Redox Biology最新文献

{"title":"Extracellular vesicle-packaged GBP2 from macrophages aggravates sepsis-induced acute lung injury by promoting ferroptosis in pulmonary vascular endothelial cells","authors":"Zhixi Li ,&nbsp;Yue Bu ,&nbsp;Cheng Wang ,&nbsp;Yongjing Yu ,&nbsp;Lei Han ,&nbsp;Chang Liu ,&nbsp;Guangmin Chen ,&nbsp;Chenglong Li ,&nbsp;Yan Zhang ,&nbsp;Hang Cao ,&nbsp;Zhaoxue Ma ,&nbsp;Ziyong Yue","doi":"10.1016/j.redox.2025.103614","DOIUrl":"10.1016/j.redox.2025.103614","url":null,"abstract":"<div><div>Macrophages play a critical role in the development of sepsis-induced acute lung injury (si-ALI), with extracellular vesicles (EVs) acting as crucial mediators. However, the effects and mechanisms of macrophage-derived EVs on si-ALI remain unclear. This study demonstrated that macrophage-derived EVs induce endothelial ferroptosis and barrier disruption during sepsis. Through proteomic sequencing and reanalysis of transcriptomic and single-cell sequencing data, guanylate-binding protein 2 (GBP2) was identified as a key EV molecule. Elevated GBP2 expression was observed in EVs and monocytes from the peripheral blood of sepsis patients, in LPS-stimulated THP-1 and RAW264.7 cells and their secreted EVs, and in macrophages within the lungs of CLP mice. Additionally, GBP2 expression in EVs showed a positive correlation with vascular barrier injury biomarkers, including ANGPT2, Syndecan-1, and sTM. Modulating GBP2 levels in macrophage-derived EVs affected EV-induced ferroptosis in endothelial cells. The mechanism by which GBP2 binds directly to OTUD5 and promotes GPX4 ubiquitination was elucidated using RNA interference, adeno-associated virus transfection, and endothelial-specific Gpx4 knockout mice. A high-throughput screening of small-molecule compounds targeting GBP2 was conducted. Molecular docking, molecular dynamics simulations, and cellular thermal shift assays further confirmed that Plantainoside D (PD) has a potent binding affinity for GBP2. PD treatment inhibited the interaction between GBP2 and OTUD5, leading to a reduction in GPX4 ubiquitination. Further research revealed that PD treatment enhanced the pulmonary protective effects of GBP2 inhibition. In conclusion, this study explored the role of EV-mediated signaling between macrophages and pulmonary vascular endothelial cells in si-ALI, highlighting the GBP2-OTUD5-GPX4 axis as a driver of endothelial ferroptosis and lung injury. Targeting this signaling axis presents a potential therapeutic strategy for si-ALI.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103614"},"PeriodicalIF":10.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724884","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":"Hemoglobin in the brain frontal lobe tissue of patients with Alzheimer’s disease is susceptible to reactive nitrogen species-mediated oxidative damage","authors":"M.J. Smallwood ,&nbsp;M. Abu Alghayth ,&nbsp;A.R. Knight ,&nbsp;K. Tveen-Jensen ,&nbsp;A.R. Pitt ,&nbsp;C.M. Spickett ,&nbsp;D. Llewellyn ,&nbsp;G. Pula ,&nbsp;A. Wearn ,&nbsp;A. Vanhatalo ,&nbsp;A.M. Jones ,&nbsp;P. Francis ,&nbsp;E. Coulthard ,&nbsp;P.G. Kehoe ,&nbsp;P.G. Winyard","doi":"10.1016/j.redox.2025.103612","DOIUrl":"10.1016/j.redox.2025.103612","url":null,"abstract":"<div><div>Brain inflammation in Alzheimer’s disease (AD) involves reactive nitrogen species (RNS) generation. Protein contents of 3-nitrotyrosine, a product of RNS generation, were assessed in frontal lobe brain homogenates from patients with AD, patients with vascular dementia (VaD) and non-dementia (ND) controls. Western blotting revealed a dominant 15 kDa nitrated protein band in both dementia (AD/VaD) and ND frontal lobe brain tissue. Surprisingly, this protein band was identified by mass spectrometry as hemoglobin, an erythrocytic protein. The same band stained positively when western blotted using an anti-hemoglobin antibody. On western blots, the median (IQR) normalized staining intensity for 3-nitrotyrosine in hemoglobin was increased in both AD [1.71 (1.20–3.05) AU] and VaD [1.50 (0.59–3.04) AU] brain tissue compared to ND controls [0.41 (0.09–0.75) AU] (Mann-Whitney <em>U</em> test: AD v ND, P &lt; 0.0005; VaD