CPT1 Mediated Ionizing Radiation-Induced Intestinal Injury Proliferation via Shifting FAO Metabolism Pathway and Activating the ERK1/2 and JNK Pathway

生物 小肠 内科学 内分泌学 医学
作者
Haixiang Liu,Zhao Hua,Cong Xi,Shuang Li,Li-Ping Ma,Xue Lü,Juan Yan,Xue-Lei Tian,Ling Gao,Mei Tian,Qing-Jie Liu
出处
期刊:Radiation Research [Radiation Research Society]
卷期号:198 (5) 被引量:2
标识
DOI:10.1667/rade-21-00174.1
摘要

The intestinal compensatory proliferative potential is a key influencing factor for susceptibility to radiation-induced intestinal injury. Studies indicated that the carnitine palmitoyltransferase 1 (CPT1) mediated fatty acid β-oxidation (FAO) plays a crucial role in promoting the survival and proliferation of tumor cells. Here, we aimed to explore the effect of 60Co gamma rays on CPT1 mediated FAO in the radiation-induced intestinal injury models, and investigate the role of CPT1 mediated FAO in the survival and proliferation of intestinal cells after irradiation. We detected the changed of FAO in the plasma and small intestine of Sprague Dawley (SD) rats at 24 h after 60Co gamma irradiation (0, 5 and 10 Gy), using target metabolomics, qRT-PCR, immunohistochemistry (IHC), western blot (WB) and related enzymatic activity kits. We then analyzed the FAO changes in radiation-induced intestinal injury models regardless of ex vivo (mice enteroids), or in vitro (normal human intestinal epithelial cell lines, HIEC-6). HIEC-6 cells were transduced with lentivirus vector GV392 and treated with puromycin for obtaining CPT1 stable knockout cell lines, named CPT1 KO. CPT1 enzymatic activities of HIEC-6 cells and mice enteroids were also inhibited by pharmaceutical inhibitor ST1326 and Etomoxir (ETO), to study the function of CPT1 in the survival and proliferation of HIEC-6 cells after 60Co gamma irradiation. We found that CPT1 mediated FAO was altered in the small intestine of the SD rats after irradiation, especially, the expression level and enzymatic activity of CPT1 were significantly increased. Similarly, the expression levels of CPT1 were also remarkably enhanced in mice enteroids and HIEC-6 cells after irradiation. CPT1 inhibition decreased the proliferation of the HIEC-6 cells and mice enteroids after irradiation partially by reducing the extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) pathways activation, CPT1 inhibition also reduced the proliferation of mice enteroids after irradiation partially by down-regulating the Wnt/β-catenin signaling activity. In conclusion, our study indicated that CPT1 plays a crucial role in promoting intestinal epithelial cell proliferation after irradiation.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
封皮人发布了新的文献求助10
刚刚
刚刚
1秒前
脑洞疼应助11111111111111采纳,获得10
2秒前
2秒前
七七发布了新的文献求助10
2秒前
一苇以航发布了新的文献求助20
3秒前
3秒前
Tu发布了新的文献求助30
3秒前
极品小亮完成签到,获得积分10
4秒前
天天天蓝完成签到,获得积分10
4秒前
妮妮完成签到,获得积分10
5秒前
优秀瑞发布了新的文献求助10
5秒前
飞快的珩发布了新的文献求助10
5秒前
英姑应助liugm采纳,获得10
7秒前
7秒前
jagger完成签到,获得积分10
7秒前
8秒前
小马甲应助古炮采纳,获得50
10秒前
feizao完成签到,获得积分10
10秒前
WUYONGSHUAI发布了新的文献求助10
11秒前
Vicky完成签到 ,获得积分10
11秒前
封皮人完成签到,获得积分10
12秒前
谦让的梦山完成签到,获得积分10
14秒前
YUUNEEQUE完成签到,获得积分10
14秒前
s1kl完成签到,获得积分10
15秒前
今天想吃披萨完成签到,获得积分10
15秒前
15秒前
满意的迎南完成签到 ,获得积分10
17秒前
林非鹿完成签到 ,获得积分10
17秒前
钱从四面八方来完成签到 ,获得积分10
18秒前
科研通AI2S应助苗自中采纳,获得10
18秒前
欢乐的水牛完成签到,获得积分10
19秒前
AAA完成签到,获得积分10
21秒前
蹇蹇完成签到 ,获得积分10
24秒前
25秒前
阳光总在风雨后完成签到,获得积分10
26秒前
26秒前
悄悄.完成签到,获得积分10
27秒前
七七完成签到,获得积分10
29秒前
高分求助中
Technologies supporting mass customization of apparel: A pilot project 600
Introduction to Strong Mixing Conditions Volumes 1-3 500
Tip60 complex regulates eggshell formation and oviposition in the white-backed planthopper, providing effective targets for pest control 400
A Field Guide to the Amphibians and Reptiles of Madagascar - Frank Glaw and Miguel Vences - 3rd Edition 400
China Gadabouts: New Frontiers of Humanitarian Nursing, 1941–51 400
The Healthy Socialist Life in Maoist China, 1949–1980 400
Walking a Tightrope: Memories of Wu Jieping, Personal Physician to China's Leaders 400
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3798970
求助须知:如何正确求助?哪些是违规求助? 3344671
关于积分的说明 10321176
捐赠科研通 3061162
什么是DOI,文献DOI怎么找? 1680049
邀请新用户注册赠送积分活动 806877
科研通“疑难数据库(出版商)”最低求助积分说明 763429