Antioxidants & redox signaling最新文献

{"title":"Dual Oxygen-Responsive Control by RegSR of Nitric Oxide Reduction in the Soybean Endosymbiont <i>Bradyrhizobium diazoefficiens</i>.","authors":"Andrea Jiménez-Leiva, Raquel A Juárez-Martos, Juan J Cabrera, María J Torres, Socorro Mesa, María J Delgado","doi":"10.1089/ars.2024.0710","DOIUrl":"10.1089/ars.2024.0710","url":null,"abstract":"<p><p><b><i>Aims:</i></b> To investigate the role of the RegSR-NifA regulatory cascade in the oxygen control of nitric oxide (NO) reduction in the soybean endosymbiont <i>Bradyrhizobium diazoefficiens</i>. <b><i>Results:</i></b> We have performed an integrated study of <i>norCBQD</i> expression and NO reductase activity in <i>regR</i>, <i>regS</i>₁, <i>regS</i>₂, <i>regS</i>_1/2, and <i>nifA</i> mutants in response to microoxia (2% O₂) or anoxia. An activating role of RegR and NifA was observed under anoxia. In contrast, under microaerobic conditions, RegR acts as a repressor by binding to a RegR box located between the -10 and -35 regions within the <i>norCBQD</i> promoter. In addition, both RegS₁ and RegS₂ sensors cooperated with RegR in repressing <i>norCBQD</i> genes. <b><i>Innovation:</i></b> NO is a reactive gas that, at high levels, acts as a potent inhibitor of symbiotic nitrogen fixation. In this paper, we report new insights into the regulation of NO reductase, the major enzyme involved in NO removal in rhizobia. This knowledge will be crucial for the development of new strategies and management practices in agriculture, in particular, for improving legume production. <b><i>Conclusion:</i></b> Our results demonstrate, for the first time, a dual control of the RegSR two-component regulatory system on <i>norCBQD</i> genes control in response to oxygen levels. <i>Antioxid. Redox Signal.</i> 42, 408-420.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"408-420"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045346","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":"Mitochondrial-Derived Signaling Mediates Differentiation of Parietal Epithelial Cells into Podocytes.","authors":"Minzhou Wang, Wangshu Wu, Jiayue Lu, Renhua Lu, Lulin Min, Ahui Song, Bingru Zhao, Ying Li, Kewei Xie, Leyi Gu","doi":"10.1089/ars.2024.0580","DOIUrl":"10.1089/ars.2024.0580","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Parietal epithelial cells (PECs) are potential stem cells within the glomerulus, migrating into site of podocyte loss to differentiate into podocytes. Little is known about the mechanism mediating differentiation of PECs into podocytes. <b><i>Results:</i></b> <i>In vitro</i> differentiation of PECs into podocytes led to upregulation of podocyte markers such as Wilms' tumor gene 1 (WT-1), Forkhead box C1 (FOXC1), synaptopodin and podocin, accompanied by increased mitochondrial abundance. Preincubation with a mitochondrial reactive oxygen species (ROS) inhibitor prevented all these events in PECs. <i>In vivo</i>, adriamycin (ADR)-treated mice exhibited albuminuria, decreased WT1 positive cells, and claudin-1 expressed in glomerular capillary tuft, as well as peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) overproduction in PECs. Expression of the ROS-related molecule nuclear factor erythroid 2-related factor 2 (Nrf2) and its target protein Brahma-related gene 1 (Brg1) increased during differentiation of PECs into podocytes. Suppressing Nrf2 or Brg1 reduced the differentiation of PECs, whereas overexpression had the opposite effect. Brg1 directly regulated WT-1 transcription in PECs. Activation of Nrf2 with bardoxolone-methyl (CDDO-Me) resulted in less proteinuria and more WT1 positive cells in ADR mice. PECs conditional human Nrf2 knock-in mice showed increased WT1 cell numbers. <b><i>Conclusion:</i></b> It concluded that mitochondria-derived ROS mediated differentiation of PECs into podocytes <i>via</i> Nrf2 and Brg1 signaling. <i>Antioxid. Redox Signal.</i> 42, 393-407.