v ND, P &lt; 0.05; n = 11). The median normalized staining of the nitrated hemoglobin band was higher in advanced AD patients compared with early-stage AD (P &lt; 0.005). The median brain tissue NO₂⁻ levels (nmol/mg protein) were significantly higher in AD samples than in ND controls (P &lt; 0.05). Image analysis of western blots of lysates from peripheral blood erythrocytes suggested that hemoglobin nitration was increased in AD compared to ND (P &lt; 0.05; n = 4 in each group). Total protein-associated 3-nitrotyrosine was measured by an electrochemiluminescence-based immunosorbent assay, but showed no statistically significant differences between AD, VaD and ND. Females showed larger increases in hemoglobin nitration and NO₂⁻ levels between disease and control groups compared to males, although the group sizes in these sub-analyses were small. In conclusion, the extent of hemoglobin nitration was increased in AD and VaD brain frontal lobe tissue compared with ND. We propose that reactive nitrogen species-mediated damage to hemoglobin may be involved in the pathogenesis of AD.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103612"},"PeriodicalIF":10.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759611","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":"Revisiting insulin-stimulated hydrogen peroxide dynamics reveals a cytosolic reductive shift in skeletal muscle","authors":"Carlos Henríquez-Olguín ,&nbsp;Samantha Gallero ,&nbsp;Anita Reddy ,&nbsp;Kaspar W. Persson ,&nbsp;Farina L. Schlabs ,&nbsp;Christian T. Voldstedlund ,&nbsp;Gintare Valentinaviciute ,&nbsp;Roberto Meneses-Valdés ,&nbsp;Casper M. Sigvardsen ,&nbsp;Bente Kiens ,&nbsp;Edward T. Chouchani ,&nbsp;Erik A. Richter ,&nbsp;Thomas E. Jensen","doi":"10.1016/j.redox.2025.103607","DOIUrl":"10.1016/j.redox.2025.103607","url":null,"abstract":"<div><div>The intracellular redox state is crucial for insulin responses in peripheral tissues. Despite the longstanding belief that insulin signaling increases hydrogen peroxide (H₂O₂) production leading to reversible oxidation of cysteine thiols, evidence is inconsistent and rarely involves human tissues. In this study, we systematically investigated insulin-dependent changes in subcellular H₂O₂ levels and reversible cysteine modifications across mouse and human skeletal muscle models. Utilizing advanced redox tools—including genetically encoded H₂O₂ sensors and non-reducing immunoblotting—we consistently observed no increase in subcellular H₂O₂ levels following insulin stimulation. Instead, stoichiometric cysteine proteome analyses revealed a selective pro-reductive shift in cysteine modifications affecting insulin transduction related proteins, including Cys179 on GSK3β and Cys416 on Ras and Rab Interactor 2 (RIN2). Our findings challenge the prevailing notion that insulin promotes H₂O₂ generation in skeletal muscle and suggest that an insulin-stimulated pro-reductive shift modulates certain aspects of insulin signal transduction.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103607"},"PeriodicalIF":10.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785255","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":"Absence of astrocytic ceruloplasmin reverses the senescence process with aging of learning and memory abilities","authors":"Zhong-Da Li ,&nbsp;Shaomeng Kang ,&nbsp;Haiyan Li ,&nbsp;Peng Yu ,&nbsp;Ruikun Xie ,&nbsp;Chenchen Li ,&nbsp;Qi Jing ,&nbsp;Zhengzheng Gong ,&nbsp;Li Li ,&nbsp;Zhengning Li ,&nbsp;Mengyu Geng ,&nbsp;Zihan Zhang ,&nbsp;Yang Li ,&nbsp;Yan-Zhong Chang","doi":"10.1016/j.redox.2025.103611","DOIUrl":"10.1016/j.redox.2025.103611","url":null,"abstract":"<div><div>Ceruloplasmin (CP) is a multi-copper ferroxidase mainly synthesized by liver, secreted into the peripheral blood, playing a critical role in regulating the iron homeostasis. In the central nervous system (CNS), the CP expressed by astrocytes plays an important role in the transportation of iron from the blood across the blood-brain barrier (BBB) into the brain. Our previous study showed that conditional knockout of astrocytic CP with Cre-LoxP system (<em>Cp</em>^{<em>Gfap</em>}<em>cKO</em>) not only improved