Human & experimental toxicology最新文献_第3页

Gpnmb silencing protects against hyperoxia-induced acute lung injury by inhibition of mitochondrial-mediated apoptosis. 沉默 Gpnmb 可通过抑制线粒体介导的细胞凋亡防止高氧诱导的急性肺损伤。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271231222873

Xiaoqin Wang, Song Qin, Yingcong Ren, Banghai Feng, Junya Liu, Kun Yu, Hong Yu, Zhenliang Liao, Hong Mei, Mei Tan

{"title":"Gpnmb silencing protects against hyperoxia-induced acute lung injury by inhibition of mitochondrial-mediated apoptosis.","authors":"Xiaoqin Wang, Song Qin, Yingcong Ren, Banghai Feng, Junya Liu, Kun Yu, Hong Yu, Zhenliang Liao, Hong Mei, Mei Tan","doi":"10.1177/09603271231222873","DOIUrl":"10.1177/09603271231222873","url":null,"abstract":"Background: Hyperoxia-induced acute lung injury (HALI) is a complication to ventilation in patients with respiratory failure, which can lead to acute inflammatory lung injury and chronic lung disease. The aim of this study was to integrate bioinformatics analysis to identify key genes associated with HALI and validate their role in H2O2-induced cell injury model.Methods: Integrated bioinformatics analysis was performed to screen vital genes involved in hyperoxia-induced lung injury (HLI). CCK-8 and flow cytometry assays were performed to assess cell viability and apoptosis. Western blotting was performed to assess protein expression.Results: In this study, glycoprotein non-metastatic melanoma protein B (Gpnmb) was identified as a key gene in HLI by integrated bioinformatics analysis of 4 Gene Expression Omnibus (GEO) datasets (GSE97804, GSE51039, GSE76301 and GSE87350). Knockdown of Gpnmb increased cell viability and decreased apoptosis in H2O2-treated MLE-12 cells, suggesting that Gpnmb was a proapoptotic gene during HALI. Western blotting results showed that knockdown of Gpnmb reduced the expression of Bcl-2 associated X (BAX) and cleaved-caspase 3, and increased the expression of Bcl-2 in H2O2 treated MLE-12 cells. Furthermore, Gpnmb knockdown could significantly reduce reactive oxygen species (ROS) generation and improve the mitochondrial membrane potential.Conclusion: The present study showed that knockdown of Gpnmb may protect against HLI by repressing mitochondrial-mediated apoptosis.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271231222873"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139081181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of combined exposure of manganese and iron on serum inflammatory factor levels among workers. 锰和铁的综合接触对工人血清炎症因子水平的影响

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241293112

Dian-Yin Liang, Jian-Chao Peng, Bing-Yan Xie, Wen-Xia Qin, Michael Aschner, Shi-Yan Ou, Yue-Ming Jiang

引用次数: 0

Comparative analysis of noise and music exposure on inflammatory responses on lipopolysaccharide-induced septic rats. 噪音和音乐对脂多糖诱导的败血症大鼠炎症反应的比较分析

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241282584

Hu Liu, Xing-Guo Peng, Ran Gao, Kai Yang, Yan-Bo Zhao

{"title":"Comparative analysis of noise and music exposure on inflammatory responses on lipopolysaccharide-induced septic rats.","authors":"Hu Liu, Xing-Guo Peng, Ran Gao, Kai Yang, Yan-Bo Zhao","doi":"10.1177/09603271241282584","DOIUrl":"https://doi.org/10.1177/09603271241282584","url":null,"abstract":"Objective: Environmental factors such as noise and music can significantly impact physiological responses, including inflammation. This study explored how environmental factors like noise and music affect lipopolysaccharide (LPS)-induced inflammation, with a focus on systemic and organ-specific responses.Materials and methods: 24 Wistar rats were divided into four groups (n = 6 per group): Control group, LPS group, noise-exposed group, and music-exposed group. All rats, except for the Control group, received 10 mg/kg LPS intraperitoneally. The rats in the noise-exposed group were exposed to 95 dB noise, and the music-exposed group listened to Mozart's K. 448 music (65-75 dB) for 1 h daily over 7 days. An enzyme-linked immunosorbent assay was utilized to detect the levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), in serum and tissues (lung, liver, and kidney). Western blot examined the phosphorylation levels of nuclear factor-κB (NF-κB) p65 in organ tissues.Results: Compared with the Control group, LPS-induced sepsis rats displayed a significant increase in the levels of TNF-α and IL-1β in serum, lung, liver, and kidney tissues, as well as a remarkable elevation in the p-NF-κB p65 protein expression in lung, liver, and kidney tissues. Noise exposure further amplified these inflammatory markers, while music exposure reduced them in LPS-induced sepsis rats.Conclusion: Noise exposure exacerbates inflammation by activating the NF-κB pathway, leading to the up-regulation of inflammatory markers during sepsis. On the contrary, music exposure inhibits NF-κB signaling, indicating a potential therapeutic effect in reducing inflammation.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241282584"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effects of short-time air pollution, SO2, and ozone on biochemical, histo-pathological, oxidative stress, and carcinogenesis related genes expressions in the liver of the rats. 短时空气污染、二氧化硫和臭氧对大鼠肝脏生化、组织病理学、氧化应激和致癌相关基因表达的影响。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241263569

