Antioxidants & redox signaling最新文献

{"title":"Epigenetic Control of Redox Pathways in Cancer Progression.","authors":"Vandit Shah, Hiu Yan Lam, Charlene Hoi-Mun Leong, Reo Sakaizawa, Jigna S Shah, Alan Prem Kumar","doi":"10.1089/ars.2023.0465","DOIUrl":"https://doi.org/10.1089/ars.2023.0465","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Growing evidence indicates the importance of redox reactions homeostasis, mediated predominantly by reactive oxygen species (ROS) in influencing the development, differentiation, progression, metastasis, programmed cell death, tumor microenvironment, and therapeutic resistance of cancer. Therefore, reviewing the ROS-linked epigenetic changes in cancer is fundamental to understanding the progression and prevention of cancer. <b><i>Recent Advances:</i></b> We review in depth the molecular mechanisms involved in ROS-mediated epigenetic changes that lead to alteration of gene expression by altering DNA, modifying histones, and remodeling chromatin and noncoding RNA. <b><i>Critical Issues:</i></b> In cancerous cells, alterations of the gene-expression regulatory elements could be generated by the virtue of imbalance in tumor microenvironment. Various oxidizing agents and mitochondrial electron transport chain are the major pathways that generate ROS. ROS plays a key role in carcinogenesis by activating pro-inflammatory signaling pathways and DNA damage. This loss of ROS-mediated epigenetic regulation of the signaling pathways may promote tumorigenesis. We address all such aspects in this review. <b><i>Future Directions:</i></b> Developments in this growing field of epigenetics are expected to contribute to further our understanding of human health and diseases such as cancer and to test the clinical applications of redox-based therapy. Recent studies of the cancer-epigenetic landscape have revealed pervasive deregulation of the epigenetic factors in cancer. Thus, the study of interaction between ROS and epigenetic factors in cancer holds a great promise in the development of effective and targeted treatment modalities. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998902","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":"ALOX15 Aggravates Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice with Type 2 Diabetes via Activating the PPARγ/CD36 Axis.","authors":"Wenhui Yan, Xin Cui, Tingli Guo, Na Liu, Zhuanzhuan Wang, Yuzhuo Sun, Yuanrui Shang, Jieyun Liu, Yuanyuan Zhu, Yangyang Zhang, Lina Chen","doi":"10.1089/ars.2024.0670","DOIUrl":"https://doi.org/10.1089/ars.2024.0670","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent hepatic disorder worldwide. Arachidonic acid 15-lipoxygenase (ALOX15), an enzyme catalyzing the peroxidation of polyunsaturated fatty acids, plays a crucial role in various diseases. Here, we sought to investigate the involvement of ALOX15 in MASLD. <b><i>Results:</i></b> In this study, we observed upregulation of ALOX15 in the liver of high-fat diet (HFD)- and streptozotocin (STZ)-induced mice. Metabolomic analysis revealed elevated levels of ALOX15 metabolites, 12(S)-hydroperoxyeicosatetraenoic acid and 15(S)-hydroperoxyeicosatetraenoic acid. Transcriptomic analysis showed that the increased fatty acid uptake regulated by the PPARγ/CD36 pathway predominated in lipid accumulation. To elucidate the mechanism underlying ALOX15-induced lipid accumulation, HepG2 cells were transfected with a lentivirus expressing ALOX15 or small interfering RNA targeting ALOX15 and exposed to palmitic acid (PA). Both ALOX15 overexpression and PA exposure led to increased intracellular free fatty acid and triglyceride, resulting in lipotoxicity. ALOX15 overexpression aggravated the effect of PA, while the knockdown of ALOX15 attenuated PA-induced lipotoxicity. Moreover, the treatment with PPARγ antagonist GW9662 or CD36 inhibitor sulfosuccinimidyl oleate sodium effectively reduced lipid accumulation and lipotoxicity resulting from ALOX15 overexpression and PA exposure, indicating the involvement of the PPARγ/CD36 pathway in ALOX15-mediated lipid accumulation. Furthermore, liraglutide, a widely used glucagon-like peptide 1 receptor (GLP-1R) agonist (GLP-1RA), improved hepatic lipid accumulation in HFD/STZ-induced mice by suppressing the ALOX15/PPARγ/CD36 pathway. <b><i>Innovation and Conclusion:</i></b> Our study underscores the potential of ALOX15 as an emerging therapeutic target for MASLD. In addition, the GLP-1RA may confer hepatoprotection by regulating ALOX15, enhancing our comprehension of the mechanisms underpinning their protection on MASLD. