Antioxidants & redox signaling最新文献

{"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}

{"title":"Superoxide is an Intrinsic Signaling Molecule Triggering Muscle Hypertrophy.","authors":"Siyu Lu, Yiming Zhou, Mincong Liu, Lijun Gong, Li Liu, Zhigui Duan, Keke Chen, Frank J Gonzalez, Fang Wei, Rong Xiang, Guolin Li","doi":"10.1089/ars.2024.0595","DOIUrl":"10.1089/ars.2024.0595","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Redox signaling plays a key role in skeletal muscle remodeling induced by exercise and prolonged inactivity, but it is unclear which oxidant triggers myofiber hypertrophy due to the lack of strategies to precisely regulate individual oxidants <i>in vivo</i>. In this study, we used tetrathiomolybdate (TM) to dissociate the link between superoxide (O₂^•-) and hydrogen peroxide and thereby to specifically explore the role of O₂^•- in muscle hypertrophy in C2C12 cells and mice. <b><i>Results:</i></b> TM can linearly regulate intracellular O₂^•- levels by inhibition of superoxide dismutase 1 (SOD1). A 70% increase in O₂^•- levels in C2C12 myoblast cells and mice is necessary and sufficient for triggering hypertrophy of differentiated myotubes and can enhance exercise performance by more than 50% in mice. SOD1 knockout blocks TM-induced O₂^•- increments and thereby prevents hypertrophy, whereas SOD1 restoration rescues all these effects. Scavenging O₂^•- with antioxidants abolishes TM-induced hypertrophy and the enhancement of exercise performance, whereas the restoration of O₂^•- levels with a O₂^•- generator promotes muscle hypertrophy independent of SOD1 activity. <b><i>Innovation and Conclusion:</i></b> These findings suggest that O₂^•- is an endogenous initiator of myofiber hypertrophy and that TM may be used to treat muscle wasting diseases. Our work not only suggests a novel druggable mechanism to increase muscle mass but also provides a tool for precisely regulating O₂^•- levels <i>in vivo</i>. <i>Antioxid. Redox Signal.</i> 42, 1-15.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"1-15"},"PeriodicalIF":5.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320367","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":"The Potential of Targeting APE1/Ref-1 as a Therapeutic Intervention for Duchenne Muscular Dystrophy.","authors":"Hannah Lalunio, Nicole Stupka, Craig A Goodman, Alan Hayes","doi":"10.1089/ars.2024.0620","DOIUrl":"https://doi.org/10.1089/ars.2024.0620","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Inflammation and oxidative stress play crucial roles in the development and progression of skeletal muscle diseases. This review aims to examine the existing evidence regarding the involvement and inhibition of APE1/Ref-1 (apurinic/apyrimidinic endonuclease 1/redox factor 1) in diseases, then extrapolate this evidence to the context of skeletal muscle and discuss the potential beneficial effects of APE1/Ref-1 inhibition in ameliorating myopathy with a particular focus on dystrophic pathology. <b><i>Critical Issues:</i></b> Currently, therapeutic interventions targeting pathways, such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor erythroid 2-related factor 2 (NRF2), have shown limited efficacy in both clinical and preclinical settings. Thus, there is a need for a more comprehensive treatment approach. <b><i>Recent Advances:</i></b> APE1/Ref-1 is a multifunctional protein that was initially identified as being involved in DNA repair. However, newer research has revealed its additional role as a redox-sensitive regulator of transcription factors, including NF-κB and NRF2. Numerous studies have reported increased expression of APE1/Ref-1 in various disorders and have demonstrated the beneficial effects of inhibiting its redox function using the small molecular inhibitor, APX3330. Although these pathways are similarly dysregulated in neuromuscular disorders, the specific role of APE1/Ref-1 in skeletal muscle remains unclear, with only a limited number of studies noting its presence in this tissue. <b><i>Future Directions:</i></b> Further studies investigating the role of APE1/Ref-1 in skeletal muscle and identifying whether APE1/Ref-1 is up- or downregulated in dystrophic skeletal muscle would be required to determine whether upregulating or inhibiting the redox function of APE1/Ref-1 will alleviate chronic inflammation and heightened oxidative stress. