Antioxidants & redox signaling最新文献

{"title":"Pathomechanistic Synergy Between Particulate Matter and Traffic Noise-Induced Cardiovascular Damage and the Classical Risk Factor Hypertension.","authors":"Marin Kuntic, Omar Hahad, Sadeer Al-Kindi, Matthias Oelze, Jos Lelieveld, Andreas Daiber, Thomas Münzel","doi":"10.1089/ars.2024.0659","DOIUrl":"10.1089/ars.2024.0659","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CARD11-BCL10-MALT1 Complex-Dependent MALT1 Activation Facilitates Myocardial Oxidative Stress in Doxorubicin-Treated Mice via Enhancing k48-Linked Ubiquitination of Nrf2.","authors":"Li-Qun Lu, Ming-Rui Li, Xu-Yan Liu, Dan Peng, Hong-Rui Liu, Xiao-Jie Zhang, Xiu-Ju Luo, Jun Peng","doi":"10.1089/ars.2023.0543","DOIUrl":"10.1089/ars.2023.0543","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) contributes to doxorubicin (DOX)-induced myocardial oxidative stress, and inhibition of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) increased Nrf2 protein level in rat heart suffering ischemia/reperfusion, indicating a connection between MALT1 and Nrf2. This study aims to explore the role of MALT1 in DOX-induced myocardial oxidative stress and the underlying mechanisms. <b><i>Results:</i></b> The mice received a single injection of DOX (15 mg/kg, i.p.) to induce myocardial oxidative stress, evidenced by increases in the levels of reactive oxidative species as well as decreases in the activities of antioxidative enzymes, concomitant with a downregulation of Nrf2; these phenomena were reversed by MALT1 inhibitor. Similar phenomena were observed in DOX-induced oxidative stress in cardiomyocytes. Mechanistically, knockdown or inhibition of MALT1 notably attenuated the interaction between Nrf2 and MALT1 and decreased the k48-linked ubiquitination of Nrf2. Furthermore, inhibition or knockdown of calcium/calmodulin-dependent protein kinase II (CaMKII-δ) reduced the phosphorylation of caspase recruitment domain-containing protein 11 (CARD11), subsequently disrupted the assembly of CARD11, B cell lymphoma 10 (BCL10), and MALT1 (CBM) complex, and reduced the MALT1-dependent k48-linked ubiquitination of Nrf2 in DOX-treated mice or cardiomyocytes. <b><i>Innovation and Conclusion:</i></b> The E3 ubiquitin ligase function of MALT1 accounts for the downregulation of Nrf2 and aggravation of myocardial oxidative stress in DOX-treated mice, and CaMKII-δ-dependent phosphorylation of CARD11 triggered the assembly of CBM complex and the subsequent activation of MALT1.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Scavenger Receptor Class B Type I Deficiency Induces Iron Overload and Ferroptosis in Renal Tubular Epithelial Cells <i>via</i> Hypoxia-Inducible Factor-1α/Transferrin Receptor 1 Signaling Pathway.","authors":"LiJiao Yang, Qing Liu, QianYu Lu, Jing-Jie Xiao, An-Yao Fu, Shan Wang, LiHua Ni, Jun-Wei Hu, Hong Yu, XiaoYan Wu, Bai-Fang Zhang","doi":"10.1089/ars.2023.0380","DOIUrl":"10.1089/ars.2023.0380","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Scavenger receptor class B type I (SRBI) promotes cell cholesterol efflux and the clearance of plasma cholesterol. Thus, <i>SRBI</i> deficiency causes abnormal cholesterol metabolism and hyperlipidemia. Studies have suggested that ferroptosis is involved in lipotoxicity; however, whether <i>SRBI</i> deficiency could induce ferroptosis remains to be investigated. <b><i>Results:</i></b> We knocked down or knocked out SRBI in renal HK-2 cells and C57BL/6 mice to determine the expression levels of ferroptosis-related regulators. Our results demonstrated that <i>SRBI</i> deficiency upregulates transferrin receptor 1 (TFR1) expression and downregulates ferroportin expression, which induces iron overload and subsequent ferroptosis in renal tubular epithelial cells. TFR1 is known to be regulated by hypoxia-inducible factor-1α (HIF-1α). Next, we investigated whether <i>SRBI</i> deletion affected HIF-1α. SRBI deletion upregulated the mRNA and protein expression of HIF-1α, and promoted its translocation to the nucleus. To determine whether HIF-1α plays a key role in <i>SRBI</i>-deficiency-induced ferroptosis, we used HIF-1α inhibitor and siHIF-1α in HK-2 cells, and found that downregulation of HIF-1α prevented SRBI-silencing-induced TFR1 upregulation and iron overload, and eventually reduced ferroptosis. The underlying mechanism of HIF-1α activation was explored next, and the results showed that SRBI knockout or knockdown may upregulate the expression of HIF-1α, and promote HIF-1α translocation from the cytoplasm into the nucleus <i>via</i> the PKC-β/NF-κB signaling pathway. <b><i>Innovation and Conclusion:</i></b> Our study showed, for the first time, that <i>SRBI</i> deficiency induces iron overload and subsequent ferroptosis <i>via</i> the HIF-1α/TFR1 pathway.