the learning and memory abilities of elderly mice, but also impaired the learning and memory abilities of young mice. In order to further investigate the effects of CP on learning and memory with aging, we constructed mice model with tamoxifen-induced astrocyte specific knockout of CP, induced CP knockout at 12 months old, and observed the effects on mouse learning and memory at 18 months old. We were delighted to found that ablation of astrocytic CP by tamoxifen at 12 months old could similarly enhance the learning, memory and recognition abilities in 18-month-old mice. Iron deposition in the hippocampus associated with aging was mitigated, leading to a reduction in oxidative stress. The MAPK/JNK pathway exhibited attenuation, while the PI3K/Akt/GSK3 pathway showed enhancement. This combination is expected to result in the reduction of the phosphorylation level of MYC and the elevation of the nuclear translocation of MYC, which might then contribute to reduced cellular senescence. Additionally, the ROS/MAPK/Erk and ROS/MAPK/p38 pathways-dependent cell apoptosis in hippocampus was diminished. The hallmarks of Alzheimer's Disease (AD) were all significantly reduced. Ultimately, the alleviated cellular senescence along with the reduction in AD-related markers, coincided with an improvement in learning, memory, and recognition abilities. These findings further elucidated the role of CP in brain iron metabolism, offering a novel target and strategy for the prevention and treatment of neurodegenerative diseases, such as AD associated with aging.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103611"},"PeriodicalIF":10.7,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143767709","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":"Oncogenic KRAS addiction states differentially influence MTH1 expression and 8-oxodGTPase activity in lung adenocarcinoma","authors":"Beatriz Mateo-Victoriano ,&nbsp;Govindi J. Samaranayake ,&nbsp;Sheela Pokharel ,&nbsp;Gracy Jenifer Sahayanathan ,&nbsp;Christina Jayaraj ,&nbsp;Clara I. Troccoli ,&nbsp;Dionysios C. Watson ,&nbsp;Michael G. Mohsen ,&nbsp;Yan Guo ,&nbsp;Eric T. Kool ,&nbsp;Priyamvada Rai","doi":"10.1016/j.redox.2025.103610","DOIUrl":"10.1016/j.redox.2025.103610","url":null,"abstract":"<div><div>The efficacy of strategies targeting oncogenic RAS, prevalent in lung adenocarcinoma (LUAD), is limited by rapid adaptive resistance mechanisms. These include loss of RAS addiction and hyperactivation of downstream signaling pathways, such as PI3K/AKT. We previously reported that oncogenic RAS-driven LUAD cells possess an enhanced reliance on MTH1, the mammalian 8-oxodGTPase, to prevent genomic incorporation of oxidized nucleotides, and that MTH1 depletion compromises tumorigenesis and oncogenic signaling. Here, we show that elevated MTH1 correlates with poor prognosis in LUAD and that its redox-protective 8-oxodGTPase activity is variably regulated in KRAS-addicted vs. non-addicted states. Multiple oncogenic KRAS mutants or overexpression of wildtype (wt) KRAS increased MTH1 expression. Conversely, KRAS depletion or its inhibition by AMG-510 (sotorasib) decreased MTH1 in KRASG12C-addicted LUAD cells. Separation-of-function MEK/ERK1/2-activating mutants recapitulated the elevated MTH1 expression induced by oncogenic RAS in wt KRAS LUAD cells. However, upon inhibition of the MEK/ERK1/2 pathway, compensatory AKT activation maintained MTH1 expression. Indeed, elevated AKT signaling maintained high MTH1 expression even when KRAS oncoprotein was low. We previously reported that cancer cells possess variable MTH1-specific and MTH1-independent 8-oxodGTPase activity levels. Whereas both ERK1/2 and AKT could regulate MTH1 protein levels in KRAS-addicted cells, only AKT signaling was associated with elevated MTH1-specific 8-oxodGTPase activity under KRAS-low or KRAS non-addicted states. Our studies suggest that despite loss of KRAS dependency, LUAD cells retain the requirement for high MTH1 8-oxodGTPase activity due to redox vulnerabilities associated with AKT signaling. Thus, MTH1 may serve as a novel orthogonal vulnerability in LUAD that has lost KRAS addiction.