Free Radical Biology and Medicine最新文献

{"title":"Androgen receptor alleviates doxorubicin-induced endoplasmic reticulum stress and myocardial injury by interacting with SERCA2a","authors":"Shuwei Ning ,&nbsp;Jianhui Li ,&nbsp;Mei He ,&nbsp;Yuexin Yu ,&nbsp;Zhikun Guo","doi":"10.1016/j.freeradbiomed.2025.02.010","DOIUrl":"10.1016/j.freeradbiomed.2025.02.010","url":null,"abstract":"<div><div>The clinical use of the anticancer drug doxorubicin (DOX) is limited due to its time- and dose-dependent cardiotoxicity. Therefore, there is an urgent need to explore the molecular mechanism and coping strategies for alleviating DOX-induced cardiotoxicity (DIC) and solve the difficulties in clinical application. The role and mechanism of androgen receptor (AR), which is the target of androgen, in DIC remain unclear. Here, we elucidated the molecular mechanisms of AR in DOX-induced cardiotoxicity. Inhibition of AR aggravated the DOX-induced cardiac function impairment, while the activation of AR showed obvious therapeutic effect and rescued cardiac function of rats. AR can physically interact with SERCA2a. Activation of AR participates in the regulation of DOX-induced myocardial injury by modulating SERCA2a, attenuating DOX-induced endoplasmic reticulum stress, improving calcium (Ca²⁺) cycling homeostasis, and inhibiting ROS levels and apoptosis, thereby participating in the regulation of DOX induced myocardial injury. Altogether, these findings reveal for the first time the relationship and role between AR and SERCA2a in regulating the progression of DIC, suggesting that AR may play a therapeutic role as a new target against DIC.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"230 ","pages":"Pages 127-137"},"PeriodicalIF":7.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rpl13a snoRNAs-regulated NADPH oxidase 1-dependent ROS generation: A novel RBC pathway mediating complement C3a deposition and triggering thrombosis in aging and venous blood clotting disorders","authors":"Waseem Chauhan,&nbsp;Shirin Ferdowsi,&nbsp;S.J. Sudharshan,&nbsp;Rahima Zennadi","doi":"10.1016/j.freeradbiomed.2025.02.008","DOIUrl":"10.1016/j.freeradbiomed.2025.02.008","url":null,"abstract":"<div><div>Adults older than 45 years old are at higher risk of developing venous blood clotting known as venous thrombosis/thromboembolism than a cohort &lt;45 years old. Complement activation, which can be mediated by oxidative stress, plays a central role in venous thrombosis. Yet, whether RBCs contribute to complement activation triggering thrombosis in aging and in patients with venous thrombosis/thromboembolism remains an open question. RBCs from healthy Mid-life stage (55–68 years old) adults and patients with venous thrombosis/thromboembolism showed higher deposition of the complement C3 and the anaphylatoxin C3a, and NADPH oxidase (Nox)1 expression than a younger cohort (21–30 years old). Increased C3/C3a deposition on RBCs from mid-life stage adults and patients with venous thrombosis/thromboembolism triggered prothrombin activation via Nox1-dependent reactive oxygen species (ROS) generation, and G protein-coupled receptor kinase 2 (GRK2) activation. Interaction of C3/C3a positive RBCs from mid-life stage adults with endothelial cells led to increased endothelial ROS production. TGF-β1-stimulated GRK2 and Nox1 activation in RBCs from the younger and older adults exacerbated RBC C3/C3a deposition and C3/C3a-mediated prothrombotic activation, which appears to result from ROS-mediated increased RBC phosphatidylserine exposure. Using human RBCs, and <em>Rpl13a</em> snoRNA knockout aged mice, we show that <em>Rpl13a</em> snoRNAs, the master regulators of ROS levels and oxidative stress response, regulate human and murine RBC C3a deposition and prothrombic activation in aging by modulating <em>Nox1</em> mRNA expression. <em>In vivo Rpl13a</em> snoRNA knockout in aged mice decreased thrombi size by blunting RBC C3a deposition, and RBCs-triggering prothrombin activation. These findings point out to a novel role of RBC <em>Rpl13a</em> snoRNAs in dysregulating RBC ROS-induced C3a deposition promoting venous thrombosis in aging.