Redox Biology最新文献

{"title":"Mesenchymal stem cell-derived extracellular vesicles attenuate ferroptosis in aged hepatic ischemia/reperfusion injury by transferring miR-1275","authors":"Yihang Gong ,&nbsp;Qiang You ,&nbsp;Xiaofeng Yuan ,&nbsp;Fanxin Zeng ,&nbsp;Feng Zhang ,&nbsp;Jiaqi Xiao ,&nbsp;Haitian Chen ,&nbsp;Yasong Liu ,&nbsp;Tingting Wang ,&nbsp;Xijing Yan ,&nbsp;Wenjie Chen ,&nbsp;Yingcai Zhang ,&nbsp;Qi Zhang ,&nbsp;Jia Yao ,&nbsp;Jiebin Zhang ,&nbsp;Rong Li ,&nbsp;Jun Zheng","doi":"10.1016/j.redox.2025.103556","DOIUrl":"10.1016/j.redox.2025.103556","url":null,"abstract":"<div><div>With an aging global population, the proportion of aged donor livers in graft pools is steadily increasing. Compared to young livers, aged livers exhibit heightened susceptibility to hepatic ischemia/reperfusion injury (HIRI), which significantly limits their utilisation in liver transplantation (LT) and exacerbates organ shortages. Our previous study demonstrated that ferroptosis is a pivotal trigger for HIRI vulnerability in aged livers. However, effective clinical strategies for the inhibition of ferroptosis remain elusive. Utilizing an aged mouse HIRI model, primary hepatocytes, and human liver organoids, this study provides hitherto undocumented evidence that mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) effectively alleviate HIRI in aged livers by inhibiting ferroptosis. Mechanistically, miR-1275, which was significantly enriched within MSC-EVs, was transferred to hepatocytes. Subsequently, miR-1275 downregulated the expression of SLC39A14, a crucial iron transporter that is upregulated in aged livers and plays a pivotal role in promoting ferroptosis. Furthermore, we found a negative correlation between SLC39A14 levels and prognosis of aged donor liver recipients using clinical LT samples. Silencing miR-1275 in MSC-EVs or modulating SLC39A14 levels in aged livers reversed MSC-EV-mediated mitigation of ferroptosis. Collectively, these findings revealed the novel therapeutic potential of MSC-EVs in attenuating aged HIRI, suggesting a promising treatment for improving prognosis and preventing serious complications in recipients of aged liver grafts during LT.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103556"},"PeriodicalIF":10.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Aspirin promotes RSL3-induced ferroptosis by suppressing mTOR/SREBP-1/SCD1-mediated lipogenesis in PIK3CA-mutatnt colorectal cancer” [Redox Biol. 55 (2022) 102426]","authors":"Hao Chen ,&nbsp;Qinqin Qi ,&nbsp;Nan Wu ,&nbsp;Ying Wang ,&nbsp;Qian Feng ,&nbsp;Rong Jin ,&nbsp;Lei Jiang","doi":"10.1016/j.redox.2025.103533","DOIUrl":"10.1016/j.redox.2025.103533","url":null,"abstract":"","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"80 ","pages":"Article 103533"},"PeriodicalIF":10.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper in melanoma: At the crossroad of protumorigenic and anticancer roles","authors":"Natalia Chrzan,&nbsp;Mariusz L. Hartman","doi":"10.1016/j.redox.2025.103552","DOIUrl":"10.1016/j.redox.2025.103552","url":null,"abstract":"<div><div>Copper is an essential micronutrient that is a cofactor for various enzymes involved in multiple cellular processes. Melanoma patients have high serum copper levels, and elevated copper concentrations are found in melanoma tumors. Copper influences the activity of several melanoma-related proteins involved in cell survival, proliferation, pigmentation, angiogenesis, and metastasis. Targeting these processes with copper chelators has shown efficacy in reducing tumor growth and overcoming drug resistance. In contrast, excessive copper can also have detrimental effects when imported into melanoma cells. Multiple distinct cellular effects of copper overload, including the induction of different types of cell death, have been reported. Cuproptosis, a novel type of copper-dependent cell death, has been recently described and is associated with the metabolic phenotype. Melanoma cells can switch between glycolysis and oxidative phosphorylation, which are crucial for tumor growth and drug resistance. In this respect, metabolic plasticity might be exploited for the use of