Bita Sepehri, Roya Darbani, Mehran Mesgari-Abbasi, Sorayya Kheirouri, Dariush Shanehbandi, Monireh Khordadmehr, Mohammad Alizadeh

{"title":"The effects of short-time air pollution, SO2, and ozone on biochemical, histo-pathological, oxidative stress, and carcinogenesis related genes expressions in the liver of the rats.","authors":"Bita Sepehri, Roya Darbani, Mehran Mesgari-Abbasi, Sorayya Kheirouri, Dariush Shanehbandi, Monireh Khordadmehr, Mohammad Alizadeh","doi":"10.1177/09603271241263569","DOIUrl":"https://doi.org/10.1177/09603271241263569","url":null,"abstract":"Objective of the research: Air pollution is a universal issue and has significant deleterious effects on both human health and also environment. The important indicators of air pollution include ozone (O3), particulate matter (PM), nitrogen dioxide (NO2), and sulfur dioxide (SO2). This research aims to investigate the impacts of ambient air pollution (AAP), SO2, and O3 on oxidative stress parameters, liver tissue histopathology, and expression of some carcinogenesis-related genes in the hepatic tissue of rats.Materials and methods: 32 Wistar rats were randomly allocated to four groups: the control group, the AAP group, the SO2 group (10 ppm), and the ozone group (0.6 ppm). Over a period of five consecutive weeks, the rats were exposed to the specified pollutants for 3 h daily; liver tissues were harvested and instantly fixed with formalin. Pathological changes were assessed in the tissue samples. Additionally, the RT-qPCR technique was utilized to investigate Expression alterations of BAX, p-53, BCL2, caspase-3, caspase-8 and caspase-9. Furthermore, 30 milligrams of hepatic tissues were extracted to assess the activities of oxidative stress enzymes.Results: The liver catalase and MDA activity were elevated in the air pollution (p < .05). Also, liver GPx activity in air pollution and ozone groups was significant in comparison to the control group (p < .05). The SO2 group exhibited severe lesions in histopathology examinations.Conclusions: The findings revealed an alteration in liver histopathology, an induction of oxidative stress, and the expression of some apoptosis-related genes in hepatic tissues after exposure to AAP, SO2, and O3.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241263569"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141790628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alkylating agents are possible inducers of glioblastoma and other brain tumors. 烷化剂可能会诱发胶质母细胞瘤和其他脑肿瘤。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241256598

Carr J Smith, Thomas A Perfetti, Chirayu Chokshi, Chitra Venugopal, J Wesson Ashford, Sheila K Singh

