المؤلفون: Juntao Yuan, Zhuoran Yu, Ping Zhang, Kai Luo, Ying Xu, Ting Lan, Min Zhang, Yingjie Chen, Zhongbing Lu

المصدر: Redox Biology, Vol 70, Iss , Pp 103080- (2024)

مصطلحات موضوعية: DDAH1, ADMA, Oxidative stress, PRDX1, SRXN1, Medicine (General), R5-920, Biology (General), QH301-705.5

الوصف: Growing evidence suggests that dimethylarginine dimethylaminohydrolase 1 (DDAH1), a crucial enzyme for the degradation of asymmetric dimethylarginine (ADMA), is closely related to oxidative stress during the development of multiple diseases. However, the underlying mechanism by which DDAH1 regulates the intracellular redox state remains unclear. In the present study, DDAH1 was shown to interact with peroxiredoxin 1 (PRDX1) and sulfiredoxin 1 (SRXN1), and these interactions could be enhanced by oxidative stress. In HepG2 cells, H2O2-induced downregulation of DDAH1 and accumulation of ADMA were attenuated by overexpression of PRDX1 or SRXN1 but exacerbated by knockdown of PRDX1 or SRXN1. On the other hand, DDAH1 also maintained the expression of PRDX1 and SRXN1 in H2O2-treated cells. Furthermore, global knockout of Ddah1 (Ddah1-/-) or liver-specific knockout of Ddah1 (Ddah1HKO) exacerbated, while overexpression of DDAH1 alleviated liver dysfunction, hepatic oxidative stress and downregulation of PRDX1 and SRXN1 in CCl4-treated mice. Overexpression of liver PRDX1 improved liver function, attenuated hepatic oxidative stress and DDAH1 downregulation, and diminished the differences between wild type and Ddah1-/- mice after CCl4 treatment. Collectively, our results suggest that the regulatory effect of DDAH1 on cellular redox homeostasis under stress conditions is due, at least in part, to the interaction with PRDX1 and SRXN1.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2213231724000569Test; https://doaj.org/toc/2213-2317Test

الوصول الحر: https://doaj.org/article/20be8b6c0082496a850e14b74c7ed757Test

المؤلفون: Xing Wang, Jiandi Yu, Huali Wen, Junfeng Yan, Kun Peng, Haiyong Zhou

المصدر: BMC Urology, Vol 23, Iss 1, Pp 1-13 (2023)

مصطلحات موضوعية: Prostate cancer, Radiotherapy, SRXN1, Antioxidant stress, Prognostic marker, Diseases of the genitourinary system. Urology, RC870-923

الوصف: Abstract Purpose To explore the mechanisms of radiotherapy resistance and search for prognostic biomarkers for prostate cancer. Methods The GSE192817 and TCGA PRAD datasets were selected and downloaded from the GEO and UCSC Xena databases. Differential expression and functional annotation analyses were applied to 52 tumour cell samples from GSE192817. Then, the ssGSEA or GSVA algorithms were applied to quantitatively score the biological functional activity of samples in the GSE192817 and TCGA PRAD datasets, combined with specific gene sets collected from the Molecular Signatures Database (MSigDB). Subsequently, the Wilcoxon rank-sum test was used to compare the differences in ssGSEA or GSVA scores among cell types or PRAD patients. Moreover, radiotherapy resistance-associated gene screening was performed on DU145 and PC3 cells (prostate cancer cells), and survival analysis was used to evaluate the efficacy of these genes for predicting the prognosis of PRAD patients. Results A total of 114 genes that were differentially expressed in more than two different cancer cell types and associated with either sham surgery or radiotherapy treatment (X-ray or photon irradiation) were detected in cancer cells from GSE192817. Comparison of DNA damage-related ssGSEA scores between sham surgery and radiotherapy treatment in prostate cancer cells (DU145 and PC3) showed that photon irradiation was potentially more effective than X-ray treatment. In the TCGA PRAD dataset, patients treated with radiotherapy had much higher “GOBP_CELLULAR_RESPONSE_TO_DNA_DAMAGE_STIMULUS”, “GOBP_G2_DNA_DAMAGE_CHECKPOINT” and “GOBP_INTRA_S_DNA_DAMAGE_CHECKPOINT” GSVA scores, and the Wilcoxon rank-sum test p values were 0.0005, 0.0062 and 0.0800, respectively. Furthermore, SRXN1 was upregulated in DU145 cells (resistant to X-ray irradiation compared to PC3 cells) after radiotherapy treatment, and low SRXN1 expression in patients was beneficial to radiotherapy outcomes. The log-rank test p value for PFS was 0.0072. Conclusions Radiotherapy can damage DNA and induce oxidative stress to kill tumour cells. In this study, we found that SRXN1, as an antioxidative stress gene, plays an important role in radiotherapy for prostate cancer treatment, and this gene is also a potential biomarker for predicting the prognosis of patients treated with radiotherapy.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2490Test