copper-delivery strategies, including repurposing of disulfiram, which is approved for the treatment of noncancer patients. In addition, the development of nanomedicines can improve the targeted delivery of copper to melanoma cells and enable the use of these drugs alone or in combination as copper has been shown to complement targeted therapy and immunotherapy in melanoma cells. However, further research is needed to explore the specific mechanisms of both copper restriction and excess copper-induced processes and determine effective biomarkers for predicting treatment sensitivity in melanoma patients. In this review, we discuss the dual role of copper in melanoma biology.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103552"},"PeriodicalIF":10.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone lactylation drives liver cancer metastasis by facilitating NSF1-mediated ferroptosis resistance after microwave ablation","authors":"Jiayan Huang ,&nbsp;Huijing Xie ,&nbsp;Ju Li ,&nbsp;Xiaotong Huang ,&nbsp;Yunshi Cai ,&nbsp;Rui Yang ,&nbsp;Dongmei Yang ,&nbsp;Wuyongga Bao ,&nbsp;Yongjie Zhou ,&nbsp;Tao Li ,&nbsp;Qiang Lu","doi":"10.1016/j.redox.2025.103553","DOIUrl":"10.1016/j.redox.2025.103553","url":null,"abstract":"<div><div>Insufficient microwave ablation (IMWA) is linked to aggressive hepatocellular carcinoma (HCC) progression. An increase in lactate levels after sublethal heat stress (HS) has been confirmed in HCC. However, the role of lactate-related histone lactylation in the progression of HCC caused by sublethal HS remains unclear. Here, we found that the metastatic potential of HCC increased in a lactate-dependent manner after IMWA. Moreover, sublethal HS triggered an increase in H3K18la modification, as validated in a cell-derived xenograft mouse model and human HCC samples. By performing an integrated analysis of proteomic and transcriptomic profiles, we revealed that HCC cells exhibited increased intracellular iron ion homeostasis and developed resistance to platinum-based drugs after exposure to sublethal HS. We subsequently integrated proteomic and transcriptomic data with H3K18la-specific chromatin immunoprecipitation (ChIP) sequencing to identify candidate genes involved in sublethal heat treatment-induced HCC cell metastasis. Mechanically, an increase in H3K18la modification enhanced the transcriptional activity of NFS1 cysteine desulfurase (NFS1), a key player in iron‒sulfur cluster biosynthesis, thereby reducing the susceptibility of HCC to ferroptosis after IMWA. Knocking down NFS1 diminished the metastatic potential of sublethally heat-treated HCC cells. Additionally, NFS1 deficiency exhibited a synergistic effect with oxaliplatin, leading to the significant inhibition of the metastatic capability of HCC cells both in vitro and in vivo, regardless of sublethal HS treatment. In conclusion, our study revealed the oncogenic role of histone lactylation in HCC after IMVA. We also bridged histone lactylation with ferroptosis, providing novel therapeutic targets for HCC following microwave ablation, particularly when combined with oxaliplatin-based chemotherapy.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103553"},"PeriodicalIF":10.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-tissue metabolomics reveal mtDNA- and diet-specific metabolite profiles in a mouse model of cardiometabolic disease","authors":"Abhishek Shastry ,&nbsp;Mia S. Wilkinson ,&nbsp;Dalia M. Miller ,&nbsp;Michelle Kuriakose ,&nbsp;Jennifer L.M.H. Veeneman ,&nbsp;Matthew Ryan Smith ,&nbsp;Charles C.T. Hindmarch ,&nbsp;Kimberly J. Dunham-Snary","doi":"10.1016/j.redox.2025.103541","DOIUrl":"10.1016/j.redox.2025.103541","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Rationale&lt;/h3&gt;&lt;div&gt;Excess consumption of sugar- and fat-rich foods has heightened the prevalence of cardiometabolic disease, which remains a driver of cardiovascular disease- and type II diabetes-related mortality globally. Skeletal muscle insulin resistance is an early feature of cardiometabolic disease and is a precursor to diabetes. Insulin resistance risk varies with self-reported race, whereby African-Americans have a greater risk of