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"393-407"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103734","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":"Alterations in Mitochondrial Function in Pulmonary Vascular Diseases.","authors":"Samar Farha, Kewal Asosingh, Paul M Hassoun, John Barnard, Suzy Comhair, Andrew Reichard, Nicholas Wanner, Milena Radeva, Micheala A Aldred, Gerald J Beck, Erika Berman-Rosenzweig, Barry A Borlaug, J Emanuel Finet, Robert P Frantz, Gabriele Grunig, Anna R Hemnes, Nicholas Hill, Evelyn M Horn, Christine Jellis, Jane A Leopold, Reena Mehra, Margaret M Park, Franz P Rischard, W H Wilson Tang, Serpil C Erzurum","doi":"10.1089/ars.2024.0557","DOIUrl":"10.1089/ars.2024.0557","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Alterations of mitochondrial bioenergetics and arginine metabolism are universally present and mechanistically linked to pulmonary arterial hypertension (PAH), but there is little knowledge of arginine metabolism and mitochondrial functions across the different pulmonary hypertension (PH) groups. We hypothesize that abnormalities in mitochondrial functions are present across all PH groups and associated with clinical phenotypes. We test the hypothesis in PH patients and healthy controls from the Pulmonary Vascular Disease Phenomics Program cohort, who had comprehensive clinical phenotyping and follow-up for at least 4 years for death or transplant status. Mitochondrial transmembrane potential, superoxide production, and mass were measured by flow cytometry in fresh platelets. Metabolomics analysis was performed on plasma samples. Global arginine bioavailability was calculated as the ratio of arginine/(ornithine+citrulline). <b><i>Results:</i></b> Global arginine bioavailability is consistently lower than controls in all PH groups. Although the mitochondrial mass is similar across all PH groups and controls, superoxide production and transmembrane potential vary across groups. Mitochondrial superoxide is higher in group 1 PAH and lowest in group 3 compared with other groups, while transmembrane potential is lower in group 1 PAH than controls or group 3. The alterations in mitochondrial functions of group 1 PAH are associated with changes in fatty acid metabolism. Mitochondrial transmembrane potential in group 1 PAH is associated with transplant-free survival. <b><i>Conclusion:</i></b> While alterations in mitochondrial function are found in all PH groups, group 1 PAH has a unique mitochondrial phenotype with greater superoxide and lower transmembrane potential linked to fatty acid metabolism, and clinically to survival. <i>Antioxid. Redox Signal.</i> 42, 361-377.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"361-377"},"PeriodicalIF":6.1,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12344126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798984","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":"H₂S Donor SPRC Ameliorates Cardiac Aging by Suppression of JMJD3, a Histone Demethylase.","authors":"Sha Li, Qixiu Li, Hong Xiang, Chenye Wang, Qi Zhu, Danping Ruan, Yi Zhun Zhu, Yicheng Mao","doi":"10.1089/ars.2024.0605","DOIUrl":"10.1089/ars.2024.0605","url":null,"abstract":"<p><p><b><i>Aims:</i></b> S-propargyl-cysteine (SPRC) is an endogenous hydrogen sulfide (H₂S) donor obtained by modifying the structure of S-allyl cysteine in garlic. This study aims to investigate the effect of SPRC on mitigating cardiac aging and the involvement of jumonji domain-containing protein 3 (JMJD3), a histone demethylase, which represents the primary risk factor in major aging related diseases, in this process, elucidating the preliminary mechanism through which SPRC regulation of JMJD3 occurs. <b><i>Results:</i></b> <i>In vitro</i>, SPRC mitigated the elevated levels of reactive oxygen species, senescence-associated β-galactosidase, p53, and p21, reversing the decline in mitochondrial membrane potential, which represented a reduction in cellular senescence. <i>In vivo</i>, SPRC improved Dox-induced cardiac pathological structure and function. Overexpression of JMJD3 accelerated cardiomyocytes and cardiac senescence, whereas its knockdown <i>in vitro</i> reduced the senescence phenotype. The potential binding site of the upstream transcription factor of JMJD3, sheared X box binding protein 1 (XBP1s), was determined using online software. SPRC promoted the expression of cystathionine γ-lyase (CSE), which subsequently inhibited the IRE1α/XBP1s signaling pathway and decreased JMJD3 expression. <b><i>Innovations:</i></b> This study is the first to establish JMJD3 as a crucial regulator of cardiac aging. SPRC can alleviate cardiac aging by upregulating CSE and inhibiting endoplasmic reticulum stress pathways, which in turn suppress JMJD3 expression. <b><i>Conclusions:</i></b> JMJD3 plays an essential role in cardiac aging regulation, whereas SPRC can suppress the expression of JMJD3 by upregulating CSE, thus delaying cardiac aging, which suggests that SPRC may serve as an aging protective agent, and pharmacological targeting of JMJD3 may also be a promising therapeutic approach in age-related heart diseases. <i>Antioxid. Redox Signal.