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891552","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":"Adverse Effects of Nrf2 in Different Organs and the Related Diseases.","authors":"Xuemei Jin, Long Chen, Yuelan Yang, Rongshao Tan, Chunjie Jiang","doi":"10.1089/ars.2024.0586","DOIUrl":"https://doi.org/10.1089/ars.2024.0586","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Under normal physiological conditions, Nrf2 undergoes ubiquitination and subsequent proteasome degradation to maintain its basal activity. Oxidative stress can trigger Nrf2 activation, prompting its translocation to the nucleus where it functions as a transcription factor, activating various antioxidant pathways, and conferring antioxidant properties. <b><i>Recent Advances:</i></b> While extensive research has shown Nrf2's protective role in various diseases, emerging evidence suggests that Nrf2 activation can also produce harmful effects. <b><i>Critical Issues:</i></b> This review examines the pathological contexts in which Nrf2 assumes different roles, emphasizing the mechanisms and conditions that result in adverse outcomes. <b><i>Future Directions:</i></b> Persistent Nrf2 activation may have deleterious consequences, necessitating further investigation into the specific conditions and mechanisms through which Nrf2 exerts its harmful effects. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891543","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":"Nuclear Factor Erythroid 2-Related Factor 2 Activator DDO-1039 Ameliorates Podocyte Injury in Diabetic Kidney Disease via Suppressing Oxidative Stress, Inflammation, and Ferroptosis.","authors":"Xing Liu, Xiuwen Zhai, Xiaoyu Wang, Xiaodong Zhu, Ziyue Wang, Zhengyu Jiang, Hao Bao, ZhaoHong Chen","doi":"10.1089/ars.2024.0653","DOIUrl":"https://doi.org/10.1089/ars.2024.0653","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, and podocyte injury is one of the major contributors to DKD. As a crucial transcriptional factor that regulates cellular response to oxidative stress, nuclear factor erythroid 2-related factor 2 (Nrf2) is an attractive therapeutic target for DKD. In this study, we evaluated the therapeutic potential of DDO-1039, a novel small-molecule Nrf2 activator developed with protein-protein interaction strategy, on podocyte injury in DKD. <b><i>Results:</i></b> DDO-1039 treatment significantly increased Nrf2 protein level and Nrf2 nuclear translocation, thereby upregulating Nrf2 target genes [heme oxygenase 1, NAD(P)H quinone dehydrogenase 1, glutamate-cysteine ligase modifier, and tyrosine-protein kinase receptor] both <i>in vitro</i> and <i>in vivo</i>. DDO-1039 attenuated glomerular sclerosis and podocyte injury in the high-fat diet/streptozotocin-induced (HFD/STZ) diabetic mice and db/db diabetic mice. It also significantly improved hyperglycemia in both diabetic mice and mitigated proteinuria in HFD/STZ mice. Meanwhile, DDO-1039 attenuated oxidative stress and inflammation as well as apoptosis <i>in vivo</i> and in podocytes stimulated with palmitic acid and high glucose. Interestingly, we identified podocyte protective factor Tyro3 as a novel Nrf2-regulated gene. In addition, podocyte ferroptosis is reduced <i>via</i> activation of glutathione peroxidase 4 by the novel Nrf2 activator. <b><i>Innovation and conclusion:</i></b> DDO-1039 activates the Nrf2-based cytoprotective system to mitigate podocyte injury in the context of diabetes, suggesting the potential of DDO-1039 in the treatment of DKD. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891547","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":"Anti-Inflammatory Effects of Hydrogen Sulfide in Axes Between Gut and Other Organs.","authors":"Weizhuo Lu, Jiyue Wen","doi":"10.1089/ars.2023.0531","DOIUrl":"https://doi.org/10.1089/ars.2023.0531","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Hydrogen sulfide (H₂S), a ubiquitous small gaseous signaling molecule, plays a critical role in various diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA), ischemic stroke, and myocardial infarction (MI) <i>via</i> reducing inflammation, inhibiting oxidative stress, and cell apoptosis. <b><i>Recent Advances:</i></b> Uncontrolled inflammation is closely related to pathological process of ischemic stroke, RA, MI, and IBD. Solid evidence has revealed the axes between gut and other organs like joint, brain, and heart, and indicated that H₂S-mediated anti-inflammatory effect against IBD, RA, MI, and ischemic stroke might be related to regulating the functions of axes between gut and other organs. <b><i>Critical Issues:</i></b> We reviewed endogenous H₂S biogenesis and the H₂S-releasing donors, and revealed the anti-inflammatory effects of H₂S in IBD, ischemic stroke, RA, and MI. Importantly, this review outlined the potential role of H₂S in the gut-joint axis, gut-brain axis, and gut-heart axis as a gasotransmitter. <b><i>Future Direction:</i></b> The rate, location, and timing of H₂S release from its donors determine its potential success or failure as a useful therapeutic agent and should be focused on in the future research. Therefore, there is still a need to explore internal and external sources monitoring and controlling H₂S concentration. Moreover, more efficient H₂S-releasing compounds are needed; a better understanding of their chemistry and properties should be further developed. <i>Antioxid. Redox Signal.</i> 00, 000-000.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142798974","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}