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998899","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":"The Oxidoreductase Retinol Saturase in Thyroid Gland Is Regulated by Hypothyroidism and Iodide Overload and Its Deletion Impairs Metabolic Homeostasis in Mice.","authors":"Na Yang, Lisa Wessoly, Yueming Meng, Marie F Kiefer, Yingfu Chen, Madita Vahrenbrink, Sascha Wulff, Chen Li, Jonah W Schreier, Julia S Steinhoff, Moritz Oster, Manuela Sommerfeld, Sylvia J Wowro, Konstantin M Petricek, Roberto E Flores, Panos G Ziros, Gerasimos P Sykiotis, Eva K Wirth, Michael Schupp","doi":"10.1089/ars.2023.0458","DOIUrl":"https://doi.org/10.1089/ars.2023.0458","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Thyroid hormones (TH) are major regulators of cell differentiation, growth, and metabolic rate. TH synthesis in the thyroid gland requires high amounts of H₂O₂ to oxidize iodide for the iodination of thyroglobulin (TG). Retinol Saturase (RetSat) is an oxidoreductase implicated in dihydroretinol formation and cellular sensitivity toward peroxides and ferroptosis. RetSat is highly expressed in metabolically active organs where it regulates lipid metabolism and the production of reactive oxygen species. Due to the high expression of RetSat in the thyroid gland and its role in peroxide sensitivity, we investigated the regulation and function of RetSat in the thyroid gland in appropriate mouse models. <b><i>Results:</i></b> RetSat is strongly expressed in thyrocytes, induced by hypothyroidism, and decreased by iodide overload in mice. Thyrocyte-specific deletion of <i>RetSat</i> increased circulating thyroid-stimulating hormone levels, altered thyroid morphology, and disturbed metabolic homeostasis in a diet- and sex-dependent manner without major effects on the concentrations of circulating TH. Moreover, deletion of <i>RetSat</i> increased TG protein levels but lowered TG iodination upon iodide overload. In cultured thyrocytes, acute RetSat depletion altered the expression of genes involved in TH biosynthesis and the response to endoplasmic reticulum stress. <b><i>Innovation:</i></b> This is the first report that specifically dissects the regulation and function of the oxidoreductase RetSat in the thyroid gland. <b><i>Conclusion:</i></b> Deletion of <i>RetSat</i> in thyrocytes induces compensatory feedback mechanisms to maintain TH homeostasis in mice. We conclude that RetSat in the thyroid gland is required for TH biosynthesis and secretion and metabolic homeostasis in mice. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930480","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":"The Emerging Role of Herbal Medicines in Cancer by Interfering with Posttranslational Modifications.","authors":"Rui Wang, Yu Li, Jiahui Ji, Lingwei Kong, Yukai Huang, Zhongqiu Liu, Linlin Lu","doi":"10.1089/ars.2023.0418","DOIUrl":"10.1089/ars.2023.0418","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Herbal medicines have a long history of comprehensive cancer treatment through various posttranslational modifications (PTMs). Recently, emerging evidence revealed that dysregulation of reactive oxygen species (ROS) and ROS-regulated signaling pathways influence cancer initiation, growth, and progression in a paradoxical role with either low levels or increasing levels of basal ROS. However, ROS-triggered modifications of target proteins in the face of ROS-mediated signal transduction are not fully understood in the anticancer therapies of herbal medicines. In this review, we briefly introduce the PTM-dependent regulations of herbal medicines, and then focus on the current ideals that targeting ROS-dependent PTMs <i>via</i> antioxidant