Redox Biology最新文献

{"title":"Redox-dependent purine degradation triggers postnatal loss of cardiac regeneration potential","authors":"Yuichi Saito ,&nbsp;Yuki Sugiura ,&nbsp;Akane Sakaguchi ,&nbsp;Tai Sada ,&nbsp;Chihiro Nishiyama ,&nbsp;Rae Maeda ,&nbsp;Mari Kaneko ,&nbsp;Hiroshi Kiyonari ,&nbsp;Wataru Kimura","doi":"10.1016/j.redox.2024.103442","DOIUrl":"10.1016/j.redox.2024.103442","url":null,"abstract":"<div><div>Postnatal cardiomyocyte cell cycle withdrawal is a critical step wherein the mammalian heart loses regenerative potential after birth. Here, we conducted interspecies multi-omic comparisons between the mouse heart and that of the opossum, which have different postnatal time-windows for cardiomyocyte cell cycle withdrawal. Xanthine metabolism was activated in both postnatal hearts in parallel with cardiomyocyte cell cycle arrest. The pentose phosphate pathway (PPP) which produces NADPH was found to decrease simultaneously. Postnatal myocardial tissues became oxidized accordingly, and administration of antioxidants to neonatal mice altered the PPP and suppressed the postnatal activation of cardiac xanthine metabolism. These results suggest a redox-driven postnatal switch from purine synthesis to degradation in the heart. Importantly, inhibition of xanthine metabolism in the postnatal heart extended postnatal duration of cardiomyocyte proliferation and maintained postnatal heart regeneration potential in mice. These findings highlight a novel role of xanthine metabolism as a redox-dependent metabolic regulator of cardiac regeneration potential.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103442"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coupling of mitochondrial state with active zone plasticity in early brain aging","authors":"Lu Fei ,&nbsp;Yongtian Liang ,&nbsp;Ulrich Kintscher ,&nbsp;Stephan J. Sigrist","doi":"10.1016/j.redox.2024.103454","DOIUrl":"10.1016/j.redox.2024.103454","url":null,"abstract":"<div><div>Neurodegenerative diseases typically emerge after an extended prodromal period, underscoring the critical importance of initiating interventions during the early stages of brain aging to enhance later resilience. Changes in presynaptic active zone proteins (\"PreScale\") are considered a dynamic, resilience-enhancing form of plasticity in the process of early, still reversible aging of the Drosophila brain. Aging, however, triggers significant changes not only of synapses but also mitochondria. While the two organelles are spaced in close proximity, likely reflecting a direct functional coupling in regard to ATP and Ca²⁺ homeostasis, the exact modes of coupling in the aging process remain to understood.</div><div>We here show that genetic manipulations of mitochondrial functional status, which alters brain oxidative phosphorylation, ATP levels, or the production of reactive oxygen species (ROS), can bidirectionally regulate PreScale during early Drosophila brain aging. Conversely, genetic mimicry of PreScale resulted in decreased oxidative phosphorylation and ATP production, potentially due to reduced mitochondrial calcium (Ca²⁺) import.</div><div>Our findings indicate the existence of a positive feedback loop where mitochondrial functional state and PreScale are reciprocally coupled to optimize protection during the early stages of brain aging.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103454"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomic 8-oxoguanine modulates gene transcription independent of its repair by DNA glycosylases OGG1 and MUTYH","authors":"Tobias Obermann ,&nbsp;Teri Sakshaug ,&nbsp;Vishnu Vignesh Kanagaraj ,&nbsp;Andreas Abentung ,&nbsp;Mirta Mittelstedt Leal de Sousa ,&nbsp;Lars Hagen ,&nbsp;Antonio Sarno ,&nbsp;Magnar Bjørås ,&nbsp;Katja Scheffler","doi":"10.1016/j.redox.2024.103461","DOIUrl":"10.1016/j.redox.2024.103461","url":null,"abstract":"<div><div>8-oxo-7,8-dihydroguanine (OG) is one of the most abundant oxidative lesions in the genome and is associated with genome instability. Its mutagenic potential is counteracted by a concerted action of 8-oxoguanine DNA glycosylase (OGG1) and mutY homolog DNA glycosylase (MUTYH). It has been suggested that OG and its repair has epigenetic-like