</i> 42, 301-320.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"301-320"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103733","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":"Lactate Dehydrogenase A Is a Novel Positive Regulator of Vascular Smooth Muscle Cell Ferroptosis During Aortic Dissection.","authors":"Xin Feng, Xin Yi, Bo Huo, Hanshen Luo, Jingjie Chen, Xian Guo, Ze-Min Fang, Fu-Han Gong, Xiang Wei, Ding-Sheng Jiang, Yue Chen","doi":"10.1089/ars.2024.0585","DOIUrl":"10.1089/ars.2024.0585","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Vascular smooth muscle cell (VSMC) ferroptosis is a pivotal event in the process of aortic dissection (AD), and a number of agents have a protective role against AD by inhibiting VSMC ferroptosis. While glycolysis is an ancient pathway related to almost all biological processes, its precise involvement in VSMC ferroptosis and AD remains unclear. <b><i>Results:</i></b> In this study, bioinformatics analysis revealed that glycolysis-related molecules and pathways were involved in VSMC ferroptosis and AD. We focused on the key enzyme of glycolysis, lactate dehydrogenase A (LDHA), and found that LDHA overexpression promoted ferroptosis and lipid peroxidation in cystine deprivation- or imidazole ketone erastin-treated VSMCs and vice versa. Clinical specimens showed a negative correlation between elevated LDHA levels in dissected aortae and ferroptosis-related molecules glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and ferroptosis suppressor protein 1 (FSP1). In VSMC ferroptosis, LDHA overexpression led to the suppression of GPX4, SLC7A11, and FSP1. Furthermore, the interaction between LDHA and nuclear factor (erythroid-derived 2)-like 2 (NRF2) was identified, and the overexpression or agonist of NRF2 reversed the contribution of LDHA on VSMC ferroptosis and lipid peroxidation. <b><i>Innovation and Conclusion:</i></b> These results highlight a significant association between LDHA and VSMC ferroptosis in AD development mediated through NRF2. These findings present LDHA as a potential target for AD intervention by inhibiting its expression. <i>Antioxid. Redox Signal.</i> 42, 378-392.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"378-392"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738144","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":"Spatiotemporal Characteristics Determining the Multifaceted Nature of Reactive Oxygen, Nitrogen, and Sulfur Species in Relation to Proton Homeostasis.","authors":"Hideo Yamasaki, Ryuuichi D Itoh, Kakeru B Mizumoto, Yuki S Yoshida, Joji M Otaki, Michael F Cohen","doi":"10.1089/ars.2023.0544","DOIUrl":"10.1089/ars.2023.0544","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) act as signaling molecules, regulating gene expression, enzyme activity, and physiological responses. However, excessive amounts of these molecular species can lead to deleterious effects, causing cellular damage and death. This dual nature of ROS, RNS, and RSS presents an intriguing conundrum that calls for a new paradigm. <b><i>Recent Advances:</i></b> Recent advancements in the study of photosynthesis have offered significant insights at the molecular level and with high temporal resolution into how the photosystem II oxygen-evolving complex manages to prevent harmful ROS production during the water-splitting process. These findings suggest that a dynamic spatiotemporal arrangement of redox reactions, coupled with strict regulation of proton transfer, is crucial for minimizing unnecessary ROS formation. <b><i>Critical Issues:</i></b> To better understand the multifaceted nature of these reactive molecular species in biology, it is worth considering a more holistic view that combines ecological and evolutionary perspectives on ROS, RNS, and RSS. By integrating spatiotemporal perspectives into global, cellular, and biochemical events, we discuss local pH or proton availability as a critical determinant associated with the generation and action of ROS, RNS, and RSS in biological systems. <b><i>Future Directions:</i></b> The concept of localized proton availability will not only help explain the multifaceted nature of these ubiquitous simple molecules in diverse systems but also provide a basis for new therapeutic strategies to manage and manipulate these reactive species in neural disorders, pathogenic diseases, and antiaging efforts.