Biochemistry and Cell Biology
·
2024
·
IF 2.4
Xiang Chen,Yuan Yao,Guotong Gong,Tianji He,Chenjun Ma,Jingsong Yu
Prostate cancer (PCa) is a complex disease with diverse molecular alterations. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that exhibits pleiotropic roles in PCa, and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent ligand for AhR. While targeting ferroptosis is an innovative PCa therapeutic strategy, the impact of AhR on this process remains unclear. This study aimed to investigate the influence of AhR on lipid peroxidation and ferroptosis. Results showed that TCDD activated AhR, as evidenced by increased CYP1A1 expression, leading to reduced cell viability. TCDD caused mitochondria shrinkage, decreased the GSH/GSSG ratio, and elevated the MDA levels and lipid peroxidation. Interestingly, AhR knockdown reversed these effects, similar to the action of ferroptosis inhibitors. Mechanistically, TCDD suppressed nuclear receptor subfamily 4 group A member 1 (NR4A1) expression, in part due to AhR activation. This suppression subsequently led to a reduction in the expression of the NR4A1 downstream target stearoyl-CoA desaturase 1 (SCD1). NR4A1 overexpression counteracted the effects of TCDD. In vivo, TCDD activated AhR, downregulated NR4A1 and SCD1 expression, induced mitochondria shrinkage, and increased the MDA and 4-hydroxynonenal (4-HNE) levels. In summary, TCDD promotes ferroptosis in androgen-dependent PCa via inhibiting the NR4A1/SCD1 axis, in part dependent on AhR activation.
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2017
·
IF 6.065
Shao-Lin Xie,Muhammad Junaid,Wan-Ping Bian,Juan-Juan Luo,Jabir Hussain Syed,Chao Wang,Wen-Xu Xiong,Yan-Bo Ma,Aping Niu,Xiao-Jun Yang,Ji-Xing Zou,De-Sheng Pei
The polycyclic aromatic hydrocarbons (PAHs) and 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) are classified as human carcinogens, and can also cause serious health problems. To develop a convenient bio-monitoring tool for the detection of PAHs and TCDD in the environment, we generated a transgenic zebrafish line Tg(cyp1a:mCherry) with cyp1a promoter driving mCherry expression. Here, Tg(cyp1a:mCherry) embryos were treated with different concentrations of TCDD and five US EPA priority PAHs congeners. The results showed that the expressions of mCherry and endogenous cyp1a were consistent with the PAHs exposure concentrations and were largely induced by TCDD and ≥4-ring PAHs. Moreover, the sensitivity of Tg(cyp1a:mCherry) embryos was also evaluated through monitoring of the PAHs contamination in the water and soil samples. The elevated red fluorescent signals and cyp1a expression levels were observed in Tg(cyp1a:mCherry) zebrafish after exposure to water samples and soil organic extracts with higher concentrations of ≥4-ring PAHs. These results further strengthen our findings of concentration- and congener-dependent response of the newly established zebrafish. Taken together, the newly established zebrafish line will prove as a sensitive, efficient and convenient tool for monitoring PAHs and TCDD contamination in the environment.
研究领域:
环境科学
·
毒理学
·
基因工程
·
水生生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2023
·
IF 6.8
Shaolin Xie,Bing Yang,Siying Li,Liangjun Ge,Min Li,Qingshi Chen,Xian Qing,Jixing Zou
CYP1A is the most commonly used biomarker and transgenic fish which carrying a cyp1a promoter to drive a reporter gene can be used as reliable way to monitor dioxin/dioxin-like compounds (DLCs) in the environment. Here, we cloned the cyp1a promoter of Gambusia affinis and this promoter showed stronger transcriptional activity than that of zebrafish. Then, a Tg(GAcyp1a:eGFP/Luc) transgenic zebrafish line was first constructed with the G. affinis cyp1a promoter driving eGFP expression using meganuclease I-SceI mediated transgenesis technology. The Tg(GAcyp1a:eGFP/Luc) larvae at 72 h post-fertilization (hpf) were tested by exposing to TCDD for 72 h, and induced GFP was mainly expressed in the liver with low background. The Tg(GAcyp1a:eGFP/Luc) zebrafish showed high sensitivity (limit of detection of 0.322 ng/L TCDD and 0.7 TEQ-ng/L PCDD/Fs) and specificity (insensitive to responses to PAHs and PCBs). In addition, the transgenic line showed a low detection concentration of the DLCs contaminated environmental samples (as low as 1.8 TEQ-ng/L), and the eGFP fluorescence intensity and the chemical-TEQ values were closely correlated. In conclusion, a sensitively and specifically transgenic zebrafish line was established to convenient and effective to detect DLCs in the environment.
