Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis
Abstract Ionizing radiation (IR) can cause severe dysfunction of hematopoietic stem cells (HSCs), leading to acute or prolonged myelosuppression. In recent years, physical exercise has been recognized as a healthy lifestyle as it can fight a variety of diseases. However, whether it provides protecti...
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BMC
2024-12-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-024-01959-2 |
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| author | Hao Zeng Naicheng Chen Fang Chen Xiaoyi Zhong Lijing Yang Yukai Lu Mo Chen Mingqiang Shen Song Wang Shilei Chen Jia Cao Xi Zhang Jinghong Zhao Yang Xu Junping Wang Mengjia Hu |
| author_facet | Hao Zeng Naicheng Chen Fang Chen Xiaoyi Zhong Lijing Yang Yukai Lu Mo Chen Mingqiang Shen Song Wang Shilei Chen Jia Cao Xi Zhang Jinghong Zhao Yang Xu Junping Wang Mengjia Hu |
| author_sort | Hao Zeng |
| collection | DOAJ |
| description | Abstract Ionizing radiation (IR) can cause severe dysfunction of hematopoietic stem cells (HSCs), leading to acute or prolonged myelosuppression. In recent years, physical exercise has been recognized as a healthy lifestyle as it can fight a variety of diseases. However, whether it provides protection against IR is not fully understood. In this study, we revealed that long-term moderate exercise mitigated IR-induced hematopoietic injury by generating carnosine from skeletal muscles. We found that exercised mice displayed reduced loss of HSC number and function after IR, accompanied by alleviated bone marrow damage. Interestingly, these effects were largely abrogated by specific deletion of carnosine synthase Carns1 in skeletal muscles. In contrast, carnosine treatment protected HSCs against IR-induced injury. Mechanistically, we demonstrated that exercise-generated carnosine was specifically transported to HSCs via Slc15a2 and then inhibited p53 transcriptional activity by directly interacting with its core DNA-binding domain, which led to downregulation of the p53 target genes p21 and Puma, thus promoting the proliferation and survival and inhibiting the senescence of irradiated HSCs. More importantly, a similar role of the carnosine/Slc15a2-p53 axis was observed in human cord blood-derived HSCs. Collectively, our data reveal that moderate exercise or carnosine supplementation may be potential antiradiation strategies. |
| format | Article |
| id | doaj-art-cda75d84bd7b4f2a9c60943380da028e |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-cda75d84bd7b4f2a9c60943380da028e2024-12-08T12:37:59ZengBMCCell Communication and Signaling1478-811X2024-12-0122111610.1186/s12964-024-01959-2Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axisHao Zeng0Naicheng Chen1Fang Chen2Xiaoyi Zhong3Lijing Yang4Yukai Lu5Mo Chen6Mingqiang Shen7Song Wang8Shilei Chen9Jia Cao10Xi Zhang11Jinghong Zhao12Yang Xu13Junping Wang14Mengjia Hu15State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityState Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityState Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityDepartment of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Xinqiao Hospital, Kidney Center of PLA, Third Military Medical UniversityState Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityState Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityState Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityState Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityState Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityState Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityInstitute of Toxicology, College of Preventive Medicine, Third Military Medical UniversityMedical Center of Hematology, Xinqiao Hospital, Third Military Medical UniversityDepartment of Nephrology, the Key Laboratory for the Prevention and Treatment of Chronic Kidney Disease of Chongqing, Xinqiao Hospital, Kidney Center of PLA, Third Military Medical UniversityState Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityState Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityState Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical UniversityAbstract Ionizing radiation (IR) can cause severe dysfunction of hematopoietic stem cells (HSCs), leading to acute or prolonged myelosuppression. In recent years, physical exercise has been recognized as a healthy lifestyle as it can fight a variety of diseases. However, whether it provides protection against IR is not fully understood. In this study, we revealed that long-term moderate exercise mitigated IR-induced hematopoietic injury by generating carnosine from skeletal muscles. We found that exercised mice displayed reduced loss of HSC number and function after IR, accompanied by alleviated bone marrow damage. Interestingly, these effects were largely abrogated by specific deletion of carnosine synthase Carns1 in skeletal muscles. In contrast, carnosine treatment protected HSCs against IR-induced injury. Mechanistically, we demonstrated that exercise-generated carnosine was specifically transported to HSCs via Slc15a2 and then inhibited p53 transcriptional activity by directly interacting with its core DNA-binding domain, which led to downregulation of the p53 target genes p21 and Puma, thus promoting the proliferation and survival and inhibiting the senescence of irradiated HSCs. More importantly, a similar role of the carnosine/Slc15a2-p53 axis was observed in human cord blood-derived HSCs. Collectively, our data reveal that moderate exercise or carnosine supplementation may be potential antiradiation strategies.https://doi.org/10.1186/s12964-024-01959-2Hematopoietic stem cellRadiationExerciseCarnosinep53 activitySenescence |
| spellingShingle | Hao Zeng Naicheng Chen Fang Chen Xiaoyi Zhong Lijing Yang Yukai Lu Mo Chen Mingqiang Shen Song Wang Shilei Chen Jia Cao Xi Zhang Jinghong Zhao Yang Xu Junping Wang Mengjia Hu Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis Cell Communication and Signaling Hematopoietic stem cell Radiation Exercise Carnosine p53 activity Senescence |
| title | Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis |
| title_full | Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis |
| title_fullStr | Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis |
| title_full_unstemmed | Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis |
| title_short | Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis |
| title_sort | exercise alleviates hematopoietic stem cell injury following radiation via the carnosine slc15a2 p53 axis |
| topic | Hematopoietic stem cell Radiation Exercise Carnosine p53 activity Senescence |
| url | https://doi.org/10.1186/s12964-024-01959-2 |
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