الوصول الحر: https://doaj.org/article/5cef5e8e70a244cf82ee0297b766a471Test

المؤلفون: Karthikeyan Murthykumar, Sheeja Varghese, Vijayashree Priyadharsini Jayaseelan

المصدر: Contemporary Clinical Dentistry, Vol 13, Iss 4, Pp 363-368 (2022)

مصطلحات موضوعية: alleles, periodontitis, polymorphism, srxn1 receptor, Dentistry, RK1-715

الوصف: Background: Emerging evidence suggests that oxidative stress forms a key component in the etiopathogenesis of periodontitis. Literature evidence have shown potential antioxidants responsible for combating the pro-oxidants which stress the periodontium, but the peroxiredoxin-sulfiredoxin system is explored very minimally in periodontal disease. Thus, the present study was aimed to evaluate the genetic association of SRXN1 receptor gene polymorphism (rs6053666). Materials and Methods: A total of 100 subjects were recruited for this study, which included 50 Periodontitis patients (Stage II and above based on the criteria of American Association of Periodontology-2018) and 50 periodontally healthy or mild gingivitis. Genomic DNA was extracted from the whole blood collected from the subjects. DNA was amplified using specific primers flanking the BtgI region of the SRXN1 receptor gene. The amplicon was further subjected to genotyping using restriction fragment length using BtgI enzyme. The genotype obtained based on the restriction fragment length polymorphism pattern was recorded and used for statistical analysis. The distribution of genotypes and allele frequencies in the periodontitis and control groups were compared using the Chi-square test. The risk associated with individual alleles or genotypes was calculated as the odds ratio with 95% confidence intervals. Statistical significance in all tests was determined at P < 0.05. Results: The genotype frequency and distributions of SRXN1 receptor BtgI polymorphism did not differ significantly at ꭕ2df (P = 0.557). Our study results showed that homozygous and heterozygous mutant genotypes had no significant difference (CC vs. CT + TT) between the periodontitis patients and control group with a P = 0.4266. The detected frequency of CT (38% vs. 34%) and TT (42% vs. 52%) genotype showed no significant difference between control and test group. There was no significant difference in C allele (39% vs. 31%) and T allele (61% vs. 69%) between the test and control group. Conclusion: The present study denotes that SRXN1 receptor gene polymorphism is not associated with periodontitis in the study group analyzed.

