Cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents
Identifieur interne : 000926 ( Main/Exploration ); précédent : 000925; suivant : 000927Cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents
Auteurs : Ziwen Wang [République populaire de Chine] ; Zelin Chen [République populaire de Chine] ; Zhongyong Jiang [République populaire de Chine] ; Peng Luo [République populaire de Chine] ; Lang Liu [République populaire de Chine] ; Yu Huang [République populaire de Chine] ; Huilan Wang [République populaire de Chine] ; Yu Wang [République populaire de Chine] ; Lei Long [République populaire de Chine] ; Xu Tan [République populaire de Chine] ; Dengqun Liu [République populaire de Chine] ; Taotao Jin [République populaire de Chine] ; Yawei Wang [République populaire de Chine] ; Yang Wang [République populaire de Chine] ; Fengying Liao [République populaire de Chine] ; Chi Zhang [République populaire de Chine] ; Long Chen [République populaire de Chine] ; Yibo Gan [République populaire de Chine] ; Yunsheng Liu [République populaire de Chine] ; Fan Yang [République populaire de Chine] ; Chunji Huang [République populaire de Chine] ; Hongming Miao [République populaire de Chine] ; Jieping Chen [République populaire de Chine] ; Tianmin Cheng [République populaire de Chine] ; Xiaobing Fu [République populaire de Chine] ; Chunmeng Shi [République populaire de Chine]Source :
- Nature Communications [ 2041-1723 ] ; 2019.
Abstract
The pathological mechanisms of radiation ulcer remain unsolved and there is currently no effective medicine. Here, we demonstrate that persistent DNA damage foci and cell senescence are involved in radiation ulcer development. Further more, we identify cordycepin, a natural nucleoside analogue, as a potent drug to block radiation ulcer (skin, intestine, tongue) in rats/mice by preventing cell senescence through the increase of NRF2 nuclear expression (the assay used is mainly on skin). Finally, cordycepin is also revealed to activate AMPK by binding with the α1 and γ1 subunit near the autoinhibitory domain of AMPK, then promotes p62-dependent autophagic degradation of Keap1, to induce NRF2 dissociate from Keap1 and translocate to the nucleus. Taken together, our findings identify cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents, and activation of AMPK or NRF2 may thus represent therapeutic targets for preventing cell senescence and radiation ulcer.
Url:
DOI: 10.1038/s41467-019-10386-8
PubMed: 31182708
PubMed Central: 6557849
Affiliations:
Links toward previous steps (curation, corpus...)
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- to stream Ncbi, to step Merge: 000690
- to stream Ncbi, to step Curation: 000690
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Le document en format XML
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Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Fan" sort="Yang, Fan" uniqKey="Yang F" first="Fan" last="Yang">Fan Yang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Huang, Chunji" sort="Huang, Chunji" uniqKey="Huang C" first="Chunji" last="Huang">Chunji Huang</name><affiliation wicri:level="1"><nlm:aff 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China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Jieping" sort="Chen, Jieping" uniqKey="Chen J" first="Jieping" last="Chen">Jieping Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>Department of Hematology, Southwest Hospital,</institution><institution>Third Military Medical University,</institution></institution-wrap>40038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>40038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Cheng, Tianmin" sort="Cheng, Tianmin" uniqKey="Cheng T" first="Tianmin" last="Cheng">Tianmin Cheng</name><affiliation wicri:level="1"><nlm:aff 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Chongqing</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">31182708</idno><idno type="pmc">6557849</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557849</idno><idno type="RBID">PMC:6557849</idno><idno type="doi">10.1038/s41467-019-10386-8</idno><date when="2019">2019</date><idno type="wicri:Area/Pmc/Corpus">000142</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000142</idno><idno type="wicri:Area/Pmc/Curation">000142</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000142</idno><idno type="wicri:Area/Pmc/Checkpoint">000864</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000864</idno><idno type="wicri:Area/Ncbi/Merge">000690</idno><idno type="wicri:Area/Ncbi/Curation">000690</idno><idno type="wicri:Area/Ncbi/Checkpoint">000690</idno><idno type="wicri:Area/Main/Merge">000926</idno><idno type="wicri:Area/Main/Curation">000926</idno><idno type="wicri:Area/Main/Exploration">000926</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents</title><author><name sortKey="Wang, Ziwen" sort="Wang, Ziwen" uniqKey="Wang Z" first="Ziwen" last="Wang">Ziwen Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Zelin" sort="Chen, Zelin" uniqKey="Chen Z" first="Zelin" last="Chen">Zelin Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Jiang, Zhongyong" sort="Jiang, Zhongyong" uniqKey="Jiang Z" first="Zhongyong" last="Jiang">Zhongyong Jiang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Luo, Peng" sort="Luo, Peng" uniqKey="Luo