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"230 ","pages":"Pages 138-150"},"PeriodicalIF":7.1,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Penile endothelial dysfunction, impaired redox metabolism and blunted mitochondrial bioenergetics in diet-induced obesity: Compensatory role of H2O2","authors":"Alfonso Gómez del Val ,&nbsp;Ana Sánchez ,&nbsp;Óscar Freire-Agulleiro ,&nbsp;María Pilar Martínez ,&nbsp;Mercedes Muñoz ,&nbsp;Lucia Olmos ,&nbsp;Javier Sáenz Medina ,&nbsp;Simon Gabriel Comerma-Steffensen ,&nbsp;Ulf Simonsen ,&nbsp;Luis Rivera ,&nbsp;Miguel López ,&nbsp;Cristina Contreras ,&nbsp;Dolores Prieto","doi":"10.1016/j.freeradbiomed.2025.02.004","DOIUrl":"10.1016/j.freeradbiomed.2025.02.004","url":null,"abstract":"<div><h3>Objective</h3><div>Erectile dysfunction (ED) is considered an early manifestation of cardiovascular disease (CVD), endothelial dysfunction being the link between CVD and vasculogenic ED. Mitochondrial reactive oxygen species (mtROS) have been involved in the vascular complications of metabolic disorders. The aim of this study was to assess the impact of obesity on endothelial function, redox metabolism and mitochondrial bioenergetics of penile erectile tissue.</div></div><div><h3>Methods</h3><div>Wistar rats were fed a high-fat diet (HFD) or standard diet (STD), and penile vascular function was assessed in microvascular myographs. mtROS levels were measured by mitoSOX (O₂^.-) and Amplex Red (H₂O₂) fluorimetry, and the effect of the mitochondrial antioxidant mitoTempo on endothelium-dependent relaxations was tested. Mitochondrial respiration of intact microarteries was assessed with an Agilent Seahorse XF Pro analyzer, and the expression of mitochondria redox regulators was analysed by Western blot.</div></div><div><h3>Results</h3><div>Endothelium-dependent relaxations to acetylcholine (ACh) and to the mitoK_ATP channel activator BMS191095 were reduced in penile arteries from HFD. mtROS levels were significantly increased and associated with upregulation of the endothelial NADPH oxidase 4 (Nox4) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) in HFD erectile tissue. MitoTempo inhibited endothelial relaxations in control and HFD penile arteries. The bioenergetic profile was significantly reduced in HFD penile arteries compared to STD rats.</div></div><div><h3>Conclusions</h3><div>Mitochondrial dysfunction with impaired bioenergetics and reduced mitoK_ATP channel-mediated relaxation underlie endothelial and vascular dysfunction of erectile tissue in obesity, despite a compensatory mechanism that enhances Nox4-derived endothelial vasodilator mtROS. Therapeutic strategies aimed to stabilize mitochondria could restore redox balance and improve mitochondrial bioenergetics thus preventing oxidative stress and vascular dysfunction underlying metabolic disease associated ED.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"230 ","pages":"Pages 222-233"},"PeriodicalIF":7.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eight weeks of high-intensity interval training alters the tongue microbiome and impacts nitrate and nitrite levels in previously sedentary men","authors":"Annabel Simpson ,&nbsp;Andrea M. Pilotto ,&nbsp;Lorenza Brocca ,&nbsp;Raffaele Mazzolari ,&nbsp;Bob T. Rosier ,&nbsp;Miguel Carda-Diéguez ,&nbsp;Patricia Casas-Agustench ,&nbsp;Raul Bescos ,&nbsp;Simone Porcelli ,&nbsp;Alex Mira ,&nbsp;Chris Easton ,&nbsp;Fiona L. Henriquez ,&nbsp;Mia Burleigh","doi":"10.1016/j.freeradbiomed.2025.02.006","DOIUrl":"10.1016/j.freeradbiomed.2025.02.006","url":null,"abstract":"<div><div>Nitric oxide (∗NO) is a key signalling molecule, produced enzymatically via ∗NO synthases (NOS) or following the stepwise reduction of nitrate to nitrite via oral bacteria. Exercise training upregulates NOS expression and improves systemic health, but its effect on oral health, and more particularly the oral microbiome, has not been investigated. We used an exercise training study design to investigate changes in the tongue dorsum microbiome, and in nitrate and nitrite levels in the saliva, plasma and muscle, before, during and after an exercise training period.