وصف الملف: electronic resource

العلاقة: http://www.contempclindent.org/article.asp?issn=0976-237X;year=2022;volume=13;issue=4;spage=363;epage=368;aulast=MurthykumarTest; https://doaj.org/toc/0976-237XTest; https://doaj.org/toc/0976-2361Test

الوصول الحر: https://doaj.org/article/a6faa745178f40e8b435eeb4b25759fdTest

المؤلفون: Bogdan Ovidiu Popescu, Maria Dobre, Luiza Spiru, Catalina Tudose, Ioana Cracana, Catalina Anca Cucos, Gabriela Niculescu, Gina Manda, Elena Milanesi

المصدر: F1000Research, Vol 11 (2022)

مصطلحات موضوعية: SRXN1, MRI, blood, Cognitive decline, eng, Medicine, Science

الوصف: Introduction: Cognitive decline, correlating with hippocampal atrophy, characterizes several neurodegenerative disorders having a background of low-level chronic inflammation and oxidative stress. Methods: In this cross-sectional study, we examined how cognitive decline and hippocampal subfields volume are associated with the expression of redox and inflammatory genes in peripheral blood. We analyzed 34 individuals with different cognitive scores according to Mini-Mental State Examination, corrected by age and education (adjMMSE). We identified a group presenting cognitive decline (CD) with adjMMSE

وصف الملف: electronic resource

العلاقة: https://f1000research.com/articles/11-114/v2Test; https://doaj.org/toc/2046-1402Test

الوصول الحر: https://doaj.org/article/8dd01394953d4705b8a5c68d5d3cbe40Test

المؤلفون: Jiazhen Zhou, Guanqing Jiang, Enwu Xu, Jiaxin Zhou, Lili Liu, Qiaoyuan Yang

المصدر: Frontiers in Oncology, Vol 11 (2022)

مصطلحات موضوعية: lung cancer, non-small-cell lung cancer, smoking-related gene, KRT6A, SRXN1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: BackgroundLung cancer is the leading cause of cancer-related mortality worldwide. Although cigarette smoking is an established risk factor for lung cancer, few reliable smoking-related biomarkers for non-small-cell lung cancer (NSCLC) are available. An improved understanding of these biomarkers would further the development of new biomarker-targeted therapies and lead to improvements in overall patient survival.MethodsWe performed bioinformatic analysis to screened potential target genes, then quantitative PCR, western, siRNA, CCK-8, flow cytometry, tumorigenicity assays in nude mice were performed to validated the function.ResultsIn this study, we identified 83 smoking-related genes (SRGs) based on an integration analysis of two Gene Expression Omnibus (GEO) datasets, and 27 hub SRGs with potential carcinogenic effects by analyzing a dataset of smokers with NSCLC in The Cancer Genome Atlas (TCGA) database. A survival analysis revealed three genes with potential prognostic value, namely SRXN1, KRT6A and JAKMIP3. A univariate Cox analysis revealed significant associations of elevated SRXN1 and KRT6A expression with prognosis. A receiver operating characteristic (ROC) curve analysis indicated the high diagnostic value of SRXN1 and KRT6A for smoking and cancer. Quantitative PCR and western blotting validated the increased expression of SRXN1 and KRT6A mRNA and protein, respectively, in lung cancer cell lines and NSCLC tissues. In patients with NSCLC, SRXN1 and KRT6A expression was associated with the tumor–node–metastasis (TNM) stage, presence of metastasis, history of smoking and daily smoking consumption. Furthermore, inhibition of SRXN1 or KRT6A suppressed viability and enhanced apoptosis in the A549 human lung carcinoma cell line. Tumorigenicity assays in nude mice confirmed that the siRNA-mediated downregulation of SRXN1 and KRT6A expression inhibited tumor growth in vivo.ConclusionsIn summary, SRXN1 and KRT6A act as oncogenes in NSCLC and might be potential biomarkers of smoking exposure and the early diagnosis and prognosis of NSCLC in smokers, which is vital for lung cancer therapy.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fonc.2021.810301/fullTest; https://doaj.org/toc/2234-943XTest

الوصول الحر: https://doaj.org/article/a3af0aa28c9e4a2d8378e1a2e07fa82bTest

المؤلفون: Bogdan Ovidiu Popescu, Maria Dobre, Luiza Spiru, Catalina Tudose, Ioana Cracana, Catalina Anca Cucos, Gabriela Niculescu, Gina Manda, Elena Milanesi

المصدر: F1000Research, Vol 11 (2022)