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103610"},"PeriodicalIF":10.7,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143759610","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":"Oncogene-induced senescence mitochondrial metabolism and bioenergetics drive the secretory phenotype: further characterization and comparison with other senescence-inducing stimuli","authors":"Inés Marmisolle ,&nbsp;Eliana Chacón ,&nbsp;Santiago Mansilla ,&nbsp;Santiago Ruiz ,&nbsp;Mariana Bresque ,&nbsp;Jennyfer Martínez ,&nbsp;Ricardo Iván Martínez-Zamudio ,&nbsp;Utz Herbig ,&nbsp;Jie Liu ,&nbsp;Toren Finkel ,&nbsp;Carlos Escande ,&nbsp;Laura Castro ,&nbsp;Celia Quijano","doi":"10.1016/j.redox.2025.103606","DOIUrl":"10.1016/j.redox.2025.103606","url":null,"abstract":"<div><div>Cellular senescence is characterized by proliferation arrest and a senescence-associated secretory phenotype (SASP), that plays a role in aging and the progression of various age-related diseases. Although various metabolic alterations have been reported, no consensus exists regarding mitochondrial bioenergetics. Here we compared mitochondrial metabolism of human fibroblasts after inducing senescence with different stimuli: the oxidant hydrogen peroxide (H₂O₂), the genotoxic doxorubicin, serial passage, or expression of the H-RAS^G12V oncogene (RAS).</div><div>In senescence induced by H₂O₂, doxorubicin or serial passage a decrease in respiratory control ratio (RCR) and coupling efficiency was noted, in relation to control cells. On the contrary, oncogene-induced senescent cells had an overall increase in respiration rates, RCR, spare respiratory capacity and coupling efficiency. In oncogene-induced senescence (OIS) the increase in respiration rates was accompanied by an increase in fatty acid catabolism, AMPK activation, and a persistent DNA damage response (DDR), that were not present in senescent cells induced by either H₂O₂ or doxorubicin. Inhibition of AMPK reduced mitochondrial oxygen consumption and secretion of proinflammatory cytokines in OIS.</div><div>Assessment of enzymes involved in acetyl-CoA metabolism in OIS showed a 3- to 7.5-fold increase in pyruvate dehydrogenase complex (PDH), a 40% inhibition of mitochondrial aconitase, increased phosphorylation and activation of ATP-citrate lyase (ACLY), and inhibition of acetyl-CoA carboxylase (ACC). There was also a significant increase in expression and nuclear levels of the deacetylase sirtuin 6 (SIRT6). These changes can influence the sub-cellular distribution of acetyl-CoA and modulate protein acetylation reactions in the cytoplasm and nuclei. In fact, ACLY inhibition reduced histone 3 acetylation (H3K9Ac) in OIS and secretion of SASP components.</div><div>In summary, our data show marked heterogeneity in mitochondrial energy metabolism of senescent cells, depending on the inducing stimulus, reveal new metabolic features of oncogene-induced senescent cells and identify AMPK and ACLY as potential targets for SASP modulation.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103606"},"PeriodicalIF":10.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735158","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":"Protein post-translational modification crotonylation of TXN and GLO1 in artery and vein grafts for coronary artery surgery","authors":"Wen-Tao Sun ,&nbsp;Huan-Xin Chen ,&nbsp;Hai-Tao Hou ,&nbsp;Hong-Mei Xue ,&nbsp;Qin Yang ,&nbsp;Guo-Wei He","doi":"10.1016/j.redox.2025.103608","DOIUrl":"10.1016/j.redox.2025.103608","url":null,"abstract":"<div><div>A key problem in coronary artery bypass grafting (CABG) is the lower long-term patency of the saphenous vein (SV) compared to internal thoracic artery (ITA). The potential strategies to improve the long-term patency of the vein graft include developing drugs to block unfavorable pathways in the vein and even to change the protein structure of the vein towards arterial structure. It is therefore important to understand the differences of the protein structure between arterial and venous grafts. Using post-translational modification (PTM) proteomics, we systematically investigated differences between ITA and SV with regard to a vascular stenosis-related PTM crotonylation.