and redox signaling pathways can provide a promising strategy in herbal-based anticancer effects. <b><i>Recent Advances:</i></b> Advanced development in highly sensitive mass spectrometry-based techniques has helped utilize ROS-triggered protein modifications in numerous cancers. Accumulating evidence has been achieved in laboratory to extensively ascertain the biological mechanism of herbal medicines targeting ROS in cancer therapy. Two general mechanisms underlining ROS-induced cell signaling include redox state and oxidative modification of target protein, indicating a new perspective to comprehend the intricate dialogues between herbal medicines and cancer cellular contexts. <b><i>Critical Issues:</i></b> Complex components of herbal medicines limit the benefits of herbal-based cancer therapies. In this review, we address that ROS-dependent PTMs add a layer of proteomic complexity to the cancer through altering the protein structure, expression, function, and localization. Elaborating ROS-triggered PTMs implicated in cell signaling, apoptosis, and transcriptional regulation function, and the possible cellular signaling, has provided important information about the contribution of many ROS targeting herbal therapies in anticancer effects. Continued optimization of proteomic strategies for PTM analysis in herbal medicines is also briefly discussed. <b><i>Future Directions:</i></b> Rigorous evaluations of herbal medicines and proteomic strategies are necessary to explore the aberrant regulation of ROS-triggered antioxidant and redox signaling contributing to the novel protein targets and herbal-associated pharmacological issues. These efforts will eventually help develop more herbal drugs as modern therapeutic agents. <i>Antioxid. Redox Signal.</i> 42, 150-164.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"150-164"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544476","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":"Asperuloside as a Novel NRF2 Activator to Ameliorate Endothelial Dysfunction in High Fat Diet-Induced Obese Mice.","authors":"Chufeng He, Ruiwen Zhu, Lei He, Chui Yiu Bamboo Chook, Huixian Li, Fung Ping Leung, Gary Tse, Zhen-Yu Chen, Yu Huang, Wing Tak Wong","doi":"10.1089/ars.2024.0593","DOIUrl":"10.1089/ars.2024.0593","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Current treatments are inadequate in alleviating obesity-associated vascular diseases. The development of effective therapies to ameliorate endothelial dysfunction and attenuate oxidative stress is of utmost importance. Asperuloside (ASP), a bioactive compound extracted from <i>Eucommia species</i>, exhibits antiobesity properties. However, the effects of ASP on vasculopathy have not been investigated. Therefore, the effects of ASP on vascular dysfunction and related mechanisms were elucidated. <b><i>Results:</i></b> ASP significantly reversed the impaired endothelium-dependent relaxations (EDRs) in obese mice and interleukin (IL)-1β-treated aortas. ASP suppressed endothelial activation in obese mice aortas and IL-1β-treated endothelial cells. ASP attenuated oxidative stress, scavenged mitochondrial reactive oxygen species (ROS), and upregulated heme oxygenase-1 (HO-1) expression in endothelium, independent of its anti-inflammatory properties. HO-1 knockdown diminished the protective effects of ASP against impaired EDRs, ROS overproduction, and endothelial activation. Endothelial cell-specific nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown eliminated the ASP-mediated vascular protective effects and endothelial HO-1 upregulation, emphasizing that ASP improves endothelial function by activating Nrf2/HO-1 signaling. ASP facilitated Nrf2 nuclear translocation and the direct binding of Nrf2 to antioxidant response element, thereby enhancing HO-1 transcription and scavenging ROS. The cellular thermal shift assay results provide the first experimental characterization of the direct binding of ASP to Nrf2. <b><i>Conclusions:</i></b> These findings demonstrate that ASP ameliorates obesity-associated endothelial dysfunction by activating Nrf2/HO-1 signaling and thereby maintaining redox hemostasis, suggesting its potential as a novel Nrf2-targeted therapeutic agent and dietary supplement for vasculopathy. <i>Antioxid. Redox Signal.