{"title":"Alkylating agents are possible inducers of glioblastoma and other brain tumors.","authors":"Carr J Smith, Thomas A Perfetti, Chirayu Chokshi, Chitra Venugopal, J Wesson Ashford, Sheila K Singh","doi":"10.1177/09603271241256598","DOIUrl":"10.1177/09603271241256598","url":null,"abstract":"Epidemiological evidence of an association between exposure to chemical carcinogens and an increased risk for development of glioblastoma (GBM) is limited to weak statistical associations in cohorts of firefighters, farmers, residents exposed to air pollution, and soldiers exposed to toxic chemicals (e.g., military burn pits, oil-well fire smoke). A history of ionizing radiation therapy to the head or neck is associated with an increased risk of GBM. Ionizing radiation induces point mutations, frameshift mutations, double-strand breaks, and chromosomal insertions or deletions. Mutational profiles associated with chemical exposures overlap with the broad mutational patterns seen with ionizing radiation. Data on 16 agents (15 chemicals and radio frequency radiation) that induced tumors in the rodent brain were extracted from 602 Technical Reports on 2-years cancer bioassays found in the National Toxicology Program database. Ten of the 15 chemical agents that induce brain tumors are alkylating agents. Three of the 15 chemical agents have idiosyncratic structures and might be alkylating agents. Only two of the 15 chemical agents are definitively not alkylating agents. The rat model is thought to be of possible relevance to humans suggesting that exposure to alkylating chemicals should be considered in epidemiology studies on GBM and other brain tumors.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241256598"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Widely targeted quantitative lipidomics reveal lipid remodeling in adipose tissue after long term of the combined exposure to bisphenol A and fructose. 广泛的靶向定量脂质组学揭示了长期接触双酚 A 和果糖后脂肪组织的脂质重塑。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241232609

Yonghong Tang, Guifang Ou, Ouyan Rang, Xu Liu, Xiaocheng Liu, Xinru Qin, Guojuan Li, Qing Yang, Mu Wang

{"title":"Widely targeted quantitative lipidomics reveal lipid remodeling in adipose tissue after long term of the combined exposure to bisphenol A and fructose.","authors":"Yonghong Tang, Guifang Ou, Ouyan Rang, Xu Liu, Xiaocheng Liu, Xinru Qin, Guojuan Li, Qing Yang, Mu Wang","doi":"10.1177/09603271241232609","DOIUrl":"10.1177/09603271241232609","url":null,"abstract":"Adipose tissue is the main organ that stores lipids and it plays important roles in metabolic balance in the body. We recently reported in Human and Experimental Toxicology that the combined exposure to BPA and fructose may interfere with energy metabolism of adipose tissue. However, it is still unclear whether the combined exposure to BPA and fructose has the possibility to induce lipid remodeling in adipose tissue. In the present study, we performed a widely targeted quantitative lipidomic analysis of the adipose tissue of rats after 6 months of BPA and fructose combined exposure. We totally determined 734 lipid molecules in the adipose tissue of rats. Principal component analysis (PCA) showed the group of the combined exposure to higher-dose (25 μg/kg every other day) BPA and fructose can be distinguished from the groups of control, higher-dose BPA exposure and fructose exposure clearly. Partial least squares-discriminant analysis (PLS-DA) and univariate statistical analysis displayed lipids of PC(18:0_ 20:3), TG(8:0_14:0_16:0), TG(12:0_14:0_16:1), TG(10:0_16:0_16:1), TG(12:0_ 14:0_18:1), TG(14:0_ 16:0_16:1), TG(14:0_14:1_16:1), TG(8:0_ 16:1_16:2), TG(14:1_16:1_ 16:1), TG(16:1_18:1_18:1), TG(16:0_16:1_20:4) and TG(15:0_18:1_ 24:1) may contributed the most to the discrimination. These findings indicated that combined exposure to BPA and fructose has the potential to cause lipid remodeling in adipose tissue.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241232609"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139699164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

YTHDF1-mediated sphingosine kinase 2 upregulation alleviates bupivacaine-induced neurotoxicity via the PI3K/AKT axis. YTHDF1介导的鞘氨醇激酶2上调可通过PI3K/AKT轴减轻布比卡因诱导的神经毒性。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271231218707