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"56-73"},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal Administration of Acetaminophen Affects Meiosis Through its Metabolite NAPQI Targeting SIRT7 in Fetal Oocytes.","authors":"Fangfei Liu, Junlin He, Xuemei Chen, Ronglu Liu, Fangfang Li, Yanqing Geng, Yuhan Dai, Yan Zhang, Yingxiong Wang, Xinyi Mu","doi":"10.1089/ars.2023.0270","DOIUrl":"10.1089/ars.2023.0270","url":null,"abstract":"<p><p><b><i>Aim:</i></b> Acetaminophen (APAP) is clinically recommended as analgesic and antipyretic among pregnant women. However, accumulating laboratory evidence shows that the use of APAP during pregnancy may alter fetal development. Since fetal stage is a susceptible window for early oogenesis, we aim to assess the potential effects of maternal administration of APAP on fetal oocytes. <b><i>Results:</i></b> Pregnant mice at 14.5 dpc (days post-coitus) were orally administered with APAP (50 and 150mg/kg.bw/day) for 3 days; meanwhile, 14.5 dpc ovaries were collected and cultured with APAP or its metabolite N-acetyl-p-benzoquinone imine (NAPQI; 5 and 15 μ<i>M</i>) for 3 days. It showed that APAP caused meiotic aberrations in fetal oocytes through its metabolite NAPQI, including meiotic prophase I (MPI) progression delay and homologous recombination defects. Co-treatment with nicotinamide (NAM) or nicotinamide riboside chloride (NRC), nicotinamide adenine dinucleotide (NAD⁺) supplements, efficiently restored the MPI arrest, whereas the addition of the inhibitor of sirtuin 7 (SIRT7) invalidated the effect of the NAD⁺ supplement. In addition, RNA sequencing revealed distorted transcriptomes of fetal ovaries treated with NAPQI. Furthermore, the fecundity of female offspring was affected, exhibiting delayed primordial folliculogenesis and puberty onset, reduced levels of ovarian hormones, and impaired developmental competence of MII oocytes. <b><i>Innovation:</i></b> These findings provide the first known demonstration that NAPQI, converted from maternal administration of APAP, disturbs meiotic process of fetal oocytes and further impairs female fecundity in adulthood. The concomitant oral dosing with NAM further supports the benefits of NAD⁺ supplements on oogenesis. <b><i>Conclusion:</i></b> Short-term administration of APAP to pregnant mouse caused meiotic aberrations in fetal oocytes by its metabolite NAPQI, whereas co-treatment with NAD⁺ supplement efficiently relieves the adverse effects by interacting with SIRT7.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"93-109"},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-Analysis of Antioxidant Mutants Reveals Common Alarm Signals for Shaping Abiotic Stress-Induced Transcriptome in Plants.","authors":"Shefali Mishra, Thumballi Ramabhatta Ganapathi, Girdhar Kumar Pandey, Christine Helen Foyer, Ashish Kumar Srivastava","doi":"10.1089/ars.2023.0361","DOIUrl":"10.1089/ars.2023.0361","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"42-55"},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10402523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel lncRNA FUAT1/TNS4 Axis Confers Chemoresistance by Suppressing Reactive Oxygen Species-Mediated Apoptosis in Gastric Cancer.","authors":"Mingliang Liu, Hehe Li, Xiaoling Li, Boyu Pan, Jian Zhang, Ya Pan, Miaomiao Shen, Liren Liu","doi":"10.1089/ars.2023.0298","DOIUrl":"10.1089/ars.2023.0298","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"24-41"},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10144961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isopentyl-Deoxynboquinone Induces Mitochondrial Dysfunction and G2/M Phase Cell Cycle Arrest to Selectively Kill <i>NQO1</i>-Positive Pancreatic Cancer Cells.","authors":"Lingxiang Jiang, Yingchun Liu, Soumya Tumbath, Matthew W Boudreau, Lindsay E Chatkewitz, Jiangwei Wang, Xiaolin Su, Kashif Rafiq Zahid, Katherine Li, Yaomin Chen, Kai Yang, Paul J Hergenrother, Xiumei Huang","doi":"10.1089/ars.2022.0224","DOIUrl":"10.1089/ars.2022.0224","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Pancreatic cancer is among the top five leading causes of cancer-related deaths worldwide, with poor overall survival rates. Current therapies for pancreatic cancer lack tumor specificity, resulting in harmful effects on normal tissues. Therefore, developing tumor-specific agents for the treatment of pancreatic cancer is critical. NAD(P)H:quinone oxidoreductase 1 (NQO1), highly expressed in pancreatic cancers but not in associated normal tissues, makes