</div><div>Eleven untrained males (age 25 ± 5 years, mass 64.0 ± 11.2 kg, stature 171 ± 6 cm, <span><math><mrow><mover><mi>V</mi><mo>˙</mo></mover></mrow></math></span> O_2peak 2.25 ± 0.42 l min⁻¹) underwent 8-weeks of high-intensity interval training (HIIT), followed by 12-weeks of detraining. The tongue dorsum microbiome was examined using Pac-Bio long-read 16S rRNA sequencing. Nitrate and nitrite levels were quantified with high-performance liquid chromatography. Grouped nitrite-producing species did not change between any timepoints. However, HIIT led to changes in the microbiome composition, increasing the relative abundance of some, but not all, nitrite-producing species. These changes included a decrease in the relative abundance of nitrite-producing <em>Rothia</em> and a decrease in <em>Neisseria</em>, alongside changes in 6 other bacteria at the genus level (all <em>p</em> ≤ 0.05). At the species level, the abundance of 9 bacteria increased post-training (all <em>p</em> ≤ 0.05), 5 of which have nitrite-producing capacity, including <em>Rothia mucilaginosa</em> and <em>Streptococcus salivarius</em>. Post-detraining, 6 nitrite-producing species remained elevated relative to baseline. Nitrate increased in plasma (<em>p</em> = 0.03) following training. Nitrite increased in the saliva after training (<em>p</em> = 0.02) but decreased in plasma (<em>p</em> = 0.03) and muscle (<em>p</em> = 0.002).</div><div>High-intensity exercise training increased the abundance of several nitrite-producing bacteria and altered nitrate and nitrite levels in saliva, plasma, and muscle. Post-detraining, several nitrite-producing bacteria remained elevated relative to baseline, but no significant differences were detected in nitrate or nitrite levels. Switching from a sedentary to an active lifestyle alters both the microbiome of the tongue and the bioavailability of nitrate and nitrite, with potential implications for oral and systemic health.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"231 ","pages":"Pages 11-22"},"PeriodicalIF":7.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S-nitrosylation of peroxiredoxin 2 exacerbates hyperuricemia-induced renal injury through regulation of mitochondrial homeostasis","authors":"Fei Han ,&nbsp;Ya Dong ,&nbsp;Qiaoyan Liu ,&nbsp;Linling Song ,&nbsp;Hang Guo ,&nbsp;Lingling Zhu ,&nbsp;Bei Sun ,&nbsp;Wei Zhao ,&nbsp;Liming Chen","doi":"10.1016/j.freeradbiomed.2025.02.003","DOIUrl":"10.1016/j.freeradbiomed.2025.02.003","url":null,"abstract":"<div><div>Protein S-nitrosylation (SNO), a redox-based posttranslational modification of cysteine thiols, plays a crucial role in various signaling pathways. Peroxiredoxin 2 (PRDX2) is one of the most potent ROS scavenging proteins, providing protection against oxidative stress damage, with its function regulated by SNO. However, the precise role of SNO-PRDX2 in hyperuricemic nephropathy remains poorly understood. In this study, we identified PRDX2 as a highly S-nitrosylated target in hyperuricemic nephropathy using a biotin switch assay. The elevation of SNO-PRDX2 was observed in kidneys of hyperuricemic mice as well as in uric acid (UA)-treated human renal tubular epithelial (HK-2) cells. S-nitrosoglutathione (GSNO), an endogenous nitric oxide carrier, induced SNO modification of PRDX2, promoting mitochondrial dysfunction, oxidative stress, and cell apoptosis in HK-2 cells. Transfection with a plasmid containing a mutated cysteine 172 (Cys172) of PRDX2 yielded a decrease in SNO-PRDX2 levels in both hyperuricemic mice and UA-cultured HK-2 cells. Furthermore, administration of adeno-associated viruses carrying the Cys172-mutated PRDX2 significantly ameliorated renal interstitial fibrosis and reduced mitochondrial dysfunction, oxidative stress, and cell apoptosis in HUA-treated mice. In conclusion, our findings indicate that SNO modification of PRDX2 at Cys172 mediates HUA-induced kidney interstitial fibrosis, suggesting that SNO-PRDX2 may serve as a potential therapeutic target for HUA-induced renal injury.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"230 ","pages":"Pages 66-78"},"PeriodicalIF":7.