Ru Yuan, Chunxia Wu

{"title":"YTHDF1-mediated sphingosine kinase 2 upregulation alleviates bupivacaine-induced neurotoxicity via the PI3K/AKT axis.","authors":"Ru Yuan, Chunxia Wu","doi":"10.1177/09603271231218707","DOIUrl":"10.1177/09603271231218707","url":null,"abstract":"Background: Bupivacaine (BUP), a long-acting local anesthetic, has been widely used in analgesia and anesthesia. However, evidence strongly suggests that excessive application of BUP may lead to neurotoxicity in neurons. Sphingosine kinase 2 (SPHK2) has been reported to exert neuroprotective effects. In this study, we intended to investigate the potential role and mechanism of SPHK2 in BUP-induced neurotoxicity in dorsal root ganglion (DRG) neurons.Methods: DRG neurons were cultured with BUP to simulate BUP-induced neurotoxicity in vitro. CCK-8, LDH, and flow cytometry assays were performed to detect the viability, LDH activity, and apoptosis of DRG neurons. RT-qPCR and western blotting was applied to measure gene and protein expression. Levels. MeRIP-qPCR was applied for quantification of m6A modification. RIP-qPCR was used to analyze the interaction between SPHK2 and YTHDF1.Results: SPHK2 expression significantly declined in DRG neurons upon exposure to BUP. BUP challenge substantially reduced the cell viability and increased the apoptosis rate in DRG neurons, which was partly abolished by SPHK2 upregulation. YTHDF1, an N6-methyladenosine (m6A) reader, promoted SPHK2 expression in BUP-treated DRG neurons in an m6A-dependent manner. YTHDF1 knockdown partly eliminated the increase in SPHK2 protein level and the protection against BUP-triggered neurotoxicity in DRG neurons mediated by SPHK2 overexpression. Moreover, SPHK2 activated the PI3K/AKT signaling to protect against BUP-induced cytotoxic effects on DRG neurons.Conclusions: In sum, YTHDF1-mediated SPHK2 upregulation ameliorated BUP-induced neurotoxicity in DRG neurons via promoting activation of the PI3K/AKT signaling pathway.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271231218707"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparing the acute toxicities of co-exposure to cocaine and ethanol versus cocaine alone. 比较同时暴露于可卡因和乙醇与单独暴露于可卡因的急性毒性。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241269024

Kwun Lok Cheung, Rex Pui Kin Lam, Chi Keung Chan, Man Li Tse, Matthew Sik Hon Tsui, Timothy Hudson Rainer

{"title":"Comparing the acute toxicities of co-exposure to cocaine and ethanol versus cocaine alone.","authors":"Kwun Lok Cheung, Rex Pui Kin Lam, Chi Keung Chan, Man Li Tse, Matthew Sik Hon Tsui, Timothy Hudson Rainer","doi":"10.1177/09603271241269024","DOIUrl":"https://doi.org/10.1177/09603271241269024","url":null,"abstract":"Introduction: Cocaine is commonly consumed with ethanol, which leads to the formation of cocaethylene through transesterification. Cocaethylene is an active metabolite of cocaine with a longer duration of action. Literature on the combined toxicity of cocaine, ethanol, and cocaethylene is conflicting. We aimed to compare the acute toxicities of co-exposure to cocaine and ethanol versus cocaine alone in Hong Kong.Methods: This was a retrospective study on acute cocaine toxicities reported to the Hong Kong Poison Control Center from 1 January 2010 to 22 January 2023. Cocaine exposure was confirmed by urine immunoassays/laboratory tests and ethanol co-ingestion was confirmed by blood ethanol concentrations. A serious outcome was defined as a National Poison Data System outcome moderate or above. Univariate analyses and multivariable logistic regression were performed to compare the associations of clinical outcomes with and without ethanol, followed by subgroup analyses of cases with complete data.Results: We analyzed 109 patients (median age 29 years, 71% men, 68% Chinese), of whom 20 had confirmed ethanol co-ingestion (mean blood ethanol concentration 1350 mg/L). Multivariable analysis showed that co-exposure to cocaine and ethanol was associated with a lower risk of serious outcomes (adjusted odds ratio 0.09, 95% confidence interval 0.01-0.77; p = 0.03) after adjusting for age, sex, ethnicity, route of cocaine administration, and physical health status. Subgroup analyses showed similar findings.Conclusions: In contrast to previous studies, we did not identify a higher risk of serious outcomes after co-exposure to cocaine and ethanol compared to cocaine alone in a predominantly Chinese cohort.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241269024"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KLF6 silencing attenuates MCAO-induced brain injury and cognitive dysfunction via targeting ferroptosis and activating the Nrf2/HO-1 pathway.

