Redox Biology最新文献

{"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}

{"title":"Supersulfides contribute to joint homeostasis and bone regeneration","authors":"Miki Maemura ,&nbsp;Masanobu Morita ,&nbsp;Seiryo Ogata ,&nbsp;Yoichi Miyamoto ,&nbsp;Tomoaki Ida ,&nbsp;Kazuhiro Shibusaka ,&nbsp;Soichiro Negishi ,&nbsp;Masahiro Hosonuma ,&nbsp;Taku Saito ,&nbsp;Jun Yoshitake ,&nbsp;Tsuyoshi Takata ,&nbsp;Tetsuro Matsunaga ,&nbsp;Eikan Mishima ,&nbsp;Uladzimir Barayeu ,&nbsp;Takaaki Akaike ,&nbsp;Fumiko Yano","doi":"10.1016/j.redox.2025.103545","DOIUrl":"10.1016/j.redox.2025.103545","url":null,"abstract":"<div><div>The physiological functions of supersulfides, inorganic and organic sulfides with sulfur catenation, have been extensively studied. Their synthesis is mainly mediated by mitochondrial cysteinyl-tRNA synthetase (CARS2) that functions as a principal cysteine persulfide synthase. This study aimed to investigate the role of supersulfides in joint homeostasis and bone regeneration. Using <em>Cars2</em>^AINK/+ mutant mice, in which the KIIK motif of CARS2 essential for supersulfide production was replaced with AINK, we evaluated the role of supersulfides in fracture healing and cartilage homeostasis during osteoarthritis (OA). Tibial fracture surgery was performed on the wild-type (<em>Cars2</em>^+/+) and <em>Cars2</em>^AINK/+ mice littermates. Bulk RNA-seq analysis for the osteochondral regeneration in the fracture model showed increased inflammatory markers and reduced osteogenic factors, indicative of impaired bone regeneration, in <em>Cars2</em>^AINK/+ mice. Destabilization of the medial meniscus (DMM) surgery was performed to produce the mouse OA model. Histological analyses with Osteoarthritis Research Society International and synovitis scores revealed accelerated OA progression in <em>Cars2</em>^AINK/+ mice compared with that in <em>Cars2</em>^+/+ mice. To assess the effects of supersulfides on OA progression, glutathione trisulfide (GSSSG) or saline was periodically injected into the mouse knee joints after the DMM surgery. Thus, supersulfides derived from CARS2 and GSSSG exogenously administered significantly inhibited inflammation and lipid peroxidation of the joint cartilage, possibly through suppression of ferroptosis, during OA development. This study represents a significant advancement in understanding anti-inflammatory and anti-oxidant functions of supersulfides in skeletal tissues and may have a clinical relevance for the bone healing and OA therapeutics.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103545"},"PeriodicalIF":10.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143452949","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 rhodamine-coordinated iridium complex to overcome cisplatin-resistant cancer via regulating mitochondrial function triggered apoptosis and ferroptosis","authors":"Juanjuan Li ,&nbsp;Guibin Gao ,&nbsp;Wenrui Ouyang ,&nbsp;Jinkun Huang ,&nbsp;Hongxing Liu ,&nbsp;Jin Li","doi":"10.1016/j.redox.2025.103536","DOIUrl":"10.1016/j.redox.2025.103536","url":null,"abstract":"<div><div>Modulating mitochondrial activity to regulate cancer cell homeostatic recycling presents a promising approach to overcome tumor resistance. Consequently, there is an urgent need for novel mitochondria-targeting agents and innovative strategies. We have developed [((η⁵-Cp∗)Ir(rhod)]²⁺2PF₆⁻ (<strong>Ir-rhod</strong>), a new mitochondria-targeted iridium complex that exhibits greater cytotoxicity towards A549R (cisplatin-resistant human lung cancer) cells compared to the ligand rhod. <strong>Ir-rhod</strong>'s mitochondrial targeting ability stems from both rhodamine's inherent mitochondrial affinity and the complex's positive bivalent nature. The positively charged <strong>Ir-rhod</strong> enters cells and is drawn to mitochondria due to the high transmembrane potential in tumor cells. Notably, rhodamine enables real-time observation of <strong>Ir-rhod</strong>'s dynamic distribution in vivo. <strong>Ir-rhod</strong> influences mitochondrial function, triggering tumor cell ferroptosis and apoptosis by modulating ACSL4 and GPX4. The targeting effect of <strong>Ir-rhod</strong> reduces its systemic toxicity in vivo, enhancing its biosafety profile. To our knowledge, <strong>Ir-rhod</strong> is an effective mitochondria-targeted Ir complex capable of inducing tumor cell death by disrupting mitochondrial function, offering a potent strategy to suppress cisplatin resistance in non-small cell lung cancer.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103536"},"PeriodicalIF":10.