Antioxidants & redox signaling最新文献

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}

引用次数: 0

CCAAT/Enhancer-Binding Protein Beta Nitration Participates in Hyperhomocysteinemia-Induced Cardiomyocyte Autophagic Flux Blockage by Inhibiting Transcription Factor EB Transcription. CCAAT/增强子结合蛋白β -硝化通过抑制转录因子EB转录参与高同型半胱氨酸血症诱导的心肌细胞自噬通量阻断

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-02-01 Epub Date: 2025-01-09 DOI: 10.1089/ars.2023.0517

Jiayin Chai, Jiahui Xu, Shangyue Zhang, Wenjing Yan, Shuai Chen, Xinyu Zhu, Chenghua Luo, Wen Wang

{"title":"CCAAT/Enhancer-Binding Protein Beta Nitration Participates in Hyperhomocysteinemia-Induced Cardiomyocyte Autophagic Flux Blockage by Inhibiting Transcription Factor EB Transcription.","authors":"Jiayin Chai, Jiahui Xu, Shangyue Zhang, Wenjing Yan, Shuai Chen, Xinyu Zhu, Chenghua Luo, Wen Wang","doi":"10.1089/ars.2023.0517","DOIUrl":"10.1089/ars.2023.0517","url":null,"abstract":"Aims: Autophagy is a protective mechanism of cardiomyocytes. Hyperhomocysteinemia (HHcy) elevates oxidative and nitrosative stress levels, leading to an abnormal increase in nitration protein, possibly leading to abnormal autophagy regulation in cardiomyocytes. However, the regulatory effect of HHcy on autophagy at the post-translational modification level is still unclear. Here, we aimed to explore the regulatory mechanism of HHcy on transcription factor EB (TFEB) and nitration of CCAAT/enhancer-binding protein beta (C/EBPβ), a transcriptional repressor of Tfeb, on autophagy in cardiomyocytes. Results: In this study, we established the HHcy rat model by feeding a 2.5% (w/w) methionine diet. The nitration level of C/EBPβ was increased in HHcy, which promoted the entry of C/EBPβ into the nucleus, enhanced the transcriptional suppressive effect of C/EBPβ on Tfeb, and induced insufficient autophagy in cardiomyocytes. Furthermore, we confirmed that the Tyr 274 site of C/EBPβ could undergo nitration induced by HHcy. Once C/EBPβ was nitrated on the Tyr 274 site, the nuclear translocation of C/EBPβ and transcription suppressor function of C/EBPβ on Tfeb were enhanced. Innovation and Conclusion: We find that C/EBPβ is a transcriptional repressor of Tfeb, and HHcy induces the nitration at the Tyr 274 site of C/EBPβ, leading to autophagic flux blockage in cardiomyocytes. These data indicated that nitrated C/EBPβ might be a potential therapeutic target against HHcy-induced autophagy insufficiency of cardiomyocytes. Antioxid. Redox Signal. 42, 165-183.","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"165-183"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142943257","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

Nitric Oxide Is Required for Primary Nitrate Response in Arabidopsis: Evidence for S-Nitrosation of NLP7. 一氧化氮是拟南芥初级硝酸盐反应所必需的：NLP7 S-硝化作用的证据。

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-02-01 Epub Date: 2023-09-29 DOI: 10.1089/ars.2022.0210

Andrés Nejamkin, Fiorella Del Castello, Lorenzo Lamattina, Natalia Correa-Aragunde, Noelia Foresi

{"title":"Nitric Oxide Is Required for Primary Nitrate Response in Arabidopsis: Evidence for S-Nitrosation of NLP7.","authors":"Andrés Nejamkin, Fiorella Del Castello, Lorenzo Lamattina, Natalia Correa-Aragunde, Noelia Foresi","doi":"10.1089/ars.2022.0210","DOIUrl":"10.1089/ars.2022.0210","url":null,"abstract":"Aims: Nitrogen (N) is a necessary nutrient for plant development and seed production, with nitrate (NO3-) serving as the primary source of N in soils. Although several molecular players in plant responses to NO3- signaling were unraveled, it is still a complex process with gaps that require further investigation. The aim of our study is to analyze the role of nitric oxide (NO) in the primary nitrate response (PNR). Results: Using a combination of genetic and pharmacological approaches, we demonstrate that NO is required for the expression of the NO3--regulated genes nitrate reductase 1 (NIA1), nitrite reductase (NIR), and nitrate transporters (nitrate transporter 1.1 [NRT1.1] and nitrate transporter 2.1 [NRT2.1]) in Arabidopsis. The PNR is impaired in the Arabidopsis mutant noa1, defective in NO production. Our results also show that PHYTOGLOBIN 1 (PHYTOGLB1), involved in NO homeostasis, is rapidly induced during PNR in wild type (wt) but not in the mutants of the nitrate transceptor NTR1.1 and the transcription factor nodule inception-like protein 7 (NLP7), suggesting that the NRT1.1-NLP7 cascade modulates PHYTOGLB1 gene expression. Biotin switch experiments demonstrate that NLP7, the PNR-master regulator, is S-nitrosated in vitro. Depletion of NO during PNR intensifies the decrease in reactive oxygen species levels and the rise of catalase (CAT) and ascorbate peroxidase (APX) enzyme activity. Conclusion and Innovation: NO, a by-product of NO3- metabolism and a well-characterized signal molecule in plants, is an important player in the PNR.","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"280-291"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10027101","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