مصطلحات موضوعية: SRXN1, MRI, blood, Cognitive decline, eng, Medicine, Science

الوصف: Introduction: Cognitive decline, correlating with hippocampal atrophy, characterizes several neurodegenerative disorders having a background of low-level chronic inflammation and oxidative stress. Methods: In this cross-sectional study, we examined how cognitive decline and hippocampal subfields volume are associated with the expression of redox and inflammatory genes in peripheral blood. We analyzed 34 individuals with different cognitive scores according to Mini-Mental State Examination, corrected by age and education (adjMMSE). We identified a group presenting cognitive decline (CD) with adjMMSE

وصف الملف: electronic resource

العلاقة: https://f1000research.com/articles/11-114/v1Test; https://doaj.org/toc/2046-1402Test

الوصول الحر: https://doaj.org/article/28f1aa4e3dbf43b18874dd664beeff47Test

المؤلفون: Lastres-Becker, I., Morgenstern, C., Demirdögen, B.C., Costa, V.M., Daiber, A., Foresti, R., Motterlini, R.

مصطلحات موضوعية: NRF2, HMOX1 gene, human, nonhuman, NQO1 gene, Nrf2 signaling, oxidative stress, protein function, Review, SRXN1 gene, translational research, TXNRD1 gene, Biomarker, Oxidative stress response, Target genes, Transcription factor, biological marker, glutamate cysteine ligase, glutamate cysteine ligase catalytic subunit, glutamate cysteine ligase modifier subunit, heme oxygenase 1, nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1, reduced nicotinamide adenine dinucleotide phosphate dehydrogenase, sulfiredoxin 1, thioredoxin reductase 1, transcription factor Nrf2, unclassified drug, body fluid, cell protection, GCLC gene

الوصف: The cytoprotective transcription factor NRF2 regulates the expression of several hundred genes in mammalian cells and is a promising therapeutic target in a number of diseases associated with oxidative stress and inflammation. Hence, an ability to monitor basal and inducible NRF2 signalling is vital for mechanistic understanding in translational studies. Due to some caveats related to the direct measurement of NRF2 levels, the modulation of NRF2 activity is typically determined by measuring changes in the expression of one or more of its target genes and/or the associated protein products. However, there is a lack of consensus regarding the most relevant set of these genes/proteins that best represents NRF2 activity across cell types and species. We present the findings of a comprehensive literature search that according to stringent criteria identifies GCLC, GCLM, HMOX1, NQO1, SRXN1 and TXNRD1 as a robust panel of markers that are directly regulated by NRF2 in multiple cell and tissue types. We assess the relevance of these markers in clinically accessible biofluids and highlight future challenges in the development and use of NRF2 biomarkers in humans. © 2024 The Authors ; European Cooperation in Science and Technology, COST: CA20121; Medical Research Council, MRC: MR/X007413/1

العلاقة: Redox Biology; DiÄŸer; https://doi.org/10.1016/j.redox.2024.103134Test; https://hdl.handle.net/20.500.11851/11559Test; 72; WOS:001233628200001; 2-s2.0-85190738421

الإتاحة: https://doi.org/20.500.11851/1155910.1016/j.redox.2024.103134Test
https://hdl.handle.net/20.500.11851/11559Test

المؤلفون: Erika Moro, Johannes P Schimming, José V. Castell, Bas ter Braak, Laia Tolosa, Barbara M.A. van Vugt-Lussenburg, Bob van der Water, Teresa Martínez-Sena, Miguel A. Miranda, Sylvia Escher

المساهمون: Publica

المصدر: Digital.CSIC. Repositorio Institucional del CSIC
instname
Archives of Toxicology, 95(6), 2109-2121. Springer Science and Business Media LLC
ARCHIVES OF TOXICOLOGY
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
Archives of Toxicology

