Cordycepin prevents radiation ulcer by inhibiting cell senescence via NRF2 and AMPK in rodents

Ziwen Wang, Zelin Chen, Zhongyong Jiang, Peng Luo, Lang Liu, Yu Huang, Huilan Wang, Yu Wang, Lei Long, Xu Tan, Dengqun Liu, Taotao Jin, Yawei Wang, Yang Wang, Fengying Liao, Chi Zhang, Long Chen, Yibo Gan, Yunsheng Liu, Fan Yang, Chunji Huang, Hongming Miao, Jieping Chen, Tianmin Cheng, Xiaobing Fu () and Chunmeng Shi ()
Additional contact information
Ziwen Wang: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Zelin Chen: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Zhongyong Jiang: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Peng Luo: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Lang Liu: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Yu Huang: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Huilan Wang: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Yu Wang: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Lei Long: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Xu Tan: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Dengqun Liu: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Taotao Jin: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Yawei Wang: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Yang Wang: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Fengying Liao: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Chi Zhang: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Long Chen: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Yibo Gan: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Yunsheng Liu: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Fan Yang: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Chunji Huang: Third Military Medical University
Hongming Miao: Third Military Medical University
Jieping Chen: Third Military Medical University
Tianmin Cheng: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)
Xiaobing Fu: Trauma Center of Postgraduate Medical College
Chunmeng Shi: Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University)

Nature Communications, 2019, vol. 10, issue 1, 1-16

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10386-8

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