diabetes development relative to their White counterparts. Self-reported race is strongly associated with mitochondrial DNA (mtDNA) haplogroups, and previous reports have noted marked differences in bioenergetic and metabolic parameters in cells belonging to distinct mtDNA haplogroups, but the mechanism of these associations remains unknown. Additionally, distinguishing nuclear DNA (nDNA) and mtDNA contributions to cardiometabolic disease remains challenging in humans. The Mitochondrial-Nuclear eXchange (MNX) mouse model enables &lt;em&gt;in vivo&lt;/em&gt; preclinical investigation of the role of mtDNA in cardiometabolic disease development, and has been implemented in studies of insulin resistance, fatty liver disease, and obesity in previous reports.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Six-week-old male C57&lt;sup&gt;nDNA&lt;/sup&gt;:C57&lt;sup&gt;mtDNA&lt;/sup&gt; and C3H&lt;sup&gt;nDNA&lt;/sup&gt;:C3H&lt;sup&gt;mtDNA&lt;/sup&gt; wild-type mice, and C57&lt;sup&gt;nDNA&lt;/sup&gt;:C3H&lt;sup&gt;mtDNA&lt;/sup&gt; and C3H&lt;sup&gt;nDNA&lt;/sup&gt;:C57&lt;sup&gt;mtDNA&lt;/sup&gt; MNX mice, were fed sucrose-matched high-fat (45% kcal fat) or control diet (10% kcal fat) until 12 weeks of age (n = 5/group). Mice were weighed weekly and total body fat was collected at euthanasia. Gastrocnemius skeletal muscle and plasma metabolomes were characterized using untargeted dual-chromatography mass spectrometry; both hydrophilic interaction liquid chromatography (HILIC) and C18 columns were used, in positive- and negative-ion modes, respectively.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Comparative analyses between nDNA-matched wild-type and MNX strains demonstrated significantly increased body fat percentage in mice possessing C57&lt;sup&gt;mtDNA&lt;/sup&gt; regardless of nDNA background. High-fat diet in mice possessing C57&lt;sup&gt;mtDNA&lt;/sup&gt; was associated with differential abundance of phosphatidylcholines, lysophosphatidylcholines, phosphatidylethanolamines, and glucose. Conversely, high-fat diet in mice possessing C3H&lt;sup&gt;mtDNA&lt;/sup&gt; was associated with differential abundance of phosphatidylcholines, cardiolipins, and alanine. Glycerophospholipid metabolism and beta-alanine signaling pathways were enriched in skeletal muscle and plasma, indicating mtDNA-directed priming of mitochondria towards oxidative stress and increased fatty acid oxidation in C57&lt;sup&gt;nDNA&lt;/sup&gt;:C57&lt;sup&gt;mtDNA&lt;/sup&gt; wild-type and C3H&lt;sup&gt;nDNA&lt;/sup&gt;:C57&lt;sup&gt;mtDNA&lt;/sup&gt; MNX mice, relative to their nDNA-matched counterparts. In mtDNA-matched mice, C57&lt;sup&gt;mtDNA&lt;/sup&gt; was associated with metabolite co-expression related to the pentose phosphate pathway and sugar-re","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103541"},"PeriodicalIF":10.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nrf2 activators for the treatment of rare iron overload diseases: From bench to bedside","authors":"Yimin Dong ,&nbsp;Meng Zheng ,&nbsp;Weizhong Ding ,&nbsp;Hanfeng Guan ,&nbsp;Jun Xiao ,&nbsp;Feng Li","doi":"10.1016/j.redox.2025.103551","DOIUrl":"10.1016/j.redox.2025.103551","url":null,"abstract":"<div><div>Iron overload and related oxidative damage are seen in many rare diseases, due to mutation of iron homeostasis-related genes. As a core regulator on cellular antioxidant reaction, Nrf2 can also decrease systemic and cellular iron levels by regulating iron-related genes and pathways, making Nrf2 activators very good candidates for the treatment of iron overload disorders. Successful examples include the clinical use of omaveloxolone for Friedreich's Ataxia and dimethyl fumarate for relapsing-remitting multiple sclerosis. Despite these uses, the therapeutic potentials of Nrf2 activators for iron overload disorders may be overlooked in clinical practice. Therefore, this study talks about the potential use, possible mechanisms, and precautions of Nrf2 activators in treating rare iron overload diseases. In addition, a combination therapy with Nrf2 activators and iron chelators is proposed for clinical reference, aiming to facilitate the clinical use of Nrf2 activators for more iron overload disorders.