مصطلحات موضوعية: Redox-cycling phenols, Plastic seals, 0301 basic medicine, Cytotox CALUX reporter gene assay, Health, Toxicology and Mutagenesis, Diffusion, HepG2 BAC-GFP SRXN1 assay, 010501 environmental sciences, Toxicology, 01 natural sciences, Gas Chromatography-Mass Spectrometry, 03 medical and health sciences, chemistry.chemical_compound, Phenols, Cross-contamination of culture wells, Cell Line, Tumor, Humans, Incubation, 0105 earth and related environmental sciences, Nrf2 CALUX reporter gene assay, Hepatotoxicity, Reproducibility of Results, Hep G2 Cells, General Medicine, In vitro toxicity, In vitro, High-Throughput Screening Assays, Hydroquinones, Quinone, In Vitro Systems, 030104 developmental biology, chemistry, Environmental chemistry, Toxicity, Degradation (geology), Oxidation-Reduction, Redox cycling, Toxicity of phenols, High-content imaging

الوصف: Phenols are regarded as highly toxic chemicals. Their effects are difficult to study in in vitro systems because of their ambiguous fate (degradation, auto-oxidation and volatility). In the course of in vitro studies of a series of redox-cycling phenols, we found evidences of cross-contamination in several in vitro high-throughput test systems, in particular by trimethylbenzene-1, 4-diol/trimethylhydroquinone (TMHQ) and 2,6-di-tertbutyl-4-ethylphenol (DTBEP), and investigated in detail the physicochemical basis for such phenomenon and how to prevent it. TMHQ has fast degradation kinetics followed by significant diffusion rates of the resulting quinone to adjacent wells, other degradation products being able to air-diffuse as well. DTBEP showed lower degradation kinetics, but a higher diffusion rate. In both cases the in vitro toxicity was underestimated because of a decrease in concentration, in addition to cross-contamination to neighbouring wells. We identified four degradation products for TMHQ and five for DTBEP indicating that the current effects measured on cells are not only attributable to the parent phenolic compound. To overcome these drawbacks, we investigated in detail the physicochemical changes occurring in the course of the incubation and made use of gas-permeable and non-permeable plastic seals to prevent it. Diffusion was greatly prevented by the use of both plastic seals, as revealed by GC–MS analysis. Gas non-permeable plastic seals, reduced to a minimum compounds diffusion as well oxidation and did not affect the biological performance of cultured cells. Hence, no toxicological cross-contamination was observed in neighbouring wells, thus allowing a more reliable in vitro assessment of phenol-induced toxicity.
The authors wish to acknowledge the support of the European Union’s Horizon 2020 research and innovation 493 program under Grant Agreement No 681002 (EU-ToxRisk). We are indebted to CIBEREHD (ISCIII), for supporting our research program on hepatotoxicity of xenobiotics. L.T. was supported by the Miguel 494 Servet I Program financed by the Institute of Health Carlos III (Plan Estatal de I+D+i 2013-2016) 495 and co-financed by the European Regional Development Fund "A way to achieve Europe" (FEDER) 496 through grant CP16/00097. TMS acknowledges her personal predoctoral grant (FI18/00260, 497 ISCIII, Spain).

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::96b272012eddeb7cdefeccbea6af2290Test
https://doi.org/10.1007/s00204-021-03036-wTest

المؤلفون: Huimin Lan, Hui Luo, Xiaopeng Hong, Chaoming Mei, Hailing Yu, Wenkai Zhang, Qianqian Zhang, Hong Shan, Ting Yu, Pengfei Pang, Xiufang Lv, Quanyong Huang