Does Deteriorating Antioxidant Defense and Impaired γ-Glutamyl Cycle Induce Oxidative Stress and Hemolysis in Individuals with Sickle Cell Disease? 抗氧化防御能力下降和γ-谷氨酰循环受损是否会诱发镰状细胞病患者的氧化应激和溶血？

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-02-01 Epub Date: 2024-07-29 DOI: 10.1089/ars.2024.0594

Shruti Bhatt, Amit Kumar Mohapatra, Apratim Sai Rajesh, Satyabrata Meher, Alo Nag, Pradip Kumar Panda, Ranjan Kumar Nanda, Suman Kundu

{"title":"Does Deteriorating Antioxidant Defense and Impaired γ-Glutamyl Cycle Induce Oxidative Stress and Hemolysis in Individuals with Sickle Cell Disease?","authors":"Shruti Bhatt, Amit Kumar Mohapatra, Apratim Sai Rajesh, Satyabrata Meher, Alo Nag, Pradip Kumar Panda, Ranjan Kumar Nanda, Suman Kundu","doi":"10.1089/ars.2024.0594","DOIUrl":"10.1089/ars.2024.0594","url":null,"abstract":"Sickle cell disease (SCD) affects two-thirds of African and Indian children. Understanding the molecular mechanisms contributing to oxidative stress may be useful for therapeutic development in SCD. We evaluated plasma elemental levels of Indian SCD patients, trait, and healthy controls (n = 10 per group) via inductively coupled plasma mass spectrometry. In addition, erythrocyte metabolomics of Indian SCD and healthy (n = 5 per group) was carried out using liquid chromatography-mass spectrometry. Followed by assessment of antioxidant defense enzymes namely glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) in erythrocytes and plasma of Indian SCD patients (n = 31) compared with trait (n = 10) and healthy (n = 10). In SCD plasma an elevated plasma 24 Mg, 44Ca, 66Zn, 208Pb, 39K and reduced 57Fe, 77Se, and 85Rb levels indicated higher hemolysis and anemia. Erythrocyte metabolome of SCD patients clustered separately from healthy revealed 135 significantly deregulated metabolic features, including trimethyllysine, pyroglutamate, glutathione, aminolevulinate, and d-glutamine, indicating oxidative stress and membrane fragility. Repressed GR, SOD, and CAT activities were observed in SCD patients of which GR and CAT activities did not change under hypoxia. These findings lead to the hypothesis that SCD-associated metabolic deregulations and a shift to ATP-consuming aberrant γ-glutamyl cycle leads to anemia, dehydration, oxidative stress, and hemolysis driving the biomechanical pathophysiology of erythrocyte of SCD patients. Antioxid. Redox Signal. 42, 199-211.","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"199-211"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603116","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

Nattokinase's Neuroprotective Mechanisms in Ischemic Stroke: Targeting Inflammation, Oxidative Stress, and Coagulation. 纳豆激酶在缺血性中风中的神经保护机制：针对炎症、氧化应激和凝血。

IF 5.9 2区生物学

Antioxidants & redox signaling Pub Date : 2025-02-01 Epub Date: 2024-09-05 DOI: 10.1089/ars.2023.0527

Xin-Ying Yang, Sheng-Lin Wang, Wen-Chi Xue, Yu-Peng Zhang, Liang-Liang Li, Zhao-Hu Luo, Feng-Jiao Zhang

{"title":"Nattokinase's Neuroprotective Mechanisms in Ischemic Stroke: Targeting Inflammation, Oxidative Stress, and Coagulation.","authors":"Xin-Ying Yang, Sheng-Lin Wang, Wen-Chi Xue, Yu-Peng Zhang, Liang-Liang Li, Zhao-Hu Luo, Feng-Jiao Zhang","doi":"10.1089/ars.2023.0527","DOIUrl":"10.1089/ars.2023.0527","url":null,"abstract":"Aims: Nattokinase (NK), a potent serine endopeptidase, has exhibited a variety of pharmacological effects, including thrombolysis, anti-inflammation, and antioxidative stress. Building on previous research highlighting NK's promise in nerve regeneration, our study investigated whether NK exerted protective effects in transient middle cerebral artery occlusion (tMCAO)-induced cerebral ischemia-reperfusion injury and the underlying mechanisms. Results: The rats were administered NK (5000, 10000, 20000 FU/kg, i.g., 7 days before surgery, once daily). We showed that NK treatment dose dependently reduced the infarction volume and improved neurological symptoms, decreased the proinflammatory and coagulation cytokines levels, and attenuated reactive oxygen species (ROS) in the infarcted area of tMCAO rats. We also found that NK could exert neuroprotective effects in a variety of vitro models, including the microglia inflammation model and neuronal oxygen-glucose deprivation/reperfusion (OGD/R) model. Notably, NK effectively countered OGD/R-induced neuron death, modulating diverse pathways, including autophagy, apoptosis, PARP-dependent death, and endoplasmic reticulum stress. Furthermore, the neuroprotection of NK was blocked by phenylmethylsulfonyl fluoride (PMSF), a serine endopeptidase inhibitor. We revealed that heat-inactive NK was unable to protect against tMCAO injury and other vitro models, suggesting NK attenuated ischemic injury by its enzymatic activity. We conducted a proteomic analysis and found inflammation and coagulation were involved in the occurrence of tMCAO model and in the therapeutic effect of NK. Innovation and Conclusion: In conclusion, these data demonstrated that NK had multifaceted neuroprotection in ischemic brain injury, and the therapeutic effect of NK was related with serine endopeptidase activity. Antioxid. Redox Signal. 42, 228-248.","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"228-248"},"PeriodicalIF":5.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970465","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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