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143418482","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 protective role of GPX4 in naïve ESCs is highlighted by induced ferroptosis resistance through GPX4 expression","authors":"Seokwoo Park ,&nbsp;Mihn Jeong Park ,&nbsp;Eun-Ji Kwon ,&nbsp;Ji-Young Oh ,&nbsp;Yeon-Joon Chu ,&nbsp;Han Sun Kim ,&nbsp;Sunghyouk Park ,&nbsp;Tae Ha Kim ,&nbsp;Sung Won Kwon ,&nbsp;Yon Su Kim ,&nbsp;Hyuk-Jin Cha","doi":"10.1016/j.redox.2025.103539","DOIUrl":"10.1016/j.redox.2025.103539","url":null,"abstract":"<div><div>Ferroptosis, a form of oxidative cell death mediated by lipid peroxidation, is strictly regulated by glutathione peroxidase 4 (GPX4). Knockout of <em>Gpx4</em> results in embryonic lethality, highlighting its essential role in development. <em>In vitro</em>, mouse embryonic stem cells (mESCs), which represent the naïve pluripotent state, require β-mercaptoethanol (bME) to prevent cell death, unlike human embryonic stem cells, which represent the primed state. We hypothesized that naïve pluripotency is linked to a heightened susceptibility to ferroptosis due to unique metabolic demands and redox imbalances. In this study, we found that bME deprivation induces ferroptosis in naïve ESCs, as evidenced by lipid peroxidation; ferroptosis, however, is less evident in primed ESCs. Mechanistic analyses revealed that active oxidative phosphorylation (OXPHOS) in naïve ESCs increased mitochondrial reactive oxygen species. Consistent with the upregulation of <em>Gpx4</em> transcripts and OXPHOS-associated gene sets seen in the inner cell mass of blastocysts, stable GPX4 expression conferred resistance to ferroptosis induced by bME withdrawal. These results suggest that the unique redox and metabolic landscape of naïve ESCs highlits a potential requirement for GPX4 in maintaining naïve pluripotency, providing insights into early developmental processes and vulnerabilities.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103539"},"PeriodicalIF":10.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479180","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":"Astaxanthin protects against environmentally persistent free radical-induced oxidative stress in well-differentiated respiratory epithelium","authors":"Ayaho Yamamoto ,&nbsp;Peter D. Sly ,&nbsp;Lavrent Khachatryan ,&nbsp;Nelufa Begum ,&nbsp;Abrey J. Yeo ,&nbsp;Paul D. Robinson ,&nbsp;Stephania A. Cormier ,&nbsp;Emmanuelle Fantino","doi":"10.1016/j.redox.2025.103542","DOIUrl":"10.1016/j.redox.2025.103542","url":null,"abstract":"<div><div>Environmentally persistent free radicals (EPFRs) are combustion products present in substantial numbers on atmospheric particulate matter with half-lives of days to years. The mechanisms linking EPFR exposure and respiratory diseases are unclear, but likely involve oxidative stress. We investigated the mechanisms by which EPFR exposure impact on well-differentiated primary human nasal epithelial cells from subjects sensitive or resistant to oxidant stressors, cultured at an air-liquid interface. We found that EPFR exposure induced mitochondrial reactive oxygen species (mtROS) production; increased mitochondrial DNA copy number; down-regulated mucus production gene, Mucin-5AC (<em>MUC5AC</em>); up-regulated detoxifying gene, cytochrome P450 1A1 (<em>CYP1A1</em>), nuclear factor erythroid 2-related factor 2 (NRF2)-regulated antioxidant pathways including Sirtuin 1 (<em>SIRT1</em>)-Forkhead box O3 (<em>FOXO3</em>), mitophagy, PTEN-induced kinase 1 (<em>PINK1</em>), apoptosis, cyclin-dependent kinase inhibitor p21 (<em>p21</em>), and inflammation, C–C motif chemokine ligand 5 (<em>CCL5</em>). These results indicate that the well-differentiated respiratory epithelium can respond and activate redox reactions when exposed to sublethal concentrations of EPFRs. Increased susceptibility to EPFR exposure is conferred by failure to upregulate the mucin gene, <em>MUC5AC</em>, expression. Pre-treatment with astaxanthin prevented most of the negative impacts caused by EPFRs. Our results demonstrate that EPFRs can induce oxidative stress and cause damage to respiratory epithelium. A dietary antioxidant, astaxanthin, protected cells from EPFR-induced oxidant stress.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103542"},"PeriodicalIF":10.7,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403296","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":"Gp93 safeguards tissue homeostasis by preventing ROS-JNK-mediated apoptosis","authors":"Meng Xu ,&nbsp;Wanzhen Li ,&nbsp;Ruihong Xu ,&nbsp;Lixia Liu ,&nbsp;Zhihan Wu ,&nbsp;Wenzhe Li ,&nbsp;Chao Ma ,&nbsp;Lei Xue","doi":"10.1016/j.redox.2025.103537","DOIUrl":"10.1016/j.redox.2025.103537","url":null,"abstract":"<div><div>Reactive oxygen species (ROS) play a pivotal role in maintaining tissue homeostasis, yet their overabundance can impair normal cellular functions, induce cell death, and potentially lead to neurodegenerative disorders. This study identifies <em>Drosophila</em> Glycoprotein 93 (Gp93) as a crucial factor that safeguards tissue homeostasis and preserves normal neuronal functions by preventing ROS-induced, JNK-dependent apoptotic cell