2. Academic Validation
  3. Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis

Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis

  • Cell Commun Signal. 2024 Dec 3;22(1):582. doi: 10.1186/s12964-024-01959-2.
Hao Zeng # 1,  Naicheng Chen # 1,  Fang Chen 1,  Xiaoyi Zhong 2,  Lijing Yang 1,  Yukai Lu 1,  Mo Chen 1,  Mingqiang Shen 1,  Song Wang 1,  Shilei Chen 1,  Jia Cao 3,  Xi Zhang 4,  Jinghong Zhao 2,  Yang Xu 1,  Junping Wang 5,  Mengjia Hu 6 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China.
  • 2 Department 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 University, Chongqing, 400037, China.
  • 3 Institute of Toxicology, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China.
  • 4 Medical Center of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
  • 5 State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. wangjunping@tmmu.edu.cn.
  • 6 State Key Laboratory of Trauma and Chemical Poisoning, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. humengjia3260@163.com.
  • 7 Chinese PLA Center for Disease Control and Prevention, Beijing, 100071, China. humengjia3260@163.com.
  • # Contributed equally.
PMID: 39627813 DOI: 10.1186/s12964-024-01959-2
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.

Keywords

Carnosine; Exercise; Hematopoietic stem cell; Radiation; Senescence; p53 activity.

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