P" first="Peng" last="Luo">Peng Luo</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Lang" sort="Liu, Lang" uniqKey="Liu L" first="Lang" last="Liu">Lang Liu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9330 9891</institution-id><institution-id institution-id-type="GRID">grid.413458.f</institution-id><institution>Department of Toxicology, Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education,</institution><institution>Guizhou Medical University,</institution></institution-wrap>550025 Guiyang, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>550025 Guiyang</wicri:regionArea></affiliation></author><author><name sortKey="Huang, Yu" sort="Huang, Yu" uniqKey="Huang Y" first="Yu" last="Huang">Yu Huang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9330 9891</institution-id><institution-id institution-id-type="GRID">grid.413458.f</institution-id><institution>Department of Toxicology, Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education,</institution><institution>Guizhou Medical University,</institution></institution-wrap>550025 Guiyang, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>550025 Guiyang</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Huilan" sort="Wang, Huilan" uniqKey="Wang H" first="Huilan" last="Wang">Huilan Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="GRID">grid.410578.f</institution-id><institution>Institute of Clinical Medicine,</institution><institution>Southwest Medical University,</institution></institution-wrap>646000 Luzhou, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>646000 Luzhou</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yu" sort="Wang, Yu" uniqKey="Wang Y" first="Yu" last="Wang">Yu Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Long, Lei" sort="Long, Lei" uniqKey="Long L" first="Lei" last="Long">Lei Long</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Tan, Xu" sort="Tan, Xu" uniqKey="Tan X" first="Xu" last="Tan">Xu Tan</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Dengqun" sort="Liu, Dengqun" uniqKey="Liu D" first="Dengqun" last="Liu">Dengqun Liu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Jin, Taotao" sort="Jin, Taotao" uniqKey="Jin T" first="Taotao" last="Jin">Taotao Jin</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yawei" sort="Wang, Yawei" uniqKey="Wang Y" first="Yawei" last="Wang">Yawei Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Yang" sort="Wang, Yang" uniqKey="Wang Y" first="Yang" last="Wang">Yang Wang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Liao, Fengying" sort="Liao, Fengying" uniqKey="Liao F" first="Fengying" last="Liao">Fengying Liao</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Chi" sort="Zhang, Chi" uniqKey="Zhang C" first="Chi" last="Zhang">Chi Zhang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Long" sort="Chen, Long" uniqKey="Chen L" first="Long" last="Chen">Long Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Gan, Yibo" sort="Gan, Yibo" uniqKey="Gan Y" first="Yibo" last="Gan">Yibo Gan</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Liu, Yunsheng" sort="Liu, Yunsheng" uniqKey="Liu Y" first="Yunsheng" last="Liu">Yunsheng Liu</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Yang, Fan" sort="Yang, Fan" uniqKey="Yang F" first="Fan" last="Yang">Fan Yang</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Huang, Chunji" sort="Huang, Chunji" uniqKey="Huang C" first="Chunji" last="Huang">Chunji Huang</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>College of Basic Medical Sciences,</institution><institution>Third Military Medical University,</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Miao, Hongming" sort="Miao, Hongming" uniqKey="Miao H" first="Hongming" last="Miao">Hongming Miao</name><affiliation wicri:level="1"><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>College of Basic Medical Sciences,</institution><institution>Third Military Medical University,</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Jieping" sort="Chen, Jieping" uniqKey="Chen J" first="Jieping" last="Chen">Jieping Chen</name><affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>Department of Hematology, Southwest Hospital,</institution><institution>Third Military Medical University,</institution></institution-wrap>40038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>40038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Cheng, Tianmin" sort="Cheng, Tianmin" uniqKey="Cheng T" first="Tianmin" last="Cheng">Tianmin Cheng</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author><author><name sortKey="Fu, Xiaobing" sort="Fu, Xiaobing" uniqKey="Fu X" first="Xiaobing" last="Fu">Xiaobing Fu</name><affiliation wicri:level="1"><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1761 8894</institution-id><institution-id institution-id-type="GRID">grid.414252.4</institution-id><institution>Wound Healing and Cell Biology Laboratory, the First Affiliated Hospital, Chinese PLA General Hospital,</institution><institution>Trauma Center of Postgraduate Medical College,</institution></institution-wrap>100000 Beijing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>100000 Beijing</wicri:regionArea></affiliation></author><author><name sortKey="Shi, Chunmeng" sort="Shi, Chunmeng" uniqKey="Shi C" first="Chunmeng" last="Shi">Chunmeng