properties and mediates transcription, but genome-wide evidence of this interdependence is lacking. Here, we applied an improved OG-sequencing approach reducing artificial background oxidation and RNA-sequencing to correlate genome-wide distribution of OG with gene transcription in OGG1 and/or MUTYH-deficient cells. Our data identified moderate enrichment of OG in the genome that is mainly dependent on the genomic context and not affected by DNA glycosylase-initiated repair. Interestingly, no association was found between genomic OG deposition and gene expression changes upon loss of OGG1 and MUTYH. Regardless of DNA glycosylase activity, OG in promoter regions correlated with expression of genes related to metabolic processes and damage response pathways indicating that OG functions as a cellular stress sensor to regulate transcription. Our work provides novel insights into the mechanism underlying transcriptional regulation by OG and DNA glycosylases OGG1 and MUTYH and suggests that oxidative DNA damage accumulation and its repair utilize different pathways.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103461"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142814124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial ROS modulate presynaptic plasticity in the drosophila neuromuscular junction","authors":"Irina Stavrovskaya,&nbsp;Bethany Kristi Morin,&nbsp;Stephen Madamba,&nbsp;Cliyahnelle Alexander,&nbsp;Alexis Romano,&nbsp;Samia Alam,&nbsp;Lucas Pavlov,&nbsp;Erna Mitaishvili,&nbsp;Pablo M. Peixoto","doi":"10.1016/j.redox.2024.103474","DOIUrl":"10.1016/j.redox.2024.103474","url":null,"abstract":"<div><div>The elevated emission of reactive oxygen species (ROS) from presynaptic mitochondria is well-documented in several inflammatory and neurodegenerative diseases. However, the potential role of mitochondrial ROS in presynaptic function and plasticity remains largely understudied beyond the context of disease. Here, we investigated this potential ROS role in presynaptic function and short-term plasticity by combining optogenetics, whole cell electrophysiological recordings, and live confocal imaging using a well-established protocol for induction and measurement of synaptic potentiation in <em>Drosophila melanogaster</em> neuromuscular junctions (NMJ). Optogenetic induction of ROS emission from presynaptic motorneuron mitochondria expressing mitokiller red (mK) resulted in synaptic potentiation, evidenced by an increase in the frequency of spontaneous mini excitatory junction potentials. Notably, this effect was not observed in flies co-expressing catalase, a cytosolic hydrogen peroxide (H₂O₂) scavenging enzyme. Moreover, the increase in electrical activity did not coincide with synaptic structural changes. The absence of Wnt1/Wg release from synaptic boutons suggested involvement of alternative or non-canonical signaling pathway(s). However, in existing boutons we observed an increase in the active zone (AZ) marker Brp/Erc1, which serves as docking site for the neurotransmitter vesicle release pool. We propose the involvement of putative redox switches in AZ components as the molecular target of mitochondrial H₂O₂. These findings establish a novel framework for understanding the signaling role of mROS in presynaptic structural and functional plasticity, providing insights into redox-based mechanisms of neuronal communication.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103474"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic potential of monomethyl fumarate and aluminum ion combination in alleviating inflammation and oxidative stress in psoriasis","authors":"Hang Han ,&nbsp;Guojiang Zhang ,&nbsp;Yuanyuan Yang ,&nbsp;Chenxi Li ,&nbsp;Xiandeng Li ,&nbsp;Ling Zhong ,&nbsp;Zan Chen ,&nbsp;Jianxia Xiong ,&nbsp;Tao Cai ,&nbsp;Lingjuan Zhang ,&nbsp;Xiao Zhang ,&nbsp;Qinjian Zhao","doi":"10.1016/j.redox.2024.103482","DOIUrl":"10.1016/j.redox.2024.103482","url":null,"abstract":"<div><div>Psoriasis is a chronic inflammatory skin condition characterized by erythematous plaques with white scales. Its pathogenesis is closely linked to oxidative stress and an imbalance in Th1/Th2 immune responses. Current treatments for psoriasis, such as topical