Absence of ABCG2-mediated mucosal detoxification in patients with active inflammatory bowel disease is due to impeded protein folding

未折叠蛋白反应 炎症 炎症性肠病 Abcg2型 免疫学 结肠炎 氧化应激 化学 生物 医学 运输机 内科学 ATP结合盒运输机 疾病 生物化学 内质网 基因
作者
J. Jasper Deuring,Colin de Haar,Chantal L Koelewijn,Ernst J. Kuipers,Maikel P. Peppelenbosch,Jean–Frédéric Colombel
出处
期刊:Biochemical Journal [Portland Press]
卷期号:441 (1): 87-93 被引量:38
标识
DOI:10.1042/bj20111281
摘要

Xenotoxic damage in inflammatory diseases, including IBD (inflammatory bowel disease), is compounded by reduced activity of the xenobiotic transporter ABCG2 (ATP-binding-cassette G2) during the inflammatory state. An association between the activation of the unfolded protein response pathway and inflammation prompted us to investigate the possibility that reduced ABCG2 activity is causally linked to this response. To this end, we correlated expression of ABCG2 and the unfolded protein response marker GRP78 (glucose-regulated protein of 78 kDa) in colon biopsies from healthy individuals (n=9) and patients with inactive (n=67) or active (n=55) IBD, ischaemic colitis (n=10) or infectious colitis (n=14). In addition, tissue specimens throughout the small bowel from healthy individuals (n=27) and from patients with inactive (n=9) or active (n=25) Crohn's disease were co-stained for ABCG2 and GRP78. In all biopsies from patients with active inflammation, irrespective of the underlying disease, an absolute negative correlation was observed between epithelial ABCG2 expression and GRP78 expression, suggesting that inflammation-dependent activation of the unfolded protein response is responsible for suppression of ABCG2 function. The link between the unfolded protein response and functional ABCG2 expression was further corroborated by live imaging of ABCG2-expressing cells, which showed that various inflammatory mediators, including nitric oxide, activate the unfolded protein response and concomitantly reduce plasma membrane localization as well as transport function of ABCG2. Thus a novel mechanism for explaining xenobiotic stress during inflammation emerges in which intestinal inflammation activates the unfolded protein response, in turn abrogating defences against xenobiotic challenge by impairing ABCG2 expression and function.
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
更新
大幅提高文件上传限制,最高150M (2024-4-1)

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
刚刚
小巴发布了新的文献求助10
3秒前
瓦罐完成签到 ,获得积分10
5秒前
zjj完成签到,获得积分10
8秒前
applelpypies完成签到 ,获得积分0
11秒前
Xu_W卜完成签到,获得积分10
11秒前
姜姜完成签到 ,获得积分10
13秒前
小巴完成签到,获得积分10
14秒前
16秒前
hh完成签到,获得积分10
18秒前
盈盈完成签到,获得积分10
21秒前
123完成签到,获得积分10
23秒前
24秒前
盈盈发布了新的文献求助10
25秒前
YUNUN完成签到,获得积分10
25秒前
今后应助科研通管家采纳,获得10
26秒前
ZeKaWa应助科研通管家采纳,获得10
26秒前
吴彦祖应助科研通管家采纳,获得20
26秒前
隐形曼青应助科研通管家采纳,获得10
26秒前
完美世界应助科研通管家采纳,获得30
26秒前
29秒前
linxm7完成签到,获得积分10
30秒前
33秒前
小蘑菇应助璀璨c采纳,获得10
33秒前
领导范儿应助dicy1232003采纳,获得10
38秒前
42秒前
42秒前
科研通AI2S应助Micale采纳,获得10
43秒前
岩墩墩完成签到 ,获得积分10
43秒前
万能图书馆应助鸢尾采纳,获得10
45秒前
45秒前
sulh发布了新的文献求助10
47秒前
小硕完成签到,获得积分10
48秒前
旺旺发布了新的文献求助10
48秒前
阳佟念真完成签到,获得积分10
50秒前
dicy1232003发布了新的文献求助10
51秒前
NEVERLAND1958完成签到 ,获得积分10
51秒前
53秒前
泽辰发布了新的文献求助10
54秒前
卓矢完成签到 ,获得积分10
54秒前
高分求助中
One Man Talking: Selected Essays of Shao Xunmei, 1929–1939 1000
A Chronicle of Small Beer: The Memoirs of Nan Green 1000
From Rural China to the Ivy League: Reminiscences of Transformations in Modern Chinese History 900
Eric Dunning and the Sociology of Sport 850
QMS18Ed2 | process management. 2nd ed 800
Operative Techniques in Pediatric Orthopaedic Surgery 510
The Making of Détente: Eastern Europe and Western Europe in the Cold War, 1965-75 500
热门求助领域 (近24小时)
化学 医学 材料科学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 免疫学 细胞生物学 电极
热门帖子
关注 科研通微信公众号,转发送积分 2914287
求助须知:如何正确求助?哪些是违规求助? 2551853
关于积分的说明 6904790
捐赠科研通 2214342
什么是DOI,文献DOI怎么找? 1176823
版权声明 588293
科研通“疑难数据库(出版商)”最低求助积分说明 576248