ( N -isovinylcaprolactam) (PNVCL) microgel based films for cell growth and detachment. PNVCL microgels of hydrated size ranging from 386 to 815 nm (25 °C) and different crosslinking degree are prepared. The PNVCL microgels can be rapidly and massively deposited on glass by spin coating method. Atomic force microscopy (AFM) and water contact angle (WCA) are used to study the influence of crosslinking degree and particle size on the surface morphology, stability, and hydrophilicity of PNVCL microgel film. The cell activity of the desorbed cells is quantitatively characterized employing human normal lung epithelial cells (BEAS-2B). The results show that BEAS-2B cells can be desorbed quickly from the film in 30 min, and the optical density (OD) value of desorbed cells incubated after 3 d increases by approximately 52% compared to the control group. This study broadens the selection of temperature-sensitive film for cell harvesting, and provides a new tool for the quantitative characterization of desorbed cells.
研究领域:
材料科学
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生物医学工程
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Xiaoxiao Xu,Chuang Ma,Hang Wu,Yuanqiao Ma,Zejin Liu,Peijie Zhong,Chaolei Jin,Wenjuan Ning,Xiao Wu,Yijie Zhang,Jichang Han,Junpeng Wang
Fructose is a commonly used food additive and has many adverse effects on human health, but it is unclear whether fructose impacts pulmonary fibrosis. TGF-β1, a potent fibrotic inducer, is produced as latent complexes by various cells, including alveolar epithelial cells, macrophages, and fibroblasts, and must be activated by many factors such as reactive oxygen species (ROS). This study explored the impact of fructose on pulmonary fibrotic phenotype and epithelial-mesenchymal transition (EMT) using lung epithelial cells (A549 or BEAS-2B) and the underlying mechanisms. Fructose promoted the cell viability of lung epithelial cells, while N-Acetyl-l-cysteine (NAC) inhibited such. Co-treatment of fructose and latent TGF-β1 could induce the fibrosis phenotype and the epithelial-mesenchymal transition (EMT)-related protein expression, increasing lung epithelial cell migration and invasion. Mechanism analysis shows that fructose dose-dependently promoted the production of total and mitochondrial ROS in A549 cells, while NAC eliminated this promotion. Notably, post-administration with NAC or SB431542 (a potent TGF-β type I receptor inhibitor) inhibited fibrosis phenotype and EMT process of lung epithelial cells co-treated with fructose and latent TGF-β1. Finally, the fibrosis phenotype and EMT-related protein expression of lung epithelial cells were mediated by the ROS-activated latent TGF-β1/Smad3 signal. This study revealed that high fructose promoted the fibrotic phenotype of human lung epithelial cells by up-regulating oxidative stress, which enabled the latent form of TGF-β1 into activated TGF-β1, which provides help and reference for the diet adjustment of healthy people and patients with fibrosis.
研究领域:
肺科学
·
细胞生物学
·
分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2024
·Vol. 30
·期 1
·1-16
·
IF 6
Xie Bin,Chen Qiong,Dai Ziyu,Jiang Chen,Chen Xi
Background Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease associated with high morbidity and mortality worldwide. Oxidative injury and mitochondrial dysfunction in the airway epithelium are major events in COPD progression.Methods and resultsThe therapeutic effects of Progesterone (P4) were investigated in vivo and in vitro in this study. In vivo, in a cigarette smoke (CS) exposure-induced COPD mouse model, P4 treatment significantly ameliorated CS exposure-induced physiological and pathological characteristics, including inflammatory cell infiltration and oxidative injury, in a dose-dependent manner. The c-MYC/SIRT1/PGC-1α pathway is involved in the protective function of P4 against CS-induced COPD. In vitro, P4 co-treatment significantly ameliorated H2O2-induced oxidative injury and mitochondrial dysfunctions by promoting cell proliferation, increasing mitochondrial membrane potential, decreasing ROS levels and apoptosis, and increasing ATP content. Moreover, P4 co-treatment partially attenuated H2O2-caused inhibition in Nrf1, Tfam, Mfn1, PGR-B, c-MYC, SIRT1, and PGC-1α levels. In BEAS-2B and ASM cells, the c-MYC/SIRT1 axis regulated P4’s protective effects against H2O2-induced oxidative injury and mitochondrial dysfunctions.Conclusion P4 activates the c-MYC/SIRT1 axis, ameliorating CS-induced COPD and protecting both airway epithelial cells and smooth muscle cells against H2O2-induced oxidative damage. PGC-1α and downstream mitochondrial signaling pathways might be involved.
研究领域:
呼吸病学
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药理学
·
细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2019
·
IF 2.442
Nongping Zhong,Tao Dong,Zhongchun Chen,Yongwei Guo,Zhengzhong Shao,Xia Zhao
The functional epithelial regeneration is important for repairing tracheal defects. However, the potential of 3D-printed SF-based scaffolds for tracheal epithelial regeneration is still unknown. In this study, we developed a novel silk fibroin-based scaffold prepared by 3D printing of silk fibroin/hydroxypropyl methyl cellulose (SF/HPMC) thixotropic hydrogel and evaluated the tracheal epithelium proliferation on this scaffold in vitro. Combined with the freeze-dried technology, the 3D-printed SF/HPMC scaffolds had porous structures in the printed bars. After evaluation of their pore sizes, porosities, water contents and mechanical properties, the scaffolds were co-cultured with the normal human bronchial epithelial cell line (BEAS-2B) for seven days. We detected the BEAS-2B cells proliferation on the scaffolds using a CCK-8 assay, determined their mucin secretion and intercellular tight junction formation by immunofluorescence, as well as observed their cell viability and morphology by live/dead staining and scanning electronic microscopy. The results showed that the SF/HPMC scaffolds had good porosity, water content and mechanical properties. In addition, the BEAS-2B cells proliferated well on SF/HPMC scaffolds, during the seven-day co-culture, with high viability, mucin expression, and intercellular tight junction formation. In summary, these results demonstrated that the BEAS-2B cells could attach and proliferate on the 3D-printed SF/HPMC scaffolds, which were expected to have potential for facilitating tracheal epithelial regeneration.
研究领域:
生物医学工程
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组织工程
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）