agents, systemic therapies and phototherapy, frequently fail to achieve complete remission in clinical settings. Monomethyl fumarate (MMF), which has been approved by the US Food and Drug Administration in 2020 for multiple sclerosis, has demonstrated efficacy in psoriasis management. Additionally, our previous studies have identified aluminum ions as beneficial in psoriasis treatment. This present study investigates the combined therapeutic effects of MMF and aluminum ions and observed that the combination treatment achieves superior efficacy compared to either treatment alone in a psoriasis mouse model through the modulation of the Nrf2/NF-κB signaling pathway, as demonstrated in cellular models. The combination first activates Nrf2 nuclear translocation and induces antioxidant gene expression, followed by the inhibition of NF-κB nuclear translocation and phosphorylation, which reduces Th1 cytokine production and cellular chemotaxis. Concurrently, the treatment elevates Th2 cytokine secretion, thereby increasing the anti-inflammatory response in HaCaT cells. Overall, these findings support the MMF and aluminum ions combination (MMFAL) as a potential therapeutic strategy for psoriasis, effectively diminishing inflammation and oxidative stress.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103482"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiomyocyte-specific Piezo1 deficiency mitigates ischemia-reperfusion injury by preserving mitochondrial homeostasis","authors":"Honglin Xu ,&nbsp;Xin Chen ,&nbsp;Shangfei Luo ,&nbsp;Jintao Jiang ,&nbsp;Xianmei Pan ,&nbsp;Yu He ,&nbsp;Bo Deng ,&nbsp;Silin Liu ,&nbsp;Rentao Wan ,&nbsp;Liwen Lin ,&nbsp;Qiaorui Tan ,&nbsp;Xiaoting Chen ,&nbsp;Youfen Yao ,&nbsp;Bin He ,&nbsp;Yajuan An ,&nbsp;Jing Li","doi":"10.1016/j.redox.2024.103471","DOIUrl":"10.1016/j.redox.2024.103471","url":null,"abstract":"<div><div>Ca²⁺ overload and mitochondrial dysfunction play crucial roles in myocardial ischemia-reperfusion (I/R) injury. Piezo1, a mechanosensitive cation channel, is essential for intracellular Ca²⁺ homeostasis. The objective of this research was to explore the effects of Piezo1 on mitochondrial function during myocardial I/R injury. We showed that the expression of myocardial Piezo1 was elevated in the infracted area of I/R and cardiomyocyte-specific <em>Piezo1</em> deficiency (<em>Piezo1</em>^{<em>△Myh6</em>}) mice attenuated I/R by decreasing infarct size and cardiac dysfunction. <em>Piezo1</em>^{<em>△Myh6</em>} regulated mitochondrial fusion and fission to improve mitochondrial function and decrease inflammation and oxidative stress <em>in vivo</em> and in vitro. Mechanistically, myocardial Piezo1 knockout alleviated intracellular calcium overload to normalize calpain-associated mitochondrial homeostasis. Our findings indicated that Piezo1 depletion in cardiomyocytes partially restored mitochondrial homeostasis during cardiac ischemia/reperfusion (I/R) injury. This study suggests an innovative therapeutic strategy to alleviate cardiac I/R injury.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103471"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142910419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting p62 by sulforaphane promotes autolysosomal degradation of SLC7A11, inducing ferroptosis for osteosarcoma treatment","authors":"Qiuming Zou ,&nbsp;Xiaofeng Zhou ,&nbsp;Jianqin Lai ,&nbsp;Haixia Zhou ,&nbsp;Jinxuan Su ,&nbsp;Zhijing Zhang ,&nbsp;Xiaosong Zhuang ,&nbsp;Lili Liu ,&nbsp;Ruijie Yuan ,&nbsp;Sijia Li ,&nbsp;Siyu Yang ,&nbsp;Xinyi Qu ,&nbsp;Jiezhu Feng ,&nbsp;Yongqi Liu ,&nbsp;Zisheng Li ,&nbsp;Shiting Huang ,&nbsp;Zhi Shi ,&nbsp;Yu Yan ,&nbsp;Zhiming Zheng ,&nbsp;Wencai Ye ,&nbsp;Qi Qi","doi":"10.1016/j.redox.2024.103460","DOIUrl":"10.1016/j.redox.2024.103460","url":null,"abstract":"<div><div>Osteosarcoma (OS) is the most prevalent malignant bone tumor in children and adolescents worldwide. Identification of novel therapeutic targets and development of targeted drugs are one of the most feasible strategies for OS treatment. Ferroptosis, a recently discovered mode of programmed cell death, has been implicated as a potential strategy for cancer therapy. Sulforaphane (SFN), the main bioactive compound