death. Firstly, loss of <em>Gp93</em> induces JNK-dependent apoptosis primarily through the induction of ROS. Secondary, neuro-specific depletion of <em>Gp93</em> results in ROS-JNK-mediated neurodegeneration. Thirdly, overexpression of Gp93 effectively curtails oxidative stress and neurodegeneration caused by paraquat exposure or the aging process. Furthermore, these functions of Gp93 can be substituted by its human ortholog, HSP90B1. Lastly, depletion of <em>HSP90B1</em> in cultured human cells triggers ROS production, JNK activation, and apoptosis. Thus, this study not only unveils a novel physiological function of Gp93, but also provides valuable insights for understanding the physiological and pathological functions of human HSP90B1.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103537"},"PeriodicalIF":10.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422671","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":"Oxidative stress-mediated abnormal polarization of decidual macrophages promotes the occurrence of atonic postpartum hemorrhage","authors":"Jiangxue Qu ,&nbsp;Hai Jiang ,&nbsp;Boyang Zhang ,&nbsp;Huifeng Shi ,&nbsp;Shuai Zeng ,&nbsp;Wei Wang ,&nbsp;Lian Chen ,&nbsp;Yangyu Zhao","doi":"10.1016/j.redox.2025.103530","DOIUrl":"10.1016/j.redox.2025.103530","url":null,"abstract":"<div><div>Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide. However, the mechanism underlying atonic PPH remains partially elucidated. Multi-omics revealed that differentially expressed proteins and metabolites were enriched in the immune-inflammation pathway in the vaginal blood of patients with atonic PPH. There was a pro-inflammatory immune microenvironment primarily activated by M1 macrophages in the decidua of the patients with atonic PPH, which presented as increased tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 levels and affected the contraction of the uterine smooth muscle. Besides, the decidual macrophage of the atonic PPH group exhibited increased oxidative stress. The PPH decidual cell culture medium induced the polarization of peripheral blood monocytes towards M1 macrophages while markedly increasing the levels of reactive oxygen species and superoxide anion radical. Using hydrogen peroxide (H₂O₂) to stimulate decidual macrophages induced a similar polarization state to that in atonic PPH samples, and the secretion of pro-inflammatory cytokines, such as TNF-α and IL-8, was significantly upregulated, which markedly impacted the expression of contraction-associated proteins (CAPs) in the uterine smooth muscle cells (uSMCs). The animal model suggested that H₂O₂ promoted the polarization of placental macrophages towards M1, affecting the levels of placental oxidative stress and inflammatory infiltration, and the contractility of uterine smooth muscle tissues. In summary, abnormal oxidative stress at the maternal-fetal interface induced the M1 polarization of decidual macrophages, causing the secretion of pro-inflammatory cytokines. TNF-α and IL-8 acted on uSMCs to inhibit CAP expression, inducing atonic PPH.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103530"},"PeriodicalIF":10.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479181","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":"Complex I superoxide anion production is necessary and sufficient for complex I inhibitor-induced dopaminergic neurodegeneration in Caenorhabditis elegans","authors":"Katherine S. Morton,&nbsp;Alex J. George,&nbsp;Joel N. Meyer","doi":"10.1016/j.redox.2025.103538","DOIUrl":"10.1016/j.redox.2025.103538","url":null,"abstract":"<div><div>Parkinson's Disease (PD) is the 2^nd most prevalent neurodegenerative disease, but there is currently no cure and limited understanding of the pathogenesis resulting in dopaminergic neurodegeneration. Inhibitors of electron transport chain Complex I (CI) have long been associated with and are now used to model PD, but CI inhibition results in multiple effects including ATP depletion and reactive oxygen species (ROS) generation. The lack of tools to isolate effects of CI inhibition have rendered it difficult to determine which mechanistic step is critical for CI inhibitor-induced dopaminergic neurodegeneration. Here we report that CI-derived superoxide anion, not ATP depletion, is the critical driver of CI inhibitor-induced dopaminergic neurodegeneration in the model organism <em>Caenorhabditis elegans</em>. We first use SuperNova, a light-activated ROS-generating protein, fused to CI to demonstrate that in absence of enzymatic inhibition CI-localized ROS production is sufficient to drive morphological damage and loss of function of the dopaminergic neurons. Second, we prevented superoxide anion production during exposure to the CI inhibitors rotenone and pyridaben and report a full rescue of CI inhibitor-induced degeneration and functional loss, without rescue of inhibitor-induced ATP depletion. We highlight the importance of mitochondrial superoxide anion generation in the pathogenesis of PD and build a foundation for further definition of the pathways activated by mitochondrial ROS that led to neuronal dysfunction and death. Identification of these underlying mechanisms allows for future prevention of toxicant exposure-induced PD based on mechanistic knowledge.