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241304372

Hongyu Qian, Sufang Zhou, Rong Qian, Qingye Li, Jian Zhang, Yanbing Ding, Chuanxiang Wang

{"title":"KLF6 silencing attenuates MCAO-induced brain injury and cognitive dysfunction via targeting ferroptosis and activating the Nrf2/HO-1 pathway.","authors":"Hongyu Qian, Sufang Zhou, Rong Qian, Qingye Li, Jian Zhang, Yanbing Ding, Chuanxiang Wang","doi":"10.1177/09603271241304372","DOIUrl":"https://doi.org/10.1177/09603271241304372","url":null,"abstract":"Introduction: The incidence of cerebral ischemia-reperfusion injury (I/R) is complex which seriously threatens the life safety of patients. Neither its prevention nor its treatment has been successful so far. Proteins that bind to DNA and belong to the C2/H2 zinc finger family are known as Krüppel-like factors (KLFs). Among them, KLF6 plays a vital role in proliferation, metabolism, inflammation, and damage responses, although its function in I/R remains largely unexplored.Methods: In this study, we induced cerebral ischemia in rats using the middle cerebral artery occlusion (MCAO) model. Neural function, cerebral infarction volume, cognitive function, cortical pathological lesions, ferroptosis, and oxidative stress were measured.Results: Our findings indicated that the MCAO model exhibited signs of ferroptosis and a concurrent increase in KLF6 levels. Inhibition of KLF6 resulted in a significant decrease in the escape latency during swimming tests (p < .05), an increase in the frequency of platform crossings, and prolonged duration in the target quadrant compared to the control group. Additionally, silencing KLF6 mitigated MCAO-induced brain injury and reduced oxidative stress and ferroptosis, as evidenced by altered levels of Nrf2/HO-1 signaling proteins.Discussion: In conclusion, our results suggest that silencing KLF6 may protect against MCAO-induced pyroptosis, oxidative stress, and neurological dysfunction by inactivating the Nrf2/HO-1 signaling pathway. This study offers new perspectives on the molecular mechanisms related to MCAO and emphasizes the significance of targeting KLF6 for future therapeutic approaches.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241304372"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Arsenic-induced downregulation of BRWD3 suppresses proliferation and induces apoptosis in lung adenocarcinoma cells through the p53 and p65 pathways. 砷诱导的 BRWD3 下调可通过 p53 和 p65 途径抑制肺腺癌细胞的增殖并诱导其凋亡。

Human & experimental toxicology Pub Date : 2024-01-01 DOI: 10.1177/09603271241279166

Yanhua Zhu, Mei Xiao, Ruihuan Zhao, Xuefei Yang, Kun Wu, Xiao Liu, Xi Chen, Lei Guo, Jiezhen Liu, Xu Chen, Na Liu, Yuefeng He, Yanliang Zhang

{"title":"Arsenic-induced downregulation of BRWD3 suppresses proliferation and induces apoptosis in lung adenocarcinoma cells through the p53 and p65 pathways.","authors":"Yanhua Zhu, Mei Xiao, Ruihuan Zhao, Xuefei Yang, Kun Wu, Xiao Liu, Xi Chen, Lei Guo, Jiezhen Liu, Xu Chen, Na Liu, Yuefeng He, Yanliang Zhang","doi":"10.1177/09603271241279166","DOIUrl":"10.1177/09603271241279166","url":null,"abstract":"Bromodomain and WD-repeat domain-containing protein 3 (BRWD3) exhibits high expression in lung adenocarcinoma (LUAD) tissues and cells; however, its function in arsenic-induced toxicological responses remains unclear. This study aimed to investigate BRWD3 expression in response to arsenic-induced conditions and its impact on the proliferation and apoptosis of LUAD cell line SPC-A1 upon BRWD3 knockdown. The results revealed a decrease in BRWD3 expression in SPC-A1 cells treated with sodium arsenite (NaAsO2), but not sodium arsenite's metabolites. BRWD3 knockdown suppressed cell proliferation and induced apoptosis in SPC-A1 cells. Western blot analysis revealed that BRWD3 knockdown resulted in the upregulation of p53, phospho-p53-Ser392, and its downstream factors including MDM2, Bak, and Bax. Additionally, we observed the downregulation of p65, phospho-p65-Ser276, phospho-p65-Ser536, and its downstream factors, including IκBα, BIRC3, XIAP and CIAP1. Moreover, polymerase chain reaction analysis showed that BRWD3 knockdown also resulted in the downregulation of proliferation-related genes and upregulation of apoptosis-related genes. In conclusion, BRWD3 mediated proliferation and apoptosis via the p53 and p65 pathways in response to arsenic exposure, suggesting potential implications for LUAD treatment through BRWD3 downregulation by arsenic.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"43 ","pages":"9603271241279166"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0