Format

Send to

Choose Destination
Nat Commun. 2019 Jun 10;10(1):2538. doi: 10.1038/s41467-019-10386-8.

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

Author information

1
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University), 400038, Chongqing, China.
2
Department of Toxicology, Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, 550025, Guiyang, China.
3
Institute of Clinical Medicine, Southwest Medical University, 646000, Luzhou, China.
4
College of Basic Medical Sciences, Third Military Medical University, 400038, Chongqing, China.
5
Department of Hematology, Southwest Hospital, Third Military Medical University, 40038, Chongqing, China.
6
Wound Healing and Cell Biology Laboratory, the First Affiliated Hospital, Chinese PLA General Hospital, Trauma Center of Postgraduate Medical College, 100000, Beijing, China. fuxiaobing@vip.sina.com.
7
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Rocket Force Medicine, Third Military Medical University (Army Medical University), 400038, Chongqing, China. shicm@sina.com.

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.

PMID:
31182708
DOI:
10.1038/s41467-019-10386-8

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center