</i> 42, 77-96.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"77-96"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141905678","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":"The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss Through the Nrf2 Pathway.","authors":"Wenji Zhao, Fan Wu, Rui Hu, Jintao Lou, Guisheng Chen, Ziyi Cai, Suijun Chen","doi":"10.1089/ars.2024.0648","DOIUrl":"10.1089/ars.2024.0648","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Cisplatin (CDDP) is a commonly used chemotherapeutic agent for treating head and neck tumors. However, there is high incidence of ototoxicity in patients treated with CDDP, which may be caused by the excessive reactive oxygen species (ROS) generation in the inner ear. Many studies have demonstrated the strong antioxidant effects of ergothioneine (EGT). Therefore, we assumed that EGT could also attenuate cisplatin-induced hearing loss (CIHL) as well. However, the protective effect and mechanism of EGT on CIHL have not been elucidated as so far. In this study, we investigated whether EGT could treat CIHL and the mechanism. <b><i>Results:</i></b> In our study, we confirmed the protective effect of EGT on preventing CDDP-induced toxicity both <i>in vitro</i> and <i>in vivo</i>. The auditory brainstem response threshold shift in the EGT + CDDP treatment mice was 30 dB less than that in the CDDP treatment mice. EGT suppressed production of ROS and proapoptotic proteins both in tissue and cells. By silencing nuclear factor erythroid 2-related factor 2 (Nrf2), we confirmed that EGT protected against CIHL <i>via</i> the Nrf2 pathway. We also found that SLC22A4 (OCTN1), an important molecule involved in transporting EGT, was expressed in the cochlea. <b><i>Innovation:</i></b> Our results revealed the role of EGT in the prevention of CIHL by activating Nrf2/HO-1/NQO-1 pathway, and broadened a new perspective therapeutic target of EGT. <b><i>Conclusion:</i></b> EGT decreased ROS production and promoted the expression of antioxidative enzymes to maintain redox homeostasis in sensory hair cells. Overall, our results indicated that EGT may serve as a novel treatment drug to attenuate CIHL. <i>Antioxid. Redox Signal.</i> 42, 97-114.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"97-114"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070200","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":"Disturbance of Fetal Growth by Azithromycin Through Induction of ER Stress in the Placenta.","authors":"Fan Pan, Fan Zhang, Meng-Die Li, YaKun Liang, Wang-Sheng Wang, Kang Sun","doi":"10.1089/ars.2024.0592","DOIUrl":"10.1089/ars.2024.0592","url":null,"abstract":"<p><p><b><i>Aim:</i></b> Azithromycin (AZM) is widely used to treat mycoplasma infection in pregnancy. However, there is no adequate evaluation of its side effect on the placenta. In this study, using human placental syncytiotrophoblasts and a mouse model, we investigated whether AZM use in pregnancy might adversely affect placental function and pregnancy outcome. <b><i>Results:</i></b> Transcriptomic analysis of AZM-treated human placental syncytiotrophoblasts showed increased expression of endoplasmic reticulum (ER) stress-related genes and decreased expression of genes for hormone production and growth factor processing. Verification studies showed that AZM increased the abundance of ER stress mediators (phosphorylated eIF2α, activating transcription factor 4 [ATF4], and C/EBP Homologous Protein [CHOP]) and decreased the abundance of enzymes involved in progesterone and estradiol synthesis (<i>STS</i>, <i>CYP11A1</i>, and <i>CYP19A1</i>) and insulin-like growth factor binding protein (IGFBP) cleavage (<i>PAPPA</i> and <i>ADAM12</i>) in human placental syncytiotrophoblasts. Inhibition of ER stress blocked AZM-induced decreases in the expression of CYP19A1, CYP11A1, PAPPA, and ADAM12, suggesting that the inhibition of AZM on those genes' expression was secondary