Abstract

Lipid peroxidation-induced ferroptosis is a newly recognized type of programmed cell death. With the method of RNA sequencing, we found that irradiation (IR) markedly increased the expression of ferroptosis promotive genes, whereas reduced the expression of ferroptosis suppressive genes in murine intestine tissues, when compared with those of liver and lung tissues. By using ferroptosis inducer RSL-3 and inhibitor liproxstatin-1, we found that ferroptosis is essential for IR-induced intestinal injury. Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) is an important component for ferroptosis execution, and we found that ACSL4 expression was significantly upregulated in irradiated intestine tissues, but not in liver or lung tissues. Antibacterial and antifungal regents reduced the expression of ASCL4 and protected against tissue injury in irradiated intestine tissues. Further studies showed that troglitazone, a ACSL4 inhibitor, succeeded to suppresses intestine lipid peroxidation and tissue damage after IR.

Details

Title
ACSL4 is essential for radiation-induced intestinal injury by initiating ferroptosis
Author
Ji, Qian 1 ; Fu, Shengqiao 1 ; Zuo, Hao 2 ; Huang, Yumeng 3 ; Chu, Liangmei 1 ; Zhu, Yanyan 3 ; Hu, Jing 1 ; Wu, Yuting 4 ; Chen, Shuangwei 5 ; Wang, Yue 5 ; Ren, Yongfei 5 ; Pu, Xi 1 ; Liu, Na 6 ; Li, Rongkun 1   VIAFID ORCID Logo  ; Wang, Xu 1   VIAFID ORCID Logo  ; Dai, Chunhua 1   VIAFID ORCID Logo 

1  Jiangsu University, Department of Radiation Oncology, Institute of Oncology, Affiliated Hospital, Zhenjiang, China (GRID:grid.440785.a) (ISNI:0000 0001 0743 511X) 
2  Jiangsu University, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Zhenjiang, China (GRID:grid.440785.a) (ISNI:0000 0001 0743 511X) 
3  Jiangsu University, Department of Burn and Plastic Surgery, Affiliated Hospital, Zhenjiang, China (GRID:grid.440785.a) (ISNI:0000 0001 0743 511X) 
4  Jiangsu University, Department of Gastroenterology, Affiliated Hospital, Zhenjiang, China (GRID:grid.440785.a) (ISNI:0000 0001 0743 511X) 
5  Jiangsu University, Department of Emergency Surgery, Affiliated Hospital, Zhenjiang, China (GRID:grid.440785.a) (ISNI:0000 0001 0743 511X) 
6  The Affiliated People’s Hospital of Jiangsu University, Department of Neurology, Zhenjiang, China (GRID:grid.452247.2) 
Publication year
2022
Publication date
2022
Publisher
Springer Nature B.V.
e-ISSN
20587716
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41420-022-01127-w
ProQuest document ID
2692889209
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.