derived from cruciferous vegetables, has shown potential anti-cancer effects with negligible toxicity. However, the role of ferroptosis in the effect of SFN on OS remains unknown. In the present study, we found that SFN acted as a potent ferroptosis inducer in OS, which was demonstrated by various inhibitors of cell death. The SFN-induced ferroptotic cell death was characterized by elevated ROS levels, lipid peroxidation, and GSH depletion, which was dependent on decreased levels of SLC7A11. Mechanically, SFN directly targeted p62 protein and enhanced p62/SLC7A11 protein-protein interaction, thereby promoting the lysosomal degradation of SLC7A11 and triggering ferroptosis. Notably, both subcutaneous and intratibial OS models in nude mice confirmed the ferroptosis associated anti-cancer efficacy of SFN <em>in vivo</em>. Hence, our findings demonstrate that SFN exerts its anti-cancer effects through inducing SLC7A11-dependent ferroptosis in OS, providing compelling evidence for the application of SFN in OS treatment.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103460"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac secreted HSP90α exacerbates pressure overload myocardial hypertrophy and heart failure","authors":"Le Pan ,&nbsp;Chenxing Huang ,&nbsp;Xuejuan Jin ,&nbsp;Jian Wu ,&nbsp;Kejia Jin ,&nbsp;Jingyi Lin ,&nbsp;Ying Wang ,&nbsp;Jianxuan Li ,&nbsp;Chao Yin ,&nbsp;Xiang Wang ,&nbsp;Lei Zhang ,&nbsp;Guoping Zhang ,&nbsp;Hangming Dong ,&nbsp;Junli Guo ,&nbsp;Issei Komuro ,&nbsp;Yuxiang Dai ,&nbsp;Yunzeng Zou ,&nbsp;Hui Gong","doi":"10.1016/j.redox.2024.103466","DOIUrl":"10.1016/j.redox.2024.103466","url":null,"abstract":"<div><div>Sustained myocardial hypertrophy or left ventricular hypertrophy (LVH) triggered by pressure overload is strongly linked to adverse cardiovascular outcomes. Here, we investigated the clinical relationship between serum HSP90α (an isoform of HSP90) levels and LVH in patients with hypertension or aortic stenosis (AS) and explored underlying mechanisms in pressure overload mouse model. We built a pressure overload mouse model via transverse aortic constriction (TAC). Compared to controls, elevated <strong>s</strong>erum HSP90α levels were observed in patients with hypertension or AS, and the levels positively correlated with LVH. Similarly, HSP90α levels increased in heart tissues from patients with obstructive hypertrophic cardiomyopathy (HCM), and in mice post-TAC. TAC induced the enhanced cardiac expression and secretion of HSP90α from cardiomyocytes and cardiac fibroblasts. Knockdown of HSP90α or blockade of extracellular HSP90α (eHSP90α) attenuated cardiac hypertrophy and dysfunction by inhibition of β-catenin/TCF7 signaling under pressure overload. Further analysis revealed that eHSP90α interacted with EC1-EC2 region of N-cadherin to activate β-catenin, enhancing the transcription of hypertrophic genes by TCF7, resulting in cardiac hypertrophy and dysfunction under pressure overload. These insights suggest the therapeutic potential of targeting HSP90α-initiated signaling pathway against cardiac hypertrophy and heart failure under pressure overload.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103466"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142897158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning and SHAP value interpretation for predicting comorbidity of cardiovascular disease and cancer with dietary antioxidants","authors":"Xiangjun Qi ,&nbsp;Shujing Wang ,&nbsp;Caishan Fang ,&nbsp;Jie Jia ,&nbsp;Lizhu Lin ,&nbsp;Tianhui Yuan","doi":"10.1016/j.redox.2024.103470","DOIUrl":"10.1016/j.redox.2024.103470","url":null,"abstract":"<div><h3>Objective</h3><div>To develop and validate a machine learning model incorporating dietary antioxidants to predict cardiovascular disease (CVD)-cancer comorbidity and to elucidate the role of antioxidants in disease prediction.