NQO1 bioactivatable drugs a potential therapy for selectively killing <i>NQO1</i>-positive cancer cells. Our previous studies have revealed that the novel NQO1 bioactivatable drug deoxynyboquinone (DNQ) is 10-fold more potent than the prototypic NQO1 bioactivatable drug β-lapachone in killing of <i>NQO1</i>-positive cancer cells. However, DNQ treatment results in high-grade methemoglobinemia, a significant side effect that limits clinical development. <b><i>Results:</i></b> Here, we report for the first time on a DNQ derivative, isopentyl-deoxynboquinone (IP-DNQ), which selectively kills pancreatic ductal adenocarcinoma (PDAC) cells in an NQO1-dependent manner with equal potency to the parent DNQ. IP-DNQ evokes massive reactive oxygen species (ROS) production and oxidative DNA lesions that result in poly(ADP-ribose)polymerase-1 (PARP1) hyperactivation, mitochondrial catastrophe, and G2/M phase cell cycle arrest, leading to apoptotic and necrotic programmed cell death. Importantly, IP-DNQ treatment causes only mild methemoglobinemia <i>in vivo</i>, with a threefold improvement in the maximum tolerated dose (MTD) compared with DNQ, while it significantly suppresses tumor growth and extends the life span of mice in subcutaneous and orthotopic pancreatic cancer xenograft models. <b><i>Innovation and Conclusion:</i></b> Our study demonstrates that IP-DNQ is a promising therapy for <i>NQO1</i>-positive pancreatic cancers and may enhance the efficacy of other anticancer drugs. IP-DNQ represents a novel approach to treating pancreatic cancer with the potential to improve patient outcomes.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"74-92"},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89716720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioengineered MSC^{<i>GFPCxcr2-Mmp13</i>} Transplantation Alleviates Hepatic Fibrosis by Regulating Mammalian Target of Rapamycin Signaling.","authors":"Shilpa Chawla, Subholakshmi Choudhury, Amitava Das","doi":"10.1089/ars.2023.0390","DOIUrl":"10.1089/ars.2023.0390","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Hepatic fibrosis is the pathological change during chronic liver diseases (CLD) that turns into cirrhosis if not reversed timely. Allogenic mesenchymal stem cell (MSC) therapy is an alternative to liver transplantation for CLD. However, poor engraftment of the transplanted MSCs limits their therapeutic efficacy. MSCs express chemokine receptors that regulate their physiology. We observed several-fold increased expressions of <i>Cxcl3</i> and decreased expression of <i>Mmp13</i> in the fibrotic liver. Therefore, we bioengineered MSCs with stable overexpression of <i>Cxcr2</i> (CXCL3-cognate receptor) and <i>Mmp13,</i> collagenase (MSC^{<i>GFPCxcr2-Mmp13</i>}). <b><i>Results:</i></b> The CXCL3/CXCR2 axis significantly increased migration through the activation of AKT/ERK/mTOR signaling. These bioengineered MSCs transdifferentiated into hepatocyte-like cells (MSC^{<i>GFPCxcr2-Mmp13</i>}-HLCs) that endured the drug-/hepatotoxicant-induced toxicity by significantly increasing the antioxidants-<i>Nrf2</i> and <i>Sod2,</i> while decreasing the apoptosis-<i>Cyt C, Casp3, Casp9</i>, and drug-metabolizing enzyme-<i>Cyp1A1, Cyp1A2, Cyp2E1</i> markers. Therapeutic transplantation of MSC^{<i>GFPCxcr2-Mmp13</i>} abrogated AAP-/CCl₄-induced hepatic fibrosis in mice by CXCR2-mediated targeted engraftment and MMP-13-mediated reduction in collagen. Mechanistically, induction of CXCL3/CXCR2 axis-activated mTOR-p70S6K signaling led to increased targeted engraftment and modulation of the oxidative stress by increasing the expression and activity of nuclear Nrf2 and SOD2 expression in the regenerated hepatic tissues. A marked change in the fate of transplanted MSC^{<i>GFPCxcr2-Mmp13</i>} toward hepatocyte lineage demonstrated by co-immunostaining of GFP/HNF4α along with reduced COL1α1 facilitated the regeneration of the fibrotic liver. <b><i>Innovation and Conclusions:</i></b> Our study suggests the therapeutic role of allogenic <i>Cxcr2/Mmp13-</i>bioengineered MSC transplantation decreases the hepatic oxidative stress as an effective translational therapy for hepatic fibrosis mitigation-mediated liver regeneration.