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103551"},"PeriodicalIF":10.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-omics approach reveals impaired lipid metabolism and oxidative stress in a zebrafish model of Alexander disease","authors":"Deianira Bellitto ,&nbsp;Matteo Bozzo ,&nbsp;Silvia Ravera ,&nbsp;Nadia Bertola ,&nbsp;Francesca Rosamilia ,&nbsp;Jessica Milia ,&nbsp;Paola Barboro ,&nbsp;Gabriela Coronel Vargas ,&nbsp;Donatella Di Lisa ,&nbsp;Laura Pastorino ,&nbsp;Francesca Lantieri ,&nbsp;Patrizio Castagnola ,&nbsp;Erika Iervasi ,&nbsp;Marco Ponassi ,&nbsp;Aldo Profumo ,&nbsp;Kateryna Tkachenko ,&nbsp;Camillo Rosano ,&nbsp;Simona Candiani ,&nbsp;Tiziana Bachetti","doi":"10.1016/j.redox.2025.103544","DOIUrl":"10.1016/j.redox.2025.103544","url":null,"abstract":"<div><div>Alexander disease (AxD) is a rare leukodystrophy caused by heterozygous mutations in the <em>GFAP</em> gene. To date, several <em>in vitro</em> and <em>in vivo</em> models have been generated in an attempt to unravel the main mechanisms underlying this complex disease. However, none of these models is suitable for investigating the global dysregulation caused by AxD. To address this shortcoming, we have generated a stable transgenic zebrafish line (zAxD) carrying the human GFAP p.R239C mutation, which is associated with severe phenotypes of AxD type I patients. We then performed transcriptomics and proteomics analyses on the whole larvae of our zAxD model, confirming the involvement of several pathways such as the immune system response and inflammation, oxidative stress, extracellular matrix, lipoxidation and lipid metabolism, which were previously reported in more limited omic studies. Interestingly, new pathways emerged as well, including tyrosine and butanoate metabolic processes. Biochemical assays confirmed alterations in cell respiration and lipid metabolism as well as elevated oxidative stress. These findings confirm the reliability of the zAxD model to apply a whole-organism approach to investigate the molecular basis of the disease.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103544"},"PeriodicalIF":10.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenium deficiency impedes maturation of parvalbumin interneurons, perineuronal nets, and neural network activity","authors":"Alexandru R. Sasuclark ,&nbsp;Marissa Watanabe ,&nbsp;Kai Roshto ,&nbsp;Victor W. Kilonzo ,&nbsp;Yiqiang Zhang ,&nbsp;Matthew W. Pitts","doi":"10.1016/j.redox.2025.103548","DOIUrl":"10.1016/j.redox.2025.103548","url":null,"abstract":"<div><div>Selenoproteins are fundamental players in redox signaling that are essential for proper brain development and function. They are indispensable for the vitality of GABAergic parvalbumin-expressing interneurons (PVIs), a cell type characterized by fast-spiking activity and heightened rates of metabolism. During development, PVIs are preferentially encapsulated by specialized extracellular matrix structures, termed perineuronal nets (PNNs), which serve to stabilize synaptic structure and act as protective barriers against redox insults. Consequently, alterations in PVIs and PNNs are well chronicled in neuropsychiatric disease, and evidence from animal models indicates that redox imbalance during adolescence impedes their maturation. Herein, we examined the influence of selenium on maturation of neural network structure and activity in primary cortical cultures. Cultures grown in selenium-deficient media exhibited reduced antioxidant activity, impaired PNN formation, and decreased synaptic input onto PVIs at 28 days <em>in vitro</em>, which coincided with increased oxidative stress. Parallel studies to monitor longitudinal maturation of <em>in vitro</em> electrophysiological activity were conducted using microelectrode arrays (MEA). Selenium content affected the electrophysiological profile of developing cultures, as selenium-deficient cultures exhibited impairments in long-term potentiation in conjunction with reduced spike counts for both network bursts and in response to stimulation. Finally, similar PNN deficits were observed in the cortex of mice raised on a selenium-deficient diet, providing corroborative evidence for the importance of selenium in PNN development. In sum, these findings show the vital role of selenium for the development of GABAergic inhibitory circuits.