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"421-441"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970786","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 Control of Seed Germination is Mediated by the Crosstalk of Nitric Oxide and Reactive Oxygen Species.","authors":"Natalia V Bykova, Abir U Igamberdiev","doi":"10.1089/ars.2024.0699","DOIUrl":"10.1089/ars.2024.0699","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Seed germination and seedling establishment are characterized by changes in the intracellular redox state modulated by accelerated production of nitric oxide (NO) and reactive oxygen species (ROS). Redox regulation and enhanced accumulation of NO and ROS, approaching excessively high levels during seed imbibition, are critically important for breaking endodormancy and inducing germination. <b><i>Recent Advances:</i></b> Upon depletion of oxygen under the seed coat, NO is produced anaerobically in the reductive pathway associated mainly with mitochondria, and it participates in the energy metabolism of the seed until radicle protrusion. NO turnover involves nitrate reduction to nitrite in the cytosol, nitrite reduction to NO in mitochondria, and NO oxygenation in the cytosol in the reaction involving the hypoxically induced class 1 phytoglobin. In postgerminative degradation of seed tissues, NO and ROS are involved in redox signaling <i>via</i> post-translational modification of proteins and mediation of phytohormonal responses. <b><i>Critical Issues:</i></b> The crosstalk between the cellular redox potential, NO, ROS, and phytohormones integrates major physiological processes related to seed germination. Intensive accumulation of NO and ROS during imbibition is critically important for breaking seed dormancy. Upon oxygen depletion, NO and other nitrous oxides (NOx) are produced anaerobically and support energy metabolism prior to radicle protrusion. <b><i>Future Directions:</i></b> The turnover of NOx and ROS is determined by the intracellular redox balance, and it self-controls redox and energy levels upon germination. The particular details, regulation of this process, and its physiological significance remain to be established. <i>Antioxid. Redox Signal.</i> 42, 442-461.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"442-461"},"PeriodicalIF":5.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738146","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":"Suppression of CDK1/Drp1-Mediated Mitochondrial Fission Attenuates Dexamethasone-Induced Extracellular Matrix Deposition in the Trabecular Meshwork.","authors":"Xizhi Deng, Min Zhu, Yang Liu, Nan Zhang, Pengyu Zhang, Wen Zeng, Min Ke","doi":"10.1089/ars.2023.0502","DOIUrl":"10.1089/ars.2023.0502","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Deposition of extracellular matrix (ECM) in the trabecular meshwork (TM), as induced by dexamethasone (Dex), is believed to play an important role in the onset of glucocorticoid-induced glaucoma (GIG). Abnormal ECM deposition is a consequence of mitochondrial dysfunction. We aimed to clarify how mitochondrial dysfunction leads to ECM deposition within the TM and to support the development of novel therapeutic strategies. <b><i>Results:</i></b> In primary human TM cells (pHTMCs) and a Dex acetate-induced murine model of GIG, glucocorticoid administration stimulated both mitochondrial fission and ECM deposition. Excessive mitochondrial fission leads to dysfunction and the overexpression of ECM proteins in pHTMCs. Notably, when pHTMCs were treated with the dynamin-related protein 1 (Drp1) inhibitor Mdivi-1 or with Drp1 siRNA, we observed a marked reduction in Dex-induced mitochondrial damage and ECM proteins <i>in vitro</i>. Furthermore, in C57BL/6J mice, treatment with Mdivi-1 mitigated mitochondrial damage and blocked ECM deposition within the TM. We then used Ro3306 to inhibit the cyclin-dependent kinase (CDK)1-mediated phosphorylation of Drp1 at Ser 616, which restored mitochondrial function and diminished Dex-induced ECM protein expression in pHTMCs. <b><i>Innovation:</i></b> This study illuminates the pathogenic mechanism linking mitochondrial dysfunction to ECM deposition in GIG. Our innovative approach revealed that Dex stimulates mitochondrial fission <i>via</i> CDK1-mediated p-Drp1^s616 overexpression, which drives ECM accumulation. It offered a novel therapeutic strategy for reducing ECM protein expression by inhibiting excessive mitochondrial fission and restoring mitochondrial function. <b><i>Conclusion:</i></b> By targeting the CDK1/Drp1-driven mitochondrial fission process, we can counteract Dex-induced ECM deposition in the TM both <i>in vivo</i> and <i>in vitro</i>. <i>Antioxid. Redox Signal.