to AZM-induced ER stress. Further mechanism study showed that increased ATF4 in ER stress might repressively interact with C/EBPα to suppress the expression of those genes, including <i>CEBPA</i> itself. Mouse studies showed that AZM administration decreased fetal weights along with increased ER stress mediators and decreased levels of insulin-like growth factor, estrogen, and progesterone in the maternal blood, which could be alleviated by inhibition of ER stress. <b><i>Innovation and Conclusion:</i></b> These findings first support the fact that AZM, often used during pregnancy, may affect fetal growth by inhibiting crucial enzymes for estrogen and progesterone synthesis and disrupting crucial proteases for IGFBP cleavage <i>via</i> inducing ER stress in placental syncytiotrophoblasts. <i>Antioxid. Redox Signal.</i> 42, 16-35.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"16-35"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320366","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":"Baicalin Attenuates Diabetic Cardiomyopathy <i>In Vivo</i> and <i>In Vitro</i> by Inhibiting Autophagy and Cell Death Through SENP1/SIRT3 Signaling Pathway Activation.","authors":"Peipei Zhang, Haowei Wu, Haifei Lou, Jiedong Zhou, Jinjin Hao, Hui Lin, Songqing Hu, Zuoquan Zhong, Juntao Yang, Hangyuan Guo, Jufang Chi","doi":"10.1089/ars.2023.0457","DOIUrl":"10.1089/ars.2023.0457","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Diabetic heart damage can lead to cardiomyocyte death, which endangers human health. Baicalin (BAI) is a bioactive compound that plays an important role in cardiovascular diseases. Sentrin/SUMO-specific protease 1 (<i>SENP1</i>) regulates the de-small ubiquitin-like modifier (deSUMOylation) process of Sirtuin 3 (<i>SIRT3</i>) and plays a crucial role in regulating mitochondrial mass and preventing cell injury. Our hypothesis is that BAI regulates the deSUMOylation level of <i>SIRT3</i> through <i>SENP1</i> to enhance mitochondrial quality control and prevent cell death, ultimately improving diabetic cardiomyopathy (DCM). <b><i>Results:</i></b> The protein expression of <i>SENP1</i> decreased in cardiomyocytes induced by high glucose and in db/db mice. The cardioprotective effects of BAI were eliminated by silencing endogenous <i>SENP1</i>, whereas overexpression of <i>SENP1</i> showed similar cardioprotective effects to those of BAI. Furthermore, co-immunoprecipitation experiments showed that BAI's cardioprotective effect was due to the inhibition of the SUMOylation modification level of <i>SIRT3</i> by <i>SENP1</i>. Inhibition of <i>SENP1</i> expression resulted in an increase in SUMOylation of <i>SIRT3</i>. This led to increased acetylation of mitochondrial protein, accumulation of reactive oxygen species, impaired autophagy, impaired mitochondrial oxidative phosphorylation, and increased cell death. None of these changes could be reversed by BAI. <b><i>Conclusion:</i></b> BAI improves DCM by promoting <i>SIRT3</i> deSUMOylation through <i>SENP1</i>, restoring mitochondrial stability, and preventing the cell death of cardiomyocytes. <b><i>Innovation:</i></b> This study proposes for the first time that <i>SIRT3</i> SUMOylation modification is involved in the development of DCM and provides <i>in vivo</i> and <i>in vitro</i> data support that BAI inhibits cardiomyocyte ferroptosis and apoptosis in DCM through <i>SENP1</i>. <i>Antioxid. Redox Signal.</i> 42, 53-76.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"53-76"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140847714","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":"Peroxiredoxin 3 Deficiency Exacerbates DSS-Induced Acute Colitis via Exosomal miR-1260b-Mediated Barrier Disruption and Proinflammatory Signaling.","authors":"Jing Jin, Moajury Jung, Seong-Keun Sonn, Seungwoon Seo, Joowon Suh, Hyae Yon Kweon, Shin Hye Moon, Huiju Jo, Na Hyeon Yoon, Goo Taeg Oh","doi":"10.1089/ars.2023.0482","DOIUrl":"10.1089/ars.2023.0482","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Peroxiredoxin3 (Prdx3) is an intracellular antioxidant enzyme that is specifically localized