PMID- 33912959 OWN - NLM STAT- MEDLINE DCOM- 20211222 LR - 20211222 IS - 1349-9157 (Electronic) IS - 0449-3060 (Print) IS - 0449-3060 (Linking) VI - 62 IP - 4 DP - 2021 Jul 10 TI - Resveratrol protects intestinal epithelial cells against radiation-induced damage by promoting autophagy and inhibiting apoptosis through SIRT1 activation. PG - 574-581 LID - 10.1093/jrr/rrab035 [doi] AB - Intrinsic autophagy is important for the maintenance of intestinal homeostasis and intestinal regeneration. Ionizing radiation suppresses intrinsic autophagy and reduces damage-induced regeneration in the intestine, resulting in intestinal injury. Resveratrol, a sirtuin 1 (SIRT1) agonist, promotes autophagy and exerts radioprotective effect. In this study, the protective effect of resveratrol against radiation-induced intestinal injury and its potential mechanism were investigated. Intestinal epithelial cells (IEC-6) were exposed to 10 Gy ionizing radiation and resveratrol (0.1-40.0 muM). Cell viability was investigated using Cell Counting Kit 8 (CCK8), apoptosis was observed by Annexin V-fluorescein isothiocyanate/propidium iodide (PI) staining and flow cytometry, and the expression of apoptotic and autophagic proteins was determined by western blotting. Resveratrol exerted a high toxicity against IEC-6 cells, but at low concentrations, it inhibited ionizing radiation-induced apoptosis. Resveratrol increased SIRT1 expression after irradiation and inhibited ionizing radiation-induced p53 acetylation and pro-apoptotic protein, Bax, expression. Furthermore, resveratrol promoted autophagy via the phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway, thereby protecting IEC-6 cells against radiation-induced damage. These results suggest that resveratrol reduces radiation-induced IEC-6 cell damage by inhibiting apoptosis and promoting autophagy via the activation of SIRT1, and that the PI3K/AKT/mTOR signaling pathway is involved in the induction of autophagy. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. FAU - Qin, Haoren AU - Qin H AD - Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. FAU - Zhang, Heng AU - Zhang H AD - Tianjin Union Medical Center of Nankai University, Department of Oncology, Tianjin 300121, China. FAU - Zhang, Xipeng AU - Zhang X AD - Tianjin Union Medical Center of Nankai University, Department of Colorectal Surgery, Tianjin 300121, China. FAU - Zhang, Shiwu AU - Zhang S AD - Tianjin Union Medical Center of Nankai University, Department of Pathology, Tianjin 300121, China. FAU - Zhu, Siwei AU - Zhu S AD - Tianjin Union Medical Center of Nankai University, Department of Oncology, Tianjin 300121, China. FAU - Wang, Hui AU - Wang H AD - Tianjin Union Medical Center of Nankai University, Department of Oncology, Tianjin 300121, China. LA - eng GR - 81972847/National Natural Science Foundation of China/ PT - Journal Article PL - England TA - J Radiat Res JT - Journal of radiation research JID - 0376611 RN - 0 (Beclin-1) RN - 0 (Map1lc3b protein, mouse) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.5.1.- (Sirtuin 1) RN - Q369O8926L (Resveratrol) SB - IM MH - Acetylation/drug effects/radiation effects MH - Animals MH - *Apoptosis/drug effects/radiation effects MH - *Autophagy/drug effects/radiation effects MH - Beclin-1/metabolism MH - Cell Line MH - Cell Survival/drug effects/radiation effects MH - *Cytoprotection/drug effects/radiation effects MH - Enterocytes/drug effects/*pathology/radiation effects MH - Mice MH - Microtubule-Associated Proteins/metabolism MH - Models, Biological MH - *Radiation, Ionizing MH - Resveratrol/*pharmacology MH - Signal Transduction/drug effects MH - Sirtuin 1/*metabolism MH - TOR Serine-Threonine Kinases/metabolism MH - Tumor Suppressor Protein p53/metabolism PMC - PMC8273810 OTO - NOTNLM OT - autophagy OT - ionizing radiation OT - radiation protection OT - resveratrol OT - sirtuin 1 (SIRT1) EDAT- 2021/04/30 06:00 MHDA- 2021/12/24 06:00 PMCR- 2021/04/29 CRDT- 2021/04/29 06:37 PHST- 2020/09/22 00:00 [received] PHST- 2021/01/02 00:00 [revised] PHST- 2021/04/30 06:00 [pubmed] PHST- 2021/12/24 06:00 [medline] PHST- 2021/04/29 06:37 [entrez] PHST- 2021/04/29 00:00 [pmc-release] AID - 6257739 [pii] AID - rrab035 [pii] AID - 10.1093/jrr/rrab035 [doi] PST - ppublish SO - J Radiat Res. 2021 Jul 10;62(4):574-581. doi: 10.1093/jrr/rrab035.