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"110-137"},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139110685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathological Impact of Redox Post-Translational Modifications.","authors":"Charbel Chahla, Hervé Kovacic, Lotfi Ferhat, Ludovic Leloup","doi":"10.1089/ars.2023.0252","DOIUrl":"10.1089/ars.2023.0252","url":null,"abstract":"<p><p>Oxidative stress is involved in the development of several pathologies. The different reactive oxygen species (ROS) produced during oxidative stress are at the origin of redox post-translational modifications (PTMs) on proteins and impact nucleic acids and lipids. This review provides an overview of recent data on cysteine and methionine oxidation and protein carbonylation following oxidative stress in a pathological context. Oxidation, like nitration, is a selective process and not all proteins are impacted. It depends on multiple factors, including amino acid environment, accessibility, and physical and chemical properties, as well as protein structures. Thiols can undergo reversible oxidations and others that are irreversible. On the contrary, carbonylation represents irreversible PTM. To date, hundreds of proteins were shown to be modified by ROS and reactive nitrogen species (RNS). We reviewed recent advances in the impact of redox-induced PTMs on protein functions and activity, as well as its involvement in disease development or treatment. These data show a complex situation of the involvement of redox PTM on the function of targeted proteins. Many proteins can have their activity decreased by the oxidation of cysteine thiols or methionine S-methyl thioethers, while for other proteins, this oxidation will be activating. This complexity of redox PTM regulation suggests that a global antioxidant therapeutic approach, as often proposed, is unlikely to be effective. However, the specificity of the effect obtained by targeting a cysteine or methionine residue to be able to inactivate or activate a particular protein represents a major interest if it is possible to consider this targeting from a therapeutic point of view with our current pharmacological tools. <i>Antioxid. Redox Signal.</i> 41, 152-180.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"152-180"},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of Hypoxia Inducible Factor-1 Alpha-Mediated DNA Methylation Enzymes (DNMT3a and TET2) Under Hypoxic Conditions Regulates S100A6 Transcription to Promote Lung Cancer Cell Growth and Metastasis.","authors":"Tengfei Wang, Genbao Zhu, Bo Wang, Mengxue Hu, Chen Gong, Kemeng Tan, La Jiang, Xiaohong Zhu, Yuliu Geng, Lili Li","doi":"10.1089/ars.2023.0397","DOIUrl":"10.1089/ars.2023.0397","url":null,"abstract":"<p><p><b><i>Aims:</i></b> This research was aimed at investigating the effects of hypoxia inducible factor-1 alpha (HIF-1α)-mediated DNA methylation enzymes (ten-eleven translocase-2 [TET2] and DNA methyltransferase-3a [DNMT3a]) under hypoxic conditions on S100A6 transcription, thereby promoting the growth and metastasis of lung cancer cells. <b><i>Methods:</i></b> The expression of HIF-1α or S100A6 in lung cancer cells was interfered with under normoxic and hypoxic conditions, and the cell proliferative, migratory, and invasive properties were assessed. The mechanism of HIF-1α-regulated TET2 and DNMT3 effects on S100A6 transcription under hypoxic conditions was further investigated. <b><i>Results:</i></b> Functionally, S100A6 over-expression promoted lung cancer cell proliferation and metastasis. S100A6 over-expression reversed the inhibitory effects of HIF-1α interference on the proliferation and metastasis of lung cancer cells. S100A6 was induced to express in an HIF-1α-dependent manner under hypoxic conditions, and silencing S100A6 or HIF-1α suppressed lung cancer cell proliferation and metastasis under hypoxic conditions. Further, The Cancer Genome Atlas-lung adenocarcinoma database analysis revealed that S100A6 mRNA levels had a negative correlation with methylation levels. Mechanistically, CpG hypomethylation status in the S100A6 promoter hypoxia response element had an association with HIF-1α induction. TET2 was enriched in S100A6 promoter region of lung cancer cells under hypoxic conditions, whereas DNMT3a enrichment was reduced in S100A6 promoter region. HIF-1α-mediated S100A6 activation was linked to DNMT3a-associated epigenetic inactivation and TET2 activation. <b><i>Innovation:</i></b> The activation of HIF-1α-mediated DNA methylation enzymes under hypoxic conditions regulated S100A6 transcription, thereby promoting lung cancer cell growth and metastasis. <b><i>Conclusion:</i></b> In lung cancer progression, hypoxia-induced factor HIF-1α combined with DNA methylation modifications co-regulates S100A6 transcriptional activation and promotes lung cancer cell growth and metastasis.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"138-151"},"PeriodicalIF":5.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139650178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}