in mitochondria and protects against oxidative stress by removing mitochondrial reactive oxygen species (ROS). The intestinal epithelium provides a physical and biochemical barrier that segregates host tissues from commensal bacteria to maintain intestinal homeostasis. An imbalance between the cellular antioxidant defense system and oxidative stress has been implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the role of Prdx3 in the intestinal epithelium under intestinal inflammation has not been elucidated. To investigate the potential role of Prdx3 in intestinal inflammation, we used intestinal epithelial cell (IEC)-specific Prdx3-knockout mice. <b><i>Results:</i></b> IEC-specific Prdx3-deficient mice showed more severe colitis phenotypes with greater degrees of body weight loss, colon shortening, barrier disruption, mitochondrial damage, and ROS generation in IECs. Furthermore, exosomal miR-1260b was dramatically increased in Prdx3-knockdown colonic epithelial cells. Mechanistically, Prdx3 deficiency promoted intestinal barrier disruption and inflammation <i>via</i> P38-mitogen-activated protein kinase/NFκB signaling. <b><i>Innovation:</i></b> This is the first study to report the protective role of Prdx3 in acute colitis using IEC-specific conditional knockout mice. <b><i>Conclusion:</i></b> Our study sheds light on the role of exosome-loaded miRNAs, particularly miR-1260b, in IBD. Targeting miR-1260b or modulating exosome-mediated intercellular communication may hold promise as potential therapeutic strategies for managing IBD and restoring intestinal barrier integrity. <i>Antioxid. Redox Signal.</i> 42, 133-149.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"133-149"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544475","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":"CARD11-BCL10-MALT1 Complex-Dependent MALT1 Activation Facilitates Myocardial Oxidative Stress in Doxorubicin-Treated Mice via Enhancing k48-Linked Ubiquitination of Nrf2.","authors":"Li-Qun Lu, Ming-Rui Li, Xu-Yan Liu, Dan Peng, Hong-Rui Liu, Xiao-Jie Zhang, Xiu-Ju Luo, Jun Peng","doi":"10.1089/ars.2023.0543","DOIUrl":"10.1089/ars.2023.0543","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) contributes to doxorubicin (DOX)-induced myocardial oxidative stress, and inhibition of mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) increased Nrf2 protein level in rat heart suffering ischemia/reperfusion, indicating a connection between MALT1 and Nrf2. This study aims to explore the role of MALT1 in DOX-induced myocardial oxidative stress and the underlying mechanisms. <b><i>Results:</i></b> The mice received a single injection of DOX (15 mg/kg, i.p.) to induce myocardial oxidative stress, evidenced by increases in the levels of reactive oxidative species as well as decreases in the activities of antioxidative enzymes, concomitant with a downregulation of Nrf2; these phenomena were reversed by MALT1 inhibitor. Similar phenomena were observed in DOX-induced oxidative stress in cardiomyocytes. Mechanistically, knockdown or inhibition of MALT1 notably attenuated the interaction between Nrf2 and MALT1 and decreased the k48-linked ubiquitination of Nrf2. Furthermore, inhibition or knockdown of calcium/calmodulin-dependent protein kinase II (CaMKII-δ) reduced the phosphorylation of caspase recruitment domain-containing protein 11 (CARD11), subsequently disrupted the assembly of CARD11, B cell lymphoma 10 (BCL10), and MALT1 (CBM) complex, and reduced the MALT1-dependent k48-linked ubiquitination of Nrf2 in DOX-treated mice or cardiomyocytes. <b><i>Innovation and Conclusion:</i></b> The E3 ubiquitin ligase function of MALT1 accounts for the downregulation of Nrf2 and aggravation of myocardial oxidative stress in DOX-treated mice, and CaMKII-δ-dependent phosphorylation of CARD11 triggered the assembly of CBM complex and the subsequent activation of MALT1. <i>Antioxid. Redox Signal.</i> 42, 115-132.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"115-132"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178057","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}