Antioxidants & redox signaling最新文献_第2页

H₂S Donor SPRC Ameliorates Cardiac Aging by Suppression of JMJD3, a Histone Demethylase. H2S 供体 SPRC 通过抑制组蛋白去甲基化酶 JMJD3 来改善心脏衰老。

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-03-01 Epub Date: 2024-09-26 DOI: 10.1089/ars.2024.0605

Sha Li, Qixiu Li, Hong Xiang, Chenye Wang, Qi Zhu, Danping Ruan, Yi Zhun Zhu, Yicheng Mao

{"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":"Aims: 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. Results: In vitro, 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. In vivo, SPRC improved Dox-induced cardiac pathological structure and function. Overexpression of JMJD3 accelerated cardiomyocytes and cardiac senescence, whereas its knockdown in vitro 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. Innovations: 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. Conclusions: 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. Antioxid. Redox Signal. 42, 301-320.","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}

引用次数: 0

Lactate Dehydrogenase A Is a Novel Positive Regulator of Vascular Smooth Muscle Cell Ferroptosis During Aortic Dissection. 乳酸脱氢酶 A 是主动脉夹层过程中血管平滑肌细胞铁突变的新型正向调节因子

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-03-01 Epub Date: 2024-11-26 DOI: 10.1089/ars.2024.0585

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

{"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":"Aims: 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. Results: 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. Innovation and Conclusion: 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. Antioxid. Redox Signal. 42, 378-392.","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}

引用次数: 0

Spatiotemporal Characteristics Determining the Multifaceted Nature of Reactive Oxygen, Nitrogen, and Sulfur Species in Relation to Proton Homeostasis. 时空特征决定了活性氧、氮和硫物种（RONSS）与质子平衡的多面性。

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-03-01 Epub Date: 2024-03-27 DOI: 10.1089/ars.2023.0544

Hideo Yamasaki, Ryuuichi D Itoh, Kakeru B Mizumoto, Yuki S Yoshida, Joji M Otaki, Michael F Cohen

{"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":"Significance: 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. Recent Advances: 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. Critical Issues: 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. Future Directions: 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.","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}

引用次数: 0

Redox Control of Seed Germination is Mediated by the Crosstalk of Nitric Oxide and Reactive Oxygen Species. 种子萌发的氧化还原控制是由一氧化氮和活性氧的相互作用介导的

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-03-01 Epub Date: 2024-11-27 DOI: 10.1089/ars.2024.0699

Natalia V Bykova, Abir U Igamberdiev

{"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":"Significance: 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. Recent Advances: 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 via post-translational modification of proteins and mediation of phytohormonal responses. Critical Issues: 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. Future Directions: 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. Antioxid. Redox Signal. 42, 442-461.","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}

引用次数: 0

4-Octyl Itaconate Attenuates Cell Proliferation by Cellular Senescence via Glutathione Metabolism Disorders and Mitochondrial Dysfunction in Melanoma.

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-02-07 DOI: 10.1089/ars.2024.0629

Yoshikazu Hayashi, Ayaka Saeki, Shohei Yoshimoto, Ena Yano, Atsushi Yasukochi, Soi Kimura, Tomoe Utsunomiya, Kento Minami, Yuji Aso, Yuji Hatakeyama, Yi-Chen Lo, Masato Hirata, Eijiro Jimi, Tomoyo Kawakubo-Yasukochi

{"title":"4-Octyl Itaconate Attenuates Cell Proliferation by Cellular Senescence via Glutathione Metabolism Disorders and Mitochondrial Dysfunction in Melanoma.","authors":"Yoshikazu Hayashi, Ayaka Saeki, Shohei Yoshimoto, Ena Yano, Atsushi Yasukochi, Soi Kimura, Tomoe Utsunomiya, Kento Minami, Yuji Aso, Yuji Hatakeyama, Yi-Chen Lo, Masato Hirata, Eijiro Jimi, Tomoyo Kawakubo-Yasukochi","doi":"10.1089/ars.2024.0629","DOIUrl":"https://doi.org/10.1089/ars.2024.0629","url":null,"abstract":"Aims: Itaconate (IA) is synthesized in the citric acid cycle via cis-aconitate decarboxylase (ACOD1); however, its biological significance in cancer remains incompletely understood. In previous studies, 4-octyl itaconate (OI) was used as a membrane-permeable form of IA, but little detailed verification of the difference in biological activities between IA and OI exists. Here, we investigated the direct effects of IA and OI on melanoma. Results: The proliferation of melanoma cells treated with OI was significantly suppressed in vitro, and our transcriptomic analysis revealed drastic changes in the expression of glutathione metabolism-related genes in OI-treated cells. Indeed, OI treatment decreased intracellular glutathione levels, followed by increased production of reactive oxygen species and expression of γH2AX, a marker of DNA damage, and β-galactosidase, a marker of cellular senescence. We further showed that the mitochondrial respiratory capacity in B16 cells was significantly decreased by OI treatment. OI administration also suppressed the growth of B16 tumor transplants in vivo, and the expression of γH2AX was increased in tumor tissues of OI-treated mice. In addition, minimal effects of OI treatment were observed in melanocytes and normal tissues. We also proved that not only exogenous IA, which enters intracellularly, but also endogenous IA has little effect on melanoma proliferation activity, via an investigation using Acod1-overexpressing transfectants and Acod1-deficient mice. Conclusion: This work revealed that OI disrupts the antioxidant system via the collapse of glutathione metabolism and inhibits cancer cell proliferation. Antioxid. Redox Signal. 00, 000-000.","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390001","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}