</i> 42, 249-264.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"249-264"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888297","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":"Where in the Tissues of <i>Danio rerio</i> Is More H₂O₂ Produced During Acute Hypoxia?","authors":"Anastasia D Sergeeva, Anastasiya S Panova, Alexandra D Ivanova, Yulia V Khramova, Ksenia I Morozova, Daria A Kotova, Anastasia V Guryleva, Demid D Khokhlov, Ilya V Kelmanson, Aleksandr V Vasilev, Alexander I Kostyuk, Alexey V Semyanov, Vladimir A Oleinikov, Vsevolod V Belousov, Alexander S Machikhin, Nadezda A Brazhe, Dmitry S Bilan","doi":"10.1089/ars.2024.0563","DOIUrl":"10.1089/ars.2024.0563","url":null,"abstract":"<p><p>The lack of oxygen (O₂) causes changes in the cell functioning. Modeling hypoxic conditions <i>in vitro</i> is challenging given that different cell types exhibit different sensitivities to tissue O₂ levels. We present an effective <i>in vivo</i> platform for assessing various tissue and organ parameters in <i>Danio rerio</i> larvae under acute hypoxic conditions. Our system allows simultaneous positioning of multiple individuals within a chamber where O₂ level in the water can be precisely and promptly regulated, all while conducting microscopy. We applied this approach in combination with a genetically encoded pH-biosensor SypHer3s and a highly H₂O₂-sensitive HyPer7 biosensor. Hypoxia causes H₂O₂ production in areas of brain, heart, and skeletal muscles, exclusively in the mitochondrial matrix; it is noteworthy that H₂O₂ does not penetrate into the cytosol and is neutralized in the matrix upon reoxygenation. Hypoxia causes pronounced tissue acidosis, expressed by a decrease in pH by 0.4-0.6 units everywhere. Using imaging photoplethysmography, we measured in <i>D. rerio</i> larvae real-time heart rate decrease under conditions of hypoxia and subsequent reoxygenation. Our observations in this experimental system lead to the hypothesis that mitochondria are the only source of H₂O₂ in cells of <i>D. rerio</i> under hypoxia. <i>Antioxid. Redox Signal.</i> 42, 292-300.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"292-300"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858878","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":"HIF-1α/BNIP3-Mediated Endoplasmic Reticulum Degradation via Autophagy Protects Against Ischemia Reperfusion-Induced Acute Kidney Injury.","authors":"Hao Zhao, Ming Yang, Yachun Han, Na Jiang, Yan Liu, Chenrui Li, Jinfei Yang, Shilu Luo, Chongbin Liu, Lin Sun, Fuyou Liu, Yu Liu","doi":"10.1089/ars.2023.0467","DOIUrl":"10.1089/ars.2023.0467","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Endoplasmic reticulum (ER) degradation via autophagy is a process that maintains ER homeostasis when cells are in a state of stress and is associated with many diseases; however, the role of hypoxia inducible factor-1α (HIF-1α)-mediated ER degradation and the related regulatory pathway in acute kidney injury (AKI) still needs to be further established. <b><i>Results:</i></b> In the present study, an <i>in vivo</i> AKI model was induced in mice via the ischemia-reperfusion (IR) method. The results revealed that HIF-1α and BNIP3 were increased, and autophagy and ER degradation were activated in the kidneys of AKI mice, whereas HIF-1α knockout significantly inhibited BNIP3, autophagy and ER degradation, accompanied by aggravated kidney injury. Overexpression of HIF-1α <i>in vitro</i> significantly increased BNIP3, autophagy and ER degradation, whereas inhibition of BNIP3 significantly reversed the effects of HIF-1α. In addition, the <i>in vitro</i> inhibition of autophagy with chloroquine significantly reversed the effects of HIF-1α on cell apoptosis. Moreover, selectively overexpressing BNIP3 on the ER membrane significantly increased ER degradation via autophagy and decreased cell apoptosis <i>in vitro</i>. <b><i>Innovation and Conclusion:</i></b> These data indicate that HIF-1α/BNIP3-mediated ER degradation via autophagy in tubular cells protects against IR-induced AKI. <i>Antioxid. Redox Signal.</i> 42, 212-227.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"212-227"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888295","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}