</div><div>Crotonylome and PTM crotonylation in paired ITA and SV segments (n = 150) from patients undergoing CABG surgery were performed by proteomics analysis with further validation. To elucidate the underlying mechanisms, we focused on three crotonylated enzymatic proteins with anti-oxidative effects-thioredoxin (TXN), glyoxalase 1 (GLO1), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) - whose crotonylation patterns were systematically investigated. The functional validation was performed using both site-mutation experiments in HEK293 cells and pharmacological inhibitors in <em>ex vivo</em> cultured ITA/SV tissue specimens.</div><div>Comprehensive crotonyl-proteomics demonstrated 3652 proteins are differentially-expressed and 411 proteins are differentially-crotonylated in ITA/SV segments. In the identified crotonylated proteins, SV demonstrated significantly higher levels compared to ITA. Notably, SV showed higher crotonylation levels on TXN-K3, GLO1-K157, and GAPDH-K61, which were associated with decreased enzymatic activity, elevated methylglyoxal (MGO) accumulation, and increased oxidative stress. Inhibition of CREB-binding protein (CBP) reversed oxidative stress in SV by suppressing crotonylation of the three enzymes. In Hek293 cells, both site-specific and comprehensive crotonylation decreased the activities of TXN/GLO1/GAPDH, which in turn triggered the accumulation of MGO. Overexpression of histone deacetylases HDAC1 and HDAC3 showed the opposite effect, restoring enzyme function.</div><div>This study is the first to reveal significant differences in PTM crotonylation between human ITA and SV, shedding light on the biological mechanisms underlying the functional disparities between these grafts. These differences impact the enzymatic activity of key proteins involved in oxidative stress, providing insights into the molecular basis of graft performance. Importantly, these findings form a scientific basis for developing specific methods including new anti-oxidative drugs and gene therapy to target on crotonylation in the vein graft in order to improve the long-term graft patency.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103608"},"PeriodicalIF":10.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704458","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":"Interaction between redox regulation, immune activation, and response to treatment in HER2+ breast cancer","authors":"Paulo Luz ,&nbsp;Sofia Ramos ,&nbsp;Maria José Oliveira ,&nbsp;João G. Costa ,&nbsp;Nuno Saraiva ,&nbsp;Ana S. Fernandes","doi":"10.1016/j.redox.2025.103609","DOIUrl":"10.1016/j.redox.2025.103609","url":null,"abstract":"<div><div>In HER2+ breast cancer (BC), neoadjuvant therapy represents an ideal scenario for translational research, considering pathological complete response (pCR) as an endpoint. In these patients, achieving pCR after neoadjuvant therapy is associated with a better prognosis. However, biomarkers are needed to tailor optimal treatment for each patient. Evaluating tumour-infiltrating lymphocytes (TILs) has gained attention in predicting pCR. In the context of metastatic disease, TILs also appear to play a role in predicting outcomes. The interaction between the presence of TILs and reactive oxygen species (ROS) remains an area to be explored. ROS are critical for tumour cell homeostasis, and different levels can trigger differential biological responses in cancer cells and their microenvironment. Nevertheless, the influence of ROS on treatment efficacy and prognosis in patients with HER2+ BC remains to be elucidated. In this article, we reviewed the interplay between treatment response, immune system activation, and ROS production in HER2+ BC and suggested novel areas of intervention and research. We also present a bioinformatic analysis demonstrating that the altered expression of several redox-related genes could be associated with the prevalence of immune cell populations in the tumour microenvironment and with patient survival. New biomarkers are thus suggested and should be further explored to tailor the best treatment to each patient.