</div></div><div><h3>Methods</h3><div>Data were sourced from the National Health and Nutrition Examination Survey. Antioxidants, including vitamins, minerals, and polyphenols, were selected as key features. Additionally, demographic, lifestyle, and health condition features were incorporated to improve model accuracy. Feature preprocessing included removing collinear features, addressing class imbalance, and normalizing data. Models constructed within the mlr3 framework included recursive partitioning and regression trees, random forest, kernel k-nearest neighbors, naïve bayes, and light gradient boosting machine (LightGBM). Benchmarking provided a systematic approach to evaluating and comparing model performance. SHapley Additive exPlanation (SHAP) values were calculated to determine the prediction role of each feature in the model with the highest predictive performance.</div></div><div><h3>Results</h3><div>This analysis included 10,064 participants, with 353 identified as having comorbid CVD and cancer. After excluding collinear features, the machine learning model retained 29 dietary antioxidant features and 9 baseline features. LightGBM achieved the highest predictive accuracy at 87.9 %, a classification error rate of 12.1 %, and the top area under the receiver operating characteristic curve (0.951) and the precision‐recall curve (0.930). LightGBM also demonstrated balanced sensitivity and specificity, both close to 88 %. SHAP analysis indicated that naringenin, magnesium, theaflavin, kaempferol, hesperetin, selenium, malvidin, and vitamin C were the most influential contributors.</div></div><div><h3>Conclusion</h3><div>LightGBM exhibited the best performance for predicting CVD-cancer comorbidity. SHAP values highlighted the importance of antioxidants, with naringenin and magnesium emerging as primary factors in this model.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103470"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular hydrogen reduces dermatitis-induced itch, diabetic itch and cholestatic itch by inhibiting spinal oxidative stress and synaptic plasticity via SIRT1-β-catenin pathway in mice","authors":"Linlin Zhang ,&nbsp;Fangshi Zhao ,&nbsp;Yize Li ,&nbsp;Zhenhua Song ,&nbsp;Lingyue Hu ,&nbsp;Yuanjie Li ,&nbsp;Rui Zhang ,&nbsp;Yonghao Yu ,&nbsp;Guolin Wang ,&nbsp;Chunyan Wang","doi":"10.1016/j.redox.2024.103472","DOIUrl":"10.1016/j.redox.2024.103472","url":null,"abstract":"<div><div>Chronic itch which is primarily associated with dermatologic, systemic, or metabolic disorders is often refractory to most current antipruritic medications, thus highlighting the need for improved therapies. Oxidative damage is a novel determinant of spinal pruriceptive sensitization and synaptic plasticity. The resolution of oxidative insult by molecular hydrogen has been manifested. Herein, we strikingly report that both hydrogen gas (2 %) inhalation and hydrogen-rich saline (5 mL/kg, intraperitoneal) injection prevent and alleviate persistent dermatitis-induced itch, diabetic itch and cholestatic itch. Hydrogen therapy reverses the decrease of spinal SIRT1 expression and antioxidant enzymes (SOD, GPx and CAT) activity after dermatitis, diabetes and cholestasis. Furthermore, hydrogen reduces spinal ROS generation, oxidation products (MDA, 8-OHdG and 3-NT) accumulation, β-catenin acetylation and dendritic spine density in persistent itch models. Spinal SIRT1 inhibition eliminates antipruritic and antioxidative effects of hydrogen, while SIRT1 agonism attenuates chronic itch phenotype, spinal β-catenin acetylation and mitochondrial damage. β-catenin inhibitors are effective against chronic itch via reducing β-catenin acetylation, blocking ERK phosphorylation and elevating antioxidant enzymes activity. Hydrogen treatment suppressed dermatitis and cholestasis mediated spontaneous excitatory postsynaptic currents <em>in vit</em>ro. Additionally, hydrogen impairs cholestasis-induced the enhancement of cerebral functional connectivity between the right primary cingulate cortex and bilateral sensorimotor cortex, as well as bilateral striatum. Taken together, this study uncovers that molecular hydrogen protects against chronic pruritus and spinal pruriceptive sensitization by reducing oxidative damage via up-regulation of SIRT1-dependent β-catenin deacetylation in mice, implying a promising strategy in translational development for itch control.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"79 ","pages":"Article 103472"},"PeriodicalIF":10.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}