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skin sensitizers enhance superoxide formation by polycyclic aromatic hydrocarbons via the aldo-keto reductase pathway","authors":"Oliver F. Eberle ,&nbsp;Frederick Hartung ,&nbsp;Paul Benndorf ,&nbsp;Thomas Haarmann-Stemmann","doi":"10.1016/j.freeradbiomed.2025.02.005","DOIUrl":"10.1016/j.freeradbiomed.2025.02.005","url":null,"abstract":"<div><div>Exposure to combustion-derived airborne polycyclic aromatic hydrocarbons (PAHs) may harm human skin, exacerbate cutaneous inflammatory diseases and accelerate skin aging. The toxicity of PAHs is unleashed upon their metabolic activation by cytochrome P450 (CYP) 1 monooxygenases, resulting in the formation of reactive intermediates that form mutagenic DNA adducts. Moreover, PAHs cause oxidative stress, which is primarily due to aldo-keto reductases (AKRs), such as AKR1C3, which convert CYP1-derived PAH-<em>trans</em>-diols to PAH-catechols. The catechols undergo autooxidation leading to the formation of reactive oxygen species (ROS) and PAH-quinones. The latter are highly reactive, mitotoxic and are reduced back to PAH-catechols, thus facilitating redox cycling. As AKR1C expression is inducible by other NRF2-stimulating chemicals, we tested the hypothesis that co-exposure of HaCaT keratinocytes to skin sensitizers and the PAH benzo[<em>a</em>]pyrene (BaP) enhances ROS formation. We observed a synergistic effect of the skin sensitizers on the BaP-induced expression of the NRF2 target genes heme oxygenase-1, sulfiredoxin-1 and AKR1C3. In fact, co-exposure to the skin sensitizers also enhanced the BaP-induced formation of superoxide anions. Intriguingly, the co-exposure-related ROS formation was abolished upon inhibition of either CYP1A1 or AKR1C3. Testing of additional skin-sensitizing compounds, differing in their mode of action, indicated that especially potent Michael acceptors enhance the toxicity of BaP by increasing AKR1C3 expression and, presumably, downstream BaP-quinone formation. Our study reveals potential health risks associated with the simultaneous exposure to common skin-sensitizing substances and ubiquitous PAHs, and implies a role for NRF2 in mediating PAH toxicity.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"230 ","pages":"Pages 50-57"},"PeriodicalIF":7.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “The H3K9 histone methyltransferase G9a modulates renal ischemia reperfusion injury by targeting Sirt1” [Free Radic. Biol. Med. 172 (2021) 123–135]","authors":"Hao Liu ,&nbsp;Wei Wang ,&nbsp;Xiaodong Weng ,&nbsp;Hui Chen ,&nbsp;Zhiyuan Chen ,&nbsp;Yang Du ,&nbsp;Xiuheng Liu ,&nbsp;Lei Wang","doi":"10.1016/j.freeradbiomed.2025.01.043","DOIUrl":"10.1016/j.freeradbiomed.2025.01.043","url":null,"abstract":"","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"230 ","pages":"Pages 320-321"},"PeriodicalIF":7.1,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triptolide alleviates acute lung injury by reducing mitochondrial dysfunction mediated ferroptosis through the STAT3/p53 pathway","authors":"Jia Zhou ,&nbsp;Sanzhong Li ,&nbsp;Yuting Yang ,&nbsp;Chaoqi Zhou ,&nbsp;Cheng Wang ,&nbsp;Zhenguo Zeng","doi":"10.1016/j.freeradbiomed.2025.02.001","DOIUrl":"10.1016/j.freeradbiomed.2025.02.001","url":null,"abstract":"<div><div>Acute lung injury (ALI) represents a severe clinical condition marked by intense pulmonary inflammation and complex pathogenic mechanisms. Triptolide, a potent anti-inflammatory agent derived from the plant Tripterygium wilfordii Hook. f., remains to be fully elucidated for its therapeutic efficacy in ALI. This study aimed to investigate the potential of triptolide in mitigating ALI by modulating ferroptosis and preserving mitochondrial function. Utilizing an ALI model induced by lipopolysaccharide (LPS) both in mice and BEAS-2B cells, we evaluated the impact of triptolide on lung injury, inflammatory cytokines, oxidative stress, and mitochondrial function. RNA sequencing, network pharmacology, molecular docking, and a thermal stability assay for cellular proteins (CETSA) were utilized to identify triptolide targets and pathways. Triptolide significantly alleviated LPS-induced pulmonary pathological changes, downregulated inflammatory cytokines including IL-6, IL-1β, and TNF-α, and reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels while increasing glutathione (GSH) and superoxide dismutase (SOD) activity. RNA sequencing revealed that triptolide upregulated SLC7A11 and inhibited ferroptosis. Network pharmacology and molecular docking identified the STAT3/p53 pathway as a key mediator of triptolide's action. CETSA confirmed that triptolide binds to and enhances the thermal stability of STAT3 and p53 proteins. This study is the first to elucidate that triptolide mitigates ALI by targeting the STAT3/p53 pathway, preserving mitochondrial function, and inhibiting ferroptosis. Collectively, these results propose that triptolide may serve as an effective therapeutic option for the treatment of ALI.