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103609"},"PeriodicalIF":10.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143747179","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":"Melatonin rescues cell respiration impaired by hypoxia/reoxygenation in aortic endothelial cells and affects the mitochondrial bioenergetics targeting the F1FO-ATPase","authors":"Cristina Algieri ,&nbsp;Chiara Bernardini ,&nbsp;Antonia Cugliari ,&nbsp;Silvia Granata ,&nbsp;Fabiana Trombetti ,&nbsp;Patrycja Anna Glogowski ,&nbsp;Micaela Fabbri ,&nbsp;Giampaolo Morciano ,&nbsp;Gaia Pedriali ,&nbsp;Paolo Pinton ,&nbsp;Salvatore Nesci","doi":"10.1016/j.redox.2025.103605","DOIUrl":"10.1016/j.redox.2025.103605","url":null,"abstract":"<div><div>Melatonin is evaluated as a potential molecular therapy to counteract mitochondrial dysfunction caused by hypoxia/reoxygenation (H/R) in aortic endothelial cells (pAECs). The mitochondrial permeability transition pore (mPTP) opening undergoes a desensitizing action coupled with a reduction of superoxide anion production in mitochondria treated with melatonin. The effect on mPTP has been attributed to the direct interaction of melatonin with the hydrophilic F₁ domain of Ca²⁺-activated F₁F_O-ATPase. Mutual exclusion analysis highlights an overlapping binding site between melatonin and the specific F₁ inhibitor NBD-Cl. The results are corroborated by melatonin inhibition of ATPase activity of the purified F₁ domain in the presence of Ca²⁺, but not in the presence of natural cofactor Mg²⁺. Moreover, the impairment of bioenergetics parameters in pAECs metabolism and the increase of oxidative stress arising by H/R injury have been rescued in cells protected by melatonin treatment.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103605"},"PeriodicalIF":10.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682775","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":"Proximal tubular deletion of superoxide dismutase-2 reveals disparate effects on kidney function in diabetes","authors":"Inez A. Trambas ,&nbsp;Lilliana Bowen ,&nbsp;Vicki Thallas-Bonke ,&nbsp;Matthew Snelson ,&nbsp;Karly C. Sourris ,&nbsp;Adrienne Laskowski ,&nbsp;Michel Tauc ,&nbsp;Isabelle Rubera ,&nbsp;Guoping Zheng ,&nbsp;David C.H. Harris ,&nbsp;Phillip Kantharidis ,&nbsp;Takahiko Shimizu ,&nbsp;Mark E. Cooper ,&nbsp;Sih Min Tan ,&nbsp;Melinda T. Coughlan","doi":"10.1016/j.redox.2025.103601","DOIUrl":"10.1016/j.redox.2025.103601","url":null,"abstract":"<div><div>There is a large body of evidence implicating mitochondrial reactive oxygen species (ROS) overproduction and oxidative stress in the development of diabetic kidney disease and the deficiency of mitochondrial antioxidant systems in the kidney, such as manganese superoxide dismutase (MnSOD/SOD2) have been identified. The proximal tubules of the kidney are densely packed with mitochondria thereby providing energy via oxidative phosphorylation in order to drive active transport for proximal tubular reabsorption of solutes from the glomerular filtrate. We hypothesized that maintenance of MnSOD function in the proximal tubules would be critical to maintain kidney health in diabetes. Here, we induced targeted deletion of SOD2 in the proximal tubules of the kidney in <em>Ins2</em>^Akita diabetic mice (SOD^ptKO mice) and show that 20 weeks of SOD2 deletion leads to no major impairment of kidney function and structure, despite these mice displaying enhanced albuminuria and kidney lipid peroxidation (8-isoprostanes). Plasma cystatin C, which is a surrogate marker of glomerular filtration was not altered in SOD^ptKO diabetic mice and histological assessment of the kidney cortex revealed no change in kidney fibrosis. Thus, our findings suggest that deletion of SOD2 in the proximal tubular compartment of the kidney induces a more subtle phenotype than expected, shedding light on the involvement of SOD2 and the proximal tubular compartment in the pathogenesis of diabetic kidney disease.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"82 ","pages":"Article 103601"},"PeriodicalIF":10.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675591","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}