引用次数: 0

GPx3 Promotes Functional Recovery after Spinal Cord Injury by Inhibiting Microglial Pyroptosis Through IRAK4/ROS/NLRP3 Axis.

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-02-03 DOI: 10.1089/ars.2024.0618

Zhongyuan Liu, Jiawei Shi, Kewu Tu, Hao Ma, Jiayu Chen, Xin Xiang, Peiqian Zou, Congrui Liao, Ruoting Ding, Zucheng Huang, Xinqiang Yao, Jianting Chen, Liang Wang, Zhongmin Zhang

{"title":"GPx3 Promotes Functional Recovery after Spinal Cord Injury by Inhibiting Microglial Pyroptosis Through IRAK4/ROS/NLRP3 Axis.","authors":"Zhongyuan Liu, Jiawei Shi, Kewu Tu, Hao Ma, Jiayu Chen, Xin Xiang, Peiqian Zou, Congrui Liao, Ruoting Ding, Zucheng Huang, Xinqiang Yao, Jianting Chen, Liang Wang, Zhongmin Zhang","doi":"10.1089/ars.2024.0618","DOIUrl":"https://doi.org/10.1089/ars.2024.0618","url":null,"abstract":"Aim: Spinal cord injury (SCI) is a catastrophic injury characterized by oxidative stress. Glutathione peroxidase 3 (GPx3) is an antioxidant enzyme that protects against immune responses in various diseases. However, the effects of GPx3 in SCI remains unclear. This study aimed to investigate the role of GPx3 in SCI and its underlying mechanisms. Results: We injected adeno-associated viruses to overexpress GPx3 in mice. Primary microglia and BV2 cells were used as in vitro models. We knocked down or overexpressed GPx3 in BV2 cells. Additionally, BV2 cells transfected with siIRAK4 were used to perform rescue experiments. A series of histological and molecular biological analyses were used to explore the role of GPx3 in SCI. Overexpression of GPx3 inhibited oxidative stress in mice, improving functional recovery after SCI. Similarly, LPS+ATP stimulation decreased GPx3 expression in microglia. Silencing of GPx3 elevated the generation of reactive oxygen species, increased the expression of IRAK4 and pro-inflammatory factors, and promoted pyroptosis in microglia. However, overexpression of GPx3 reversed these results. Moreover, silencing of IRAK4 alleviated these phenomena, which were upregulated by GPx3 deficiency. Innovation and Conclusion: Our results demonstrated that GPx3 plays a critical role in SCI by inhibiting microglial pyroptosis via the IRAK4/ROS/NLRP3 signaling pathway. Antioxid. Redox Signal. 00, 000-000.","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078477","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}

引用次数: 0

Suppression of CDK1/Drp1-Mediated Mitochondrial Fission Attenuates Dexamethasone-Induced Extracellular Matrix Deposition in the Trabecular Meshwork. 抑制 CDK1/Drp1 介导的线粒体分裂可减轻地塞米松诱导的小梁网细胞外基质沉积。

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-02-01 Epub Date: 2024-11-06 DOI: 10.1089/ars.2023.0502

Xizhi Deng, Min Zhu, Yang Liu, Nan Zhang, Pengyu Zhang, Wen Zeng, Min Ke

{"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":"Aims: 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. Results: 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 in vitro. 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. Innovation: This study illuminates the pathogenic mechanism linking mitochondrial dysfunction to ECM deposition in GIG. Our innovative approach revealed that Dex stimulates mitochondrial fission via CDK1-mediated p-Drp1s616 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. Conclusion: By targeting the CDK1/Drp1-driven mitochondrial fission process, we can counteract Dex-induced ECM deposition in the TM both in vivo and in vitro. Antioxid. Redox Signal. 42, 249-264.","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}