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"230 ","pages":"Pages 79-94"},"PeriodicalIF":7.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma-activated saline hyperthermic perfusion-induced pyroptosis boosts peritoneal carcinomatosis immunotherapy","authors":"Miao Qi ,&nbsp;Xinyi Zhao ,&nbsp;Runze Fan ,&nbsp;Jiao Lin ,&nbsp;Zhuo Li ,&nbsp;Na Liu ,&nbsp;Xuejun Sun ,&nbsp;Dehui Xu ,&nbsp;Jianbao Zheng ,&nbsp;Dingxin Liu ,&nbsp;Renwu Zhou ,&nbsp;Mingzhe Rong ,&nbsp;Kostya (Ken) Ostrikov","doi":"10.1016/j.freeradbiomed.2025.02.002","DOIUrl":"10.1016/j.freeradbiomed.2025.02.002","url":null,"abstract":"<div><div>Peritoneal carcinomatosis (PC) is a common metastatic cancer with limited treatment options. Herein, we present a novel strategy for the combined treatment of PC involving plasma-activated saline (PAS) and hyperthermic intraperitoneal perfusion. PAS revealed a strong cytotoxic effect because of reactive oxygen species (ROS) in two-dimensional cultures and three-dimensional tumor spheroids of PC-related cell lines. Notably, PAS induced Gasdermin E (GSDME)-dependent pyroptosis and immunogenic cell death <em>in vitro.</em> PAS-enhanced hyperthermic intraperitoneal perfusion (PE-HIP) increased the number of CD3⁺, CD4⁺ and CD8⁺ T cells, while decreased the number of regulatory T cells, indicating that PAS stimulated T cell-based immune responses <em>in vivo</em>. Moreover, PE-HIP significantly inhibited tumor growth and improved survival in a PC-mice model, with no significant toxic side effects. Meanwhile, vaccination with PAS-induced cell pyroptosis activated systemic antitumor immunity to prevent subcutaneous tumor growth. Overall, PE-HIP can serve as a new approach for PC treatment by ROS-assisted cancer immunotherapy.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"230 ","pages":"Pages 177-189"},"PeriodicalIF":7.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox proteomic analysis of H2O2 -treated Jurkat cells and effects of bicarbonate and knockout of peroxiredoxins 1 and 2","authors":"Paul E. Pace ,&nbsp;Ling Fu ,&nbsp;Mark B. Hampton ,&nbsp;Christine C. Winterbourn","doi":"10.1016/j.freeradbiomed.2024.10.314","DOIUrl":"10.1016/j.freeradbiomed.2024.10.314","url":null,"abstract":"<div><div>Oxidation of thiol proteins and redox signaling occur in cells exposed to H₂O₂ but mechanisms are unclear. We used redox proteomics to seek evidence of oxidation of specific proteins either by a mechanism involving reaction of H₂O₂ with CO₂/bicarbonate to give the more reactive peroxymonocarbonate, or via a relay involving peroxiredoxins (Prdxs). Changes in oxidation state of specific Cys-SH residues on treating Jurkat T lymphoma cells with H₂O₂ were measured by isotopically labeling reduced thiols and analysis by mass spectrometry. The effects of bicarbonate and of knocking out either Prdx1 or Prdx2 were examined. Approximately 14,000 Cys-peptides were detected, of which ∼1 % underwent 2–10 fold loss in thiol content with H₂O₂. Those showing the most oxidation were not affected by the presence of bicarbonate or knockout of either Prdx. Consistent with previous evidence that bicarbonate potentiates inactivation of glyceraldehyde-3-phosphate dehydrogenase, the GAPDH active site Cys residues were significantly more sensitive to H₂O₂ when bicarbonate was present. Several other proteins were identified as promising candidates for further investigation. Although we identified some potential protein candidates for Prdx-dependent oxidation, most of the significant differences between KO and WT cells were seen in proteins for which H₂O₂ unexpectedly increased their CysSH content over untreated cells. We conclude that facilitation of protein oxidation by bicarbonate or Prdx-mediated relays is restricted to a small number of proteins and is insufficient to explain the majority of the oxidation of the cell thiols that occured in response to H₂O₂.</div></div>","PeriodicalId":12407,"journal":{"name":"Free Radical Biology and Medicine","volume":"227 ","pages":"Pages 221-232"},"PeriodicalIF":7.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}