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103538"},"PeriodicalIF":10.7,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403297","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":"Swimming exercise induces redox-lipid crosstalk to ameliorate osteoarthritis progression","authors":"Yubin Wu ,&nbsp;Mingzhuang Hou ,&nbsp;Yaoge Deng ,&nbsp;Xiaowei Xia ,&nbsp;Yang Liu ,&nbsp;Jianfeng Yu ,&nbsp;Chenqi Yu ,&nbsp;Huilin Yang ,&nbsp;Yijian Zhang ,&nbsp;Xuesong Zhu","doi":"10.1016/j.redox.2025.103535","DOIUrl":"10.1016/j.redox.2025.103535","url":null,"abstract":"<div><div>Conventional pharmacotherapy exhibits limited efficacy in halting cartilage degeneration, whereas exercise interventions have demonstrated promising protective effects against osteoarthritis (OA), albeit with unclear underlying mechanisms. This study investigated the beneficial effects of swimming in mitigating local joint damage through the enhancement of systemic antioxidant capacity. We found that overexpression of superoxide dismutase 3 (SOD3) could promote the elimination of extracellular reactive oxygen species (ROS) and preserve the cartilage extracellular matrix (C-ECM). Conversely, genetic deletion of SOD3 accelerated the loss of C-ECM and contributed to OA due to an imbalance in extracellular oxidative stress. Further investigation revealed that SOD3 could interact with CCAAT/enhancer binding protein β (C/EBPβ), leading to the inhibition of apolipoprotein E (APOE) transcription and subsequent APOE-induced cholesterol transport. Ultimately, we developed targeted extracellular vesicles (EVs) with high cartilage affinity for efficient and precise delivery of SOD3. Overall, this study elucidated the potential of exercise for degenerative joint disorders through SOD3-mediated extracellular antioxidation and cholesterol redistribution.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103535"},"PeriodicalIF":10.7,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403295","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":"Quantitative analysis of the proteome and protein oxidative modifications in primary human coronary artery endothelial cells and associated extracellular matrix","authors":"Shuqi Xu ,&nbsp;Christine Y. Chuang ,&nbsp;Clare L. Hawkins ,&nbsp;Per Hägglund ,&nbsp;Michael J. Davies","doi":"10.1016/j.redox.2025.103524","DOIUrl":"10.1016/j.redox.2025.103524","url":null,"abstract":"<div><div>Vascular endothelial cells (ECs) play a key role in physiology by controlling arterial contraction and relaxation, and molecular transport. EC dysfunction is associated with multiple pathologies. Here, we characterize the cellular and extracellular matrix (ECM) proteomes of primary human coronary artery ECs, from multiple donors, and oxidation/nitration products formed on these during cell culture, using liquid chromatography-mass spectrometry. In total ∼9900 proteins were identified in cells from 3 donors, with ∼7000 proteins per donor. Of these ∼5300 were consistently identified, indicating some heterogeneity across the donors, with age a possible cause. Multiple endogenous oxidation products were detected on both ECM and cellular proteins (and particularly endoplasmic reticulum species). In contrast, nitration was mostly detected on cell proteins and particularly cytoskeletal proteins, consistent with intracellular generation of nitrating agents, possibly from endothelial nitric oxide synthase (eNOS) or peroxidase enzymes. The modifications are ascribed to both physiological enzymatic activity (hydroxylation at proline/lysine; predominantly on ECM proteins and especially collagens) and the formation of reactive species (oxidation at tryptophan/tyrosine/histidine; nitration at tryptophan/tyrosine). The identified sites are present on a limited number of peptides (104 oxidized; 23 nitrated) from a modest number of proteins. A small number of proteins were detected with multiple modifications, consistent with these being selective and specific targets. Several nitrated peptides were consistently detected across all donors, and also in human smooth muscle cells suggesting that these are major targets in the vascular proteome. These data provide a ‘background’ proteome dataset for studies of endothelial dysfunction in disease.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"81 ","pages":"Article 103524"},"PeriodicalIF":10.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403308","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}