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103548"},"PeriodicalIF":10.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considerations for antibody-based detection of NRF2 in human cells","authors":"Alicja Dziadosz-Brzezińska ,&nbsp;Sara Kusiński ,&nbsp;Artur Piróg,&nbsp;Zuzanna Urban-Wójciuk,&nbsp;Monikaben Padariya,&nbsp;Umesh Kalathiya,&nbsp;Sachin Kote,&nbsp;Alicja Sznarkowska","doi":"10.1016/j.redox.2025.103549","DOIUrl":"10.1016/j.redox.2025.103549","url":null,"abstract":"<div><div>Based on the knockdown and overexpression experiments, it is accepted that in Tris-glycine SDS-PAGE human NRF2 migrates above 100 kDa, depending on the percentage of the gel. In 8 % Tris-glycine gel, monoclonal anti-NRF2 antibodies detect NRF2 signal as three bands migrating between 100 and 130 kDa. Here we used mass spectrometry to identify proteins immunoprecipitated by anti-NRF2 antibodies migrating in this range under steady state, upon NRF2 activator tert-BHQ and after translation inhibition with emetine. Our results show that three commercial monoclonal antibodies with epitopes in the center and in the C-terminus of NRF2 also bind calmegin, an ER-residing chaperone, that co-migrates with NRF2 in SDS-PAGE and gives stronger signal in western blot than NRF2. Calmegin has a much longer half life than NRF2 and resides in the cytoplasm, which differentiates it from NRF2. The most specific anti-NRF2 antibody in western blot, Cell Signaling Technology clone E5F1 is also specific in staining nuclear NRF2 in immunofluorescence. Other antibodies, that recognize calmegin in western blot, still can be specific for nuclear NRF2 in immunofluorescence, but require prior validation with NRF2 knockdown or knockout. These results appeal for caution and consideration when analyzing and interpreting results from antibody-based NRF2 detection.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103549"},"PeriodicalIF":10.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The covalent modification of STAT1 cysteines by sulforaphane promotes antitumor immunity via blocking IFN-γ-induced PD-L1 expression","authors":"Qing Shi ,&nbsp;Yajuan Liu ,&nbsp;Wanqi Yang ,&nbsp;Yao Li ,&nbsp;Chenji Wang ,&nbsp;Kun Gao","doi":"10.1016/j.redox.2025.103543","DOIUrl":"10.1016/j.redox.2025.103543","url":null,"abstract":"<div><div>Sulforaphane (SFN), a natural compound found in cruciferous vegetables, possesses well-documented antitumor properties. However, the precise functions and mechanisms of SFN in cancer suppression remain poorly understood. Here we provide evidence to demonstrate that SFN exerts more pronounced antitumor effects in immunocompetent mice compared to immunodeficient mice, suggesting the involvement of the host immune system in SFN-mediated tumor suppression. Furthermore, we reveal that SFN primarily acts through CD8⁺ cytotoxic T lymphocytes (CTLs) to enhance antitumor immunity by blocking the IFN-γ-mediated induction of PD-L1, a critical immune checkpoint receptor expressed in cancer cells. Importantly, our findings indicate that the suppression of PD-L1 expression by SFN is independent of the NRF2 protein stabilization pathway. Instead, SFN inhibits IFN-γ-mediated activation of STAT1, a key transcription factor involved in PD-L1 induction. Mechanistically, SFN covalently modifies specific cysteine residues (C155 and C174) on STAT1, resulting in the inhibition of its transcriptional activity. Notably, SFN-mediated downregulation of PD-L1 contributes to its antitumor immune effects, as demonstrated by enhanced anti-CTLA-4-mediated cytotoxicity. These findings indicate that SFN's antitumor effect extends beyond its direct cytotoxic properties, as it also actively engages the host immune system. This underscores SFN's immense potential as an immune-modulating agent in cancer therapy.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103543"},"PeriodicalIF":10.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}