Resveratrol Rescues Cutaneous Radiation-Induced DNA Damage via a Novel Ampk/SIRT7/HMGB1 Regulatory Axis

Authors

Yi Jin
Xingyuan Liu
Xiaoting Liang
Jiabin Liu
Jieyu Liu
Zonglin Han
Qianxin Lu
Ke Wang
Bingyao Meng
Chunting Zhang
Minna Xu
Jian Guan
Li Ma
Liang Zhou

Publication Date

1-1-2023

Journal

Cell Death & Disease

Abstract

Cutaneous radiation injury (CRI) interrupts the scheduled process of radiotherapy and even compromises the life quality of patients. However, the current clinical options for alleviating CRI are relatively limited. Resveratrol (RSV) has been shown to be a promising protective agent against CRI; yet the mechanisms of RSV enhancing radioresistance were not fully elucidated and limited its clinical application. In this study, we demonstrate RSV promotes cutaneous radioresistance mainly through SIRT7. During ionizing radiation (IR) treatment, RSV indirectly phosphorylates and activates SIRT7 through AMPK, which is critical for maintaining the genome stability of keratinocytes. Immunoprecipitation and mass spectrometry identified HMGB1 to be the key interacting partner of SIRT7 to mediate the radioprotective function of RSV. Mechanistic study elucidated that SIRT7 interacts with and deacetylates HMGB1 to redistribute it into nucleus and "switch on" its function for DNA damage repair. Our findings establish a novel AMPK/SIRT7/HMGB1 regulatory axis that mediates the radioprotective function of RSV to alleviate IR-induced cutaneous DNA injury, providing an efficiently-curative option for patients with CRI during radiotherapy.

Keywords

Humans, Resveratrol, AMP-Activated Protein Kinases, HMGB1 Protein, DNA Damage, Radiation Injuries, Sirtuins

Comments

Supplementary Materials

Data Availability Statement

PMID: 36587031