Low-input redoxomics facilitates global identification of metabolic regulators of oxidative stress in the gut
Abstract Oxidative stress plays a crucial role in organ aging and related diseases, yet the endogenous regulators involved remain largely unknown. This work highlights the importance of metabolic homeostasis in protecting against oxidative stress in the large intestine. By developing a low-input and...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-01-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-024-02094-7 |
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| author | Xina Xiao Meng Hu Li Gao Huan Yuan Baochen Chong Yu Liu Rou Zhang Yanqiu Gong Dan Du Yong Zhang Hao Yang Xiaohui Liu Yan Zhang Huiyuan Zhang Heng Xu Yi Zhao Wenbo Meng Dan Xie Peng Lei Shiqian Qi Yong Peng Tao Tan Yang Yu Hongbo Hu Biao Dong Lunzhi Dai |
| author_facet | Xina Xiao Meng Hu Li Gao Huan Yuan Baochen Chong Yu Liu Rou Zhang Yanqiu Gong Dan Du Yong Zhang Hao Yang Xiaohui Liu Yan Zhang Huiyuan Zhang Heng Xu Yi Zhao Wenbo Meng Dan Xie Peng Lei Shiqian Qi Yong Peng Tao Tan Yang Yu Hongbo Hu Biao Dong Lunzhi Dai |
| author_sort | Xina Xiao |
| collection | DOAJ |
| description | Abstract Oxidative stress plays a crucial role in organ aging and related diseases, yet the endogenous regulators involved remain largely unknown. This work highlights the importance of metabolic homeostasis in protecting against oxidative stress in the large intestine. By developing a low-input and user-friendly pipeline for the simultaneous profiling of five distinct cysteine (Cys) states, including free SH, total Cys oxidation (Sto), sulfenic acid (SOH), S-nitrosylation (SNO), and S-glutathionylation (SSG), we shed light on Cys redox modification stoichiometries and signaling with regional resolution in the aging gut of monkeys. Notably, the proteins modified by SOH and SSG were associated primarily with cell adhesion. In contrast, SNO-modified proteins were involved in immunity. Interestingly, we observed that the Sto levels ranged from 0.97% to 99.88%, exhibiting two distinct peaks and increasing with age. Crosstalk analysis revealed numerous age-related metabolites potentially involved in modulating oxidative stress and Cys modifications. Notably, we elucidated the role of fumarate in alleviating intestinal oxidative stress in a dextran sulfate sodium (DSS)-induced colitis mouse model. Our findings showed that fumarate treatment promotes the recovery of several cell types, signaling pathways, and genes involved in oxidative stress regulation. Calorie restriction (CR) is a known strategy for alleviating oxidative stress. Two-month CR intervention led to the recovery of many antioxidative metabolites and reshaped the Cys redoxome. This work decodes the complexities of redoxomics during the gut aging of non-human primates and identifies key metabolic regulators of oxidative stress and redox signaling. |
| format | Article |
| id | doaj-art-2a64014054b84848bcac50054cf9113d |
| institution | Kabale University |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-2a64014054b84848bcac50054cf9113d2025-01-12T12:41:40ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-01-0110111810.1038/s41392-024-02094-7Low-input redoxomics facilitates global identification of metabolic regulators of oxidative stress in the gutXina Xiao0Meng Hu1Li Gao2Huan Yuan3Baochen Chong4Yu Liu5Rou Zhang6Yanqiu Gong7Dan Du8Yong Zhang9Hao Yang10Xiaohui Liu11Yan Zhang12Huiyuan Zhang13Heng Xu14Yi Zhao15Wenbo Meng16Dan Xie17Peng Lei18Shiqian Qi19Yong Peng20Tao Tan21Yang Yu22Hongbo Hu23Biao Dong24Lunzhi Dai25National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityAdvanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, NHC Key Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan UniversityAdvanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, NHC Key Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan UniversityAdvanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, NHC Key Lab of Transplant Engineering and Immunology, West China Hospital, Sichuan UniversitySchool of Life Sciences, Tsinghua UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Rheumatology and Immunology, West China Hospital, Sichuan UniversityThe First School of Clinical Medicine, Lanzhou UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and TechnologyBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology and Key Laboratory of Assisted Reproduction, Ministry of Education, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third HospitalNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityNational Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityAbstract Oxidative stress plays a crucial role in organ aging and related diseases, yet the endogenous regulators involved remain largely unknown. This work highlights the importance of metabolic homeostasis in protecting against oxidative stress in the large intestine. By developing a low-input and user-friendly pipeline for the simultaneous profiling of five distinct cysteine (Cys) states, including free SH, total Cys oxidation (Sto), sulfenic acid (SOH), S-nitrosylation (SNO), and S-glutathionylation (SSG), we shed light on Cys redox modification stoichiometries and signaling with regional resolution in the aging gut of monkeys. Notably, the proteins modified by SOH and SSG were associated primarily with cell adhesion. In contrast, SNO-modified proteins were involved in immunity. Interestingly, we observed that the Sto levels ranged from 0.97% to 99.88%, exhibiting two distinct peaks and increasing with age. Crosstalk analysis revealed numerous age-related metabolites potentially involved in modulating oxidative stress and Cys modifications. Notably, we elucidated the role of fumarate in alleviating intestinal oxidative stress in a dextran sulfate sodium (DSS)-induced colitis mouse model. Our findings showed that fumarate treatment promotes the recovery of several cell types, signaling pathways, and genes involved in oxidative stress regulation. Calorie restriction (CR) is a known strategy for alleviating oxidative stress. Two-month CR intervention led to the recovery of many antioxidative metabolites and reshaped the Cys redoxome. This work decodes the complexities of redoxomics during the gut aging of non-human primates and identifies key metabolic regulators of oxidative stress and redox signaling.https://doi.org/10.1038/s41392-024-02094-7 |
| spellingShingle | Xina Xiao Meng Hu Li Gao Huan Yuan Baochen Chong Yu Liu Rou Zhang Yanqiu Gong Dan Du Yong Zhang Hao Yang Xiaohui Liu Yan Zhang Huiyuan Zhang Heng Xu Yi Zhao Wenbo Meng Dan Xie Peng Lei Shiqian Qi Yong Peng Tao Tan Yang Yu Hongbo Hu Biao Dong Lunzhi Dai Low-input redoxomics facilitates global identification of metabolic regulators of oxidative stress in the gut Signal Transduction and Targeted Therapy |
| title | Low-input redoxomics facilitates global identification of metabolic regulators of oxidative stress in the gut |
| title_full | Low-input redoxomics facilitates global identification of metabolic regulators of oxidative stress in the gut |
| title_fullStr | Low-input redoxomics facilitates global identification of metabolic regulators of oxidative stress in the gut |
| title_full_unstemmed | Low-input redoxomics facilitates global identification of metabolic regulators of oxidative stress in the gut |
| title_short | Low-input redoxomics facilitates global identification of metabolic regulators of oxidative stress in the gut |
| title_sort | low input redoxomics facilitates global identification of metabolic regulators of oxidative stress in the gut |
| url | https://doi.org/10.1038/s41392-024-02094-7 |
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