المصدر: Journal of Cellular and Molecular Medicine

مصطلحات موضوعية: Male, 0301 basic medicine, Lung Neoplasms, medicine.disease_cause, Metastasis, Mice, 0302 clinical medicine, Cell Movement, BTG2, Oxidoreductases Acting on Sulfur Group Donors, RNA, Neoplasm, Neoplasm Metastasis, RNA, Small Interfering, Tumor Stem Cell Assay, Mice, Inbred BALB C, Gene knockdown, Liver Neoplasms, Cell migration, hepatocellular carcinoma, Transfection, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Cell Transformation, Neoplastic, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Molecular Medicine, RNA Interference, Original Article, Carcinoma, Hepatocellular, Epithelial-Mesenchymal Transition, Mice, Nude, Biology, Immediate-Early Proteins, 03 medical and health sciences, Cell Line, Tumor, medicine, Animals, Humans, metastasis, Neoplasm Invasiveness, RNA, Messenger, neoplasms, Cell growth, Tumor Suppressor Proteins, Original Articles, Cell Biology, medicine.disease, digestive system diseases, 030104 developmental biology, SRXN1, Cancer research, Reactive Oxygen Species, Carcinogenesis, Neoplasm Transplantation, Transcription Factors

الوصف: Sulfiredoxin 1 (SRXN1) is a pivotal regulator of the antioxidant response in eukaryotic cells. However, the role of SRXN1 in hepatocellular carcinoma (HCC) is far from clear. The present study aims to elucidate whether SRXN1 participates in tumorigenesis and metastasis of HCC and to determine the molecular mechanisms. We found that SRXN1 expression was up‐regulated in HCC tissue samples and correlated with poor prognosis in HCC patients. We also observed that SRXN1 knockdown by transient siRNA transfection inhibited HCC cell proliferation, migration and invasion. Overexpression of SRXN1 increased HCC cell migration and invasion. B‐cell translocation gene 2 (BTG2) was identified as a downstream target of SRXN1. Mechanistic studies revealed that SRXN1‐depleted reactive oxygen species (ROS) modulated migration and invasion of HCC cells. In addition, the ROS/p65/BTG2 signalling hub was found to regulate the epithelial‐mesenchymal transition (EMT), which mediates the pro‐metastasis role of SRXN1 in HCC cells. In vivo experiments showed SRXN1 promotes HCC tumour growth and metastasis in mouse subcutaneous xenograft and metastasis models. Collectively, our results revealed a novel pro‐tumorigenic and pro‐metastatic function of SRXN1 in HCC. These findings demonstrate a rationale to exploit SRXN1 as a therapeutic target effectively preventing metastasis of HCC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c6d403f486fe05d7a6a59e72d43321b2Test
https://doi.org/10.1111/jcmm.15693Test

المؤلفون: Bischoff, L.J.M.

المساهمون: Water, B. van de, Noort, D., Langenberg, J.P., Irth, H., Bouwstra, J.A., Jennings, P., Lange, E.C.M. de, Vrieling, H., Leiden University

المصدر: None

مصطلحات موضوعية: Repeated exposure, HepG2, Srxn1, MicroRNA, Biomarker, respiratory system, environment and public health, Nrf2, Phenolic compounds

الوصف: The focus of the described research in this thesis is on the oxidative stress response (Nrf2 pathway). The aim of the research presented in this thesis is to obtain more information concerning microRNAs which are involved in the Nrf2 pathway, to determine and evaluate the application of microRNAs for the construction of novel mechanistic biomarkers. Furthermore, we aimed to obtain a better understandingwith respect to the dynamics of the Nrf2 pathway to repeated xenobiotic exposure.To investigate the effect of overexpression of microRNAs on the Nrf2 pathway response in general and in combination with chemical exposure, a microRNA mimic screen was performed. In this screen overexpression of microRNAs was induced by using synthetic microRNA mimics. Since repeated exposure may drive adaptation programs and may lead to different responses between single and repeated exposures. The effect of a second exposure on the dynamics of the Nrf2 pathway activation was conducted. Final, results of a study are shown where a panel of structurally different phenolic compounds were used to demonstrate the proof-of-concept that Nrf2 pathway reporters can successfully be applied as biomarkers to characterize the specific pro-oxidant responses of chemicals.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::6f4bd25fc61bc3629b54d3337112cb8fTest
https://hdl.handle.net/1887/3249612Test