Shi</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1760 6682</institution-id><institution-id institution-id-type="GRID">grid.410570.7</institution-id><institution>State Key Laboratory of Trauma, Burns and Combined Injury,</institution><institution>Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University),</institution></institution-wrap>400038 Chongqing, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>400038 Chongqing</wicri:regionArea></affiliation></author></analytic><series><title level="j">Nature Communications</title><idno type="eISSN">2041-1723</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">The pathological mechanisms of radiation ulcer remain unsolved and there is currently no effective medicine. Here, we demonstrate that persistent DNA damage foci and cell senescence are involved in radiation ulcer development. Further more, we identify cordycepin, a natural nucleoside analogue, as a potent drug to block radiation ulcer (skin, intestine, tongue) in rats/mice by preventing cell senescence through the increase of NRF2 nuclear expression (the assay used is mainly on skin). Finally, cordycepin is also revealed to activate AMPK by binding with the α1 and γ1 subunit near the autoinhibitory domain of AMPK, then promotes p62-dependent autophagic degradation of Keap1, to induce NRF2 dissociate from Keap1 and translocate to the nucleus. Taken together, our findings identify cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents, and activation of AMPK or NRF2 may thus represent therapeutic targets for preventing cell senescence and radiation ulcer.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Han, G" uniqKey="Han G">G Han</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sonis, St" uniqKey="Sonis S">ST Sonis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vagliano, L" uniqKey="Vagliano L">L Vagliano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Feldmeier, Jj" uniqKey="Feldmeier J">JJ Feldmeier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, Z" uniqKey="Li Z">Z Li</name></author><author><name sortKey="Maitz, P" uniqKey="Maitz P">P 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last="Wang">Ziwen Wang</name></noRegion><name sortKey="Chen, Jieping" sort="Chen, Jieping" uniqKey="Chen J" first="Jieping" last="Chen">Jieping Chen</name><name sortKey="Chen, Long" sort="Chen, Long" uniqKey="Chen L" first="Long" last="Chen">Long Chen</name><name sortKey="Chen, Zelin" sort="Chen, Zelin" uniqKey="Chen Z" first="Zelin" last="Chen">Zelin Chen</name><name sortKey="Cheng, Tianmin" sort="Cheng, Tianmin" uniqKey="Cheng T" first="Tianmin" last="Cheng">Tianmin Cheng</name><name sortKey="Fu, Xiaobing" sort="Fu, Xiaobing" uniqKey="Fu X" first="Xiaobing" last="Fu">Xiaobing Fu</name><name sortKey="Gan, Yibo" sort="Gan, Yibo" uniqKey="Gan Y" first="Yibo" last="Gan">Yibo Gan</name><name sortKey="Huang, Chunji" sort="Huang, Chunji" uniqKey="Huang C" first="Chunji" last="Huang">Chunji Huang</name><name sortKey="Huang, Yu" sort="Huang, Yu" uniqKey="Huang Y" first="Yu" last="Huang">Yu Huang</name><name sortKey="Huang, Yu" sort="Huang, Yu" uniqKey="Huang Y" first="Yu" last="Huang">Yu Huang</name><name sortKey="Jiang, Zhongyong" sort="Jiang, Zhongyong" uniqKey="Jiang Z" first="Zhongyong" last="Jiang">Zhongyong Jiang</name><name sortKey="Jin, Taotao" sort="Jin, Taotao" uniqKey="Jin T" first="Taotao" last="Jin">Taotao Jin</name><name sortKey="Liao, Fengying" sort="Liao, Fengying" uniqKey="Liao F" first="Fengying" last="Liao">Fengying Liao</name><name sortKey="Liu, Dengqun" sort="Liu, Dengqun" uniqKey="Liu D" first="Dengqun" last="Liu">Dengqun Liu</name><name sortKey="Liu, Lang" sort="Liu, Lang" uniqKey="Liu L" first="Lang" last="Liu">Lang Liu</name><name sortKey="Liu, Lang" sort="Liu, Lang" uniqKey="Liu L" first="Lang" last="Liu">Lang Liu</name><name sortKey="Liu, Yunsheng" sort="Liu, Yunsheng" uniqKey="Liu Y" first="Yunsheng" last="Liu">Yunsheng Liu</name><name sortKey="Long, Lei" sort="Long, Lei" uniqKey="Long L" first="Lei" last="Long">Lei Long</name><name sortKey="Luo, Peng" sort="Luo, Peng" uniqKey="Luo P" first="Peng" last="Luo">Peng Luo</name><name sortKey="Miao, Hongming" sort="Miao, Hongming" uniqKey="Miao H" first="Hongming" last="Miao">Hongming Miao</name><name sortKey="Shi, Chunmeng" sort="Shi, Chunmeng" uniqKey="Shi C" first="Chunmeng" last="Shi">Chunmeng Shi</name><name sortKey="Tan, Xu" sort="Tan, Xu" uniqKey="Tan X" first="Xu" last="Tan">Xu Tan</name><name sortKey="Wang, Huilan" sort="Wang, Huilan" uniqKey="Wang H" first="Huilan" last="Wang">Huilan Wang</name><name sortKey="Wang, Huilan" sort="Wang, Huilan" uniqKey="Wang H" first="Huilan" last="Wang">Huilan Wang</name><name sortKey="Wang, Yang" sort="Wang, Yang" uniqKey="Wang Y" first="Yang" last="Wang">Yang Wang</name><name sortKey="Wang, Yawei" sort="Wang, Yawei" uniqKey="Wang Y" first="Yawei" last="Wang">Yawei Wang</name><name sortKey="Wang, Yu" sort="Wang, Yu" uniqKey="Wang Y" first="Yu" last="Wang">Yu Wang</name><name sortKey="Yang, Fan" sort="Yang, Fan" uniqKey="Yang F" first="Fan" last="Yang">Fan Yang</name><name sortKey="Zhang, Chi" sort="Zhang, Chi" uniqKey="Zhang C" first="Chi" last="Zhang">Chi Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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