研究领域:
环境科学
·
分子生物学
·
毒理学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2020
·Vol. 55
·期 16
·7029-7038
·
IF 3.553
Li Jingwen,Wang Wen,Xie Chengbei,Jia Qin,Yan Changchun,Yao Yue,Fang Zheng,Duan Lingfeng,Cheng Jie,Qu Lulu,Han Caiqin
2,3,7,8-Tetrachlorodibenzo- p -dioxin (TCDD) is a highly toxic persistent organic pollutant (POP) that can remain present in the environment for a long time. Prolonged exposure to TCDD may bring about a wide variety of deleterious health effects to humans. Based on these circumstances, a rapid and facile surface-enhanced Raman scattering (SERS) method with gold nanoparticle-modified silver nanorod (AuNP@AgNR) substrates was developed for detection of 2,3,7,8-TCDD. Compared with SERS-active gold nanoparticles and silver nanorod substrate, the prepared AuNP@AgNR substrate showed an outstanding SERS performance with an enhancement factor of up to 2.4 × 10 8 . Furthermore, using AuNP@AgNR as a SERS substrate, we achieved the highly sensitive detection of 2,3,7,8-TCDD, and a density functional theory calculation was 6 to assign the characteristic peaks of 2,3,7,8-TCDD. The reliable linear range was determined to be 10 ng mL −1 to 10 μg mL −1 , with the limit of detection and the limit of quantitation as low as 7.1 and 8.2 ng mL −1 , respectively. By this method, the recovery rates of 2,3,7,8-TCDD spiked in the river samples were 82.3–97.4% with a relative standard deviation between 1.9 and 8.4%. These results show that the AuNP@AgNR substrate can be used for highly sensitive detection of 2,3,7,8-TCDD and has potential applications in the detection of other POPs.
研究领域:
环境科学
·
分析化学
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2024
·
IF 8
Yingying Liang,Hailin Liu,Lin Wang,Jing Zhao,Shunyi Li,Li Yi,Sijing Jiang,Zhenghui Lu,Guimin Zhang
Dioxin-like compounds (DLCs) are environmental xenobiotics that can activate the aryl hydrocarbon receptors (AhR), thereby imposing a significant threat to human health through biomagnifications processes. In this study, a dioxin-activated nano-luminescent Saccharomyces cerevisiae bioreporter, called DnaSc, was developed for simple and rapid detection of DLCs and AhR agonists. The bioreporter used nano-luciferase (NLuc) as a signal generator to emit bioluminescent signals in response to DLCs without cell lysis. Through optimizing AhR nuclear translocator (ARNT) expression and engineering the AhR, the yeast-based bioassay exhibited a detection limit of 10 fM for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within 6 h, making it the most sensitive whole-cell biosensor reported to date. Furthermore, the detection capacity of the dioxin-activated nano-luminescent S. cerevisiae bioreporter (DnaSc) bioassay for DLCs and AhR agonists was characterized. In summary, the yeast-based bioreporter developed in this study provided a simple, sensitive, and cost-effective method for DLCs detection.
研究领域:
环境科学
·
毒理学
·
生物技术
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Chao Wang,Xiaoxin Liu,Junqiu Zhai,Chunfei Zhong,Haishen Zeng,Longkuan Feng,Yunyun Yang,Xinyan Li,Mei Ma,Tiangang Luan,Jiewei Deng
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic persistent organic pollutant (POP) that can induce DNA damage within cells. Although oxidative stress is one of the primary mechanisms causing DNA damage, its role in the process of TCDD-induced DNA damage remains unclear. In this study, the TCDD-induced production of reactive oxygen species (ROS) and the occurrence of DNA damage at the AP site were monitored simultaneously. Further investigation revealed that TCDD impaired the activities of superoxide dismutase (SOD) and catalase (CAT), compromising the cellular antioxidant defense system. Consequently, this led to an increase in the production of O 2 .− and NO, thus inducing DNA damage at the AP site under oxidative stress. Our findings were further substantiated by the upregulation of key genes in the base excision repair (BER) pathway and the absence of DNA AP site damage after inhibiting O 2 .− and NO. In addition, transcriptome sequencing revealed that TCDD induces DNA damage by upregulating genes associated with oxidative stress in the mitogen-activated protein kinase (MAPK), cyclic adenosine monophosphate (cAMP), and breast cancer pathways. This study provides important insights into the toxicity mechanisms of TCDD.
研究领域:
毒理学
·
分子生物学
·
遗传学
✓ 已验证
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）