Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis DOI Creative Commons
Hao Zeng,

Naicheng Chen,

Fang Chen

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 3, 2024

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 it fight variety diseases. However, whether provides protection against IR is not fully understood. this study, we revealed that long-term moderate mitigated IR-induced injury by generating carnosine from skeletal muscles. We found exercised mice displayed reduced loss HSC number and function after IR, accompanied alleviated bone marrow damage. Interestingly, these effects were largely abrogated specific deletion synthase Carns1 in contrast, treatment protected HSCs injury. Mechanistically, demonstrated exercise-generated was specifically transported via Slc15a2 then inhibited p53 transcriptional activity directly interacting with its core DNA-binding domain, which led downregulation the target genes p21 Puma, thus promoting proliferation survival inhibiting senescence irradiated HSCs. More importantly, similar role carnosine/Slc15a2-p53 axis observed human cord blood-derived Collectively, our data reveal supplementation may be potential antiradiation strategies.

Language: Английский

Exercise alleviates hematopoietic stem cell injury following radiation via the carnosine/Slc15a2-p53 axis DOI Creative Commons
Hao Zeng,

Naicheng Chen,

Fang Chen

et al.

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 3, 2024

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 it fight variety diseases. However, whether provides protection against IR is not fully understood. this study, we revealed that long-term moderate mitigated IR-induced injury by generating carnosine from skeletal muscles. We found exercised mice displayed reduced loss HSC number and function after IR, accompanied alleviated bone marrow damage. Interestingly, these effects were largely abrogated specific deletion synthase Carns1 in contrast, treatment protected HSCs injury. Mechanistically, demonstrated exercise-generated was specifically transported via Slc15a2 then inhibited p53 transcriptional activity directly interacting with its core DNA-binding domain, which led downregulation the target genes p21 Puma, thus promoting proliferation survival inhibiting senescence irradiated HSCs. More importantly, similar role carnosine/Slc15a2-p53 axis observed human cord blood-derived Collectively, our data reveal supplementation may be potential antiradiation strategies.

Language: Английский

Citations

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