Redox Biology最新文献

{"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}

{"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}