Intermittent Hypoxia and Its Impact on Nrf2/HIF-1α Expression and ABC Transporters: An in Vitro Human Blood-Brain Barrier Model Study.

粘合连接 并行传输 血脑屏障 紧密连接 缺氧(环境) 跨细胞 体外 间歇性缺氧 运输机 化学 细胞生物学 药理学 埃文斯蓝 生物 免疫学 阻塞性睡眠呼吸暂停 细胞 医学 内科学 钙粘蛋白 磁导率 内分泌学 生物化学 中枢神经系统 氧气 有机化学 基因
作者
Cindy Zolotoff,Anne-Cloé Voirin,C. Puech,Frédéric Roche,Nathalie Perek
出处
期刊:Cellular Physiology and Biochemistry [Cell Physiol Biochem Press GmbH and Co KG]
卷期号:54 (6): 1231-1248 被引量:29
标识
DOI:10.33594/000000311
摘要

BACKGROUND/AIMS: Obstructive sleep apnea (OSA) is characterized by repeated episodes of complete or partial obstruction of the upper airways, leading to chronic intermittent hypoxia (IH). OSA patients are considered at high cerebrovascular risk and may also present cognitive impairment. One hypothesis explored is that disturbances may be linked to blood-brain barrier (BBB) dysfunction. The BBB is a protective barrier separating the brain from blood flow. The BBB limits the paracellular pathway through tight and adherens junctions, and the transcellular passage by efflux pumps (ABC transporters). The aims of this study were to evaluate the impact of IH and sustained hypoxia (SH) on a validated in vitro BBB model and to investigate the factors expressed under both conditions. METHODS: Exposure of endothelial cells (HBEC-5i) in our in vitro model of BBB to hypoxia was performed using IH cycles: 1% O2-35 min/18% O2-25 min for 6 cycles or 6 h of SH at 1% O2. After exposure, we studied the cytotoxicity and the level of ROS in our cells. We measured the apparent BBB permeability using sodium fluorescein, FITC-dextran and TEER measurement. Whole cell ELISA were performed to evaluate the expression of tight junctions, ABC transporters, HIF-1α and Nrf2. The functionality of ABC transporters was evaluated with accumulation studies. Immunofluorescence assays were also conducted to illustrate the whole cell ELISAs. RESULTS: Our study showed that 6 h of IH or SH induced a BBB disruption marked by a significant decrease in junction protein expressions (claudin-5, VE-cadherin, ZO-1) and an increase in permeability. We also observed an upregulation in P-gp protein expression and functionality and a downregulation in BCRP. Hypoxia induced production of ROS, Nrf2 and HIF-1α. They were expressed in both sustained and intermittent conditions, but the expression and the activity of P-gp and BCRP were different. CONCLUSION: Understanding these mechanisms seems essential in order to propose new therapeutic strategies for patients with OSA
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
叫我小可爱完成签到,获得积分10
1秒前
打打应助假发君采纳,获得10
2秒前
淡定小翠发布了新的文献求助10
3秒前
66完成签到,获得积分10
3秒前
youbin完成签到 ,获得积分10
6秒前
猪猪hero发布了新的文献求助10
7秒前
优秀的一整天完成签到 ,获得积分10
7秒前
土豪的钻石完成签到,获得积分10
10秒前
13秒前
平淡豁完成签到,获得积分10
14秒前
17秒前
此话当真发布了新的文献求助10
17秒前
HYX完成签到,获得积分10
17秒前
lebron发布了新的文献求助10
18秒前
大胆的弼完成签到,获得积分10
18秒前
19秒前
淞淞于我完成签到 ,获得积分10
19秒前
细腻冬易完成签到,获得积分10
20秒前
科研通AI2S应助monkey采纳,获得10
23秒前
HYX发布了新的文献求助10
25秒前
春国应助科研通管家采纳,获得10
25秒前
科研通AI2S应助科研通管家采纳,获得10
25秒前
完美世界应助科研通管家采纳,获得10
25秒前
田様应助科研通管家采纳,获得10
25秒前
乌龟娟应助科研通管家采纳,获得10
25秒前
春国应助科研通管家采纳,获得10
26秒前
脑洞疼应助科研通管家采纳,获得10
26秒前
jst应助科研通管家采纳,获得60
26秒前
26秒前
科研通AI2S应助科研通管家采纳,获得10
26秒前
小二郎应助科研通管家采纳,获得10
26秒前
27秒前
科研通AI2S应助sidneyyang采纳,获得10
27秒前
三太子完成签到,获得积分10
27秒前
31秒前
坦率的枕头完成签到,获得积分10
31秒前
文龙发布了新的文献求助10
36秒前
大个应助木子李采纳,获得10
37秒前
我是老大应助时尚的醉蓝采纳,获得30
43秒前
44秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2000
Very-high-order BVD Schemes Using β-variable THINC Method 1200
RNAの科学 ―時代を拓く生体分子― 金井 昭夫(編) 1000
BIOLOGY OF NON-CHORDATES 1000
进口的时尚——14世纪东方丝绸与意大利艺术 Imported Fashion:Oriental Silks and Italian Arts in the 14th Century 800
Autoregulatory progressive resistance exercise: linear versus a velocity-based flexible model 550
The Collected Works of Jeremy Bentham: Rights, Representation, and Reform: Nonsense upon Stilts and Other Writings on the French Revolution 320
热门求助领域 (近24小时)
化学 医学 生物 材料科学 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 细胞生物学 免疫学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3354316
求助须知:如何正确求助?哪些是违规求助? 2978688
关于积分的说明 8686928
捐赠科研通 2660273
什么是DOI,文献DOI怎么找? 1456569
科研通“疑难数据库(出版商)”最低求助积分说明 674407
邀请新用户注册赠送积分活动 665247