引用次数: 0

Where in the Tissues of Danio rerio Is More H₂O₂ Produced During Acute Hypoxia? 在急性缺氧时，丹瑞鱼组织的哪些部位会产生更多的 H2O2？

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-02-01 Epub Date: 2024-11-04 DOI: 10.1089/ars.2024.0563

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

{"title":"Where in the Tissues of Danio rerio 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":"The lack of oxygen (O2) causes changes in the cell functioning. Modeling hypoxic conditions in vitro is challenging given that different cell types exhibit different sensitivities to tissue O2 levels. We present an effective in vivo platform for assessing various tissue and organ parameters in Danio rerio 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 D. rerio 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 D. rerio under hypoxia. Antioxid. Redox Signal. 42, 292-300.","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}

引用次数: 0

Lipotoxicity Induces Cardiomyocyte Ferroptosis via Activating the STING Pathway. 脂肪毒性通过激活 STING 通路诱导心肌细胞铁变态反应

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-02-01 Epub Date: 2024-08-01 DOI: 10.1089/ars.2023.0510

Qian Chen, Yina Wang, Jiafu Wang, Xiaolan Ouyang, Junlin Zhong, Yao Huang, Zhuoshan Huang, Benrong Zheng, Long Peng, Xixiang Tang, Suhua Li

{"title":"Lipotoxicity Induces Cardiomyocyte Ferroptosis via Activating the STING Pathway.","authors":"Qian Chen, Yina Wang, Jiafu Wang, Xiaolan Ouyang, Junlin Zhong, Yao Huang, Zhuoshan Huang, Benrong Zheng, Long Peng, Xixiang Tang, Suhua Li","doi":"10.1089/ars.2023.0510","DOIUrl":"10.1089/ars.2023.0510","url":null,"abstract":"Objective: Lipotoxicity is a well-established contributor to cardiomyocyte death and heart damage, with ferroptosis being identified as a crucial death mode in cardiomyocyte disease. This study aims to explore the potential role and mechanism of ferroptosis in lipotoxicity-induced myocardial injury. Methods: Eight-week high-fat diet (HFD) Sprague-Dawley rat and H9c2 cardiomyocytes treated with palmitic acid (PA) were established for an in vivo and in vitro lipotoxic model. Ferrostatin-1 (Fer-1) and liproxstatin-1 (Lip-1) were used to inhibit ferroptosis. Myocardial-specific stimulator of interferon genes (STING) knockdown rat (Stingmyo-KD) with HFD was further introduced. Rat cardiac structure and function, cell viability, the level of lipid peroxidation, malondialdehyde (MDA), glutathione (GSH), mitochondrial function, ferroptosis-related proteins, and STING pathway-related proteins in H9c2 cells/myocardium were detected. Results: HFD rats with a ferroptosis inhibitor showed improved cardiac structure and function, reduced lipid peroxidation, and restored GSH, which was further confirmed in H9c2 cell. The time-dependent activation of the STING pathway following PA stimulation was observed. Knockdown of the expression of STING could reduce PA-induced cell death, lipid peroxidation, and MDA levels while restoring the GSH. In addition, both HFD Stingmyo-KD rats and HFD rats with systematic inhibition by the STING inhibitor exhibited mitigating lipotoxicity-induced myocardial ferroptosis and reducing myocardial injury. Innovation and Conclusion: These findings suggest that lipotoxicity can induce ferroptosis in cardiomyocytes through the activation of the STING pathway, providing new targets and strategies for the treatment of lipotoxicity cardiomyopathy. Antioxid. Redox Signal. 42, 184-198.","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"184-198"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603118","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}

引用次数: 0

HIF-1α/BNIP3-Mediated Endoplasmic Reticulum Degradation via Autophagy Protects Against Ischemia Reperfusion-Induced Acute Kidney Injury. HIF-1α/BNIP3通过自噬介导的内质网降解可防止缺血再灌注引起的急性肾损伤。

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-02-01 Epub Date: 2024-08-28 DOI: 10.1089/ars.2023.0467

Hao Zhao, Ming Yang, Yachun Han, Na Jiang, Yan Liu, Chenrui Li, Jinfei Yang, Shilu Luo, Chongbin Liu, Lin Sun, Fuyou Liu, Yu Liu

{"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":"Aims: 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. Results: In the present study, an in vivo 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 in vitro significantly increased BNIP3, autophagy and ER degradation, whereas inhibition of BNIP3 significantly reversed the effects of HIF-1α. In addition, the in vitro 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 in vitro. Innovation and Conclusion: These data indicate that HIF-1α/BNIP3-mediated ER degradation via autophagy in tubular cells protects against IR-induced AKI. Antioxid. Redox Signal. 42, 212-227.","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}

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