Diabetes-Associated Sustained Activation of the Transcription Factor Nuclear Factor-κB

愤怒(情绪) 转录因子 糖基化 P50页 AP-1转录因子 内分泌学 内科学 生物 NF-κB NFKB1型 细胞生物学 受体 转基因 分子生物学 体外 信号转导 医学 糖尿病 生物化学 基因 神经科学
作者
Angelika Bierhaus,Stephan Schiekofer,Markus Schwaninger,Martin Andrassy,Per M. Humpert,Jiang Chen,Mei Hong,Thomas Luther,Thomas Henle,Ingrid Klöting,Michael Morcos,M. Hofmann,Hans Tritschler,Bernd Weigle,Michael Kasper,Mark A. Smith,George Perry,Ann-Marie Schmidt,David M. Stern,Hans‐Ulrich Häring
出处
期刊:Diabetes [American Diabetes Association]
卷期号:50 (12): 2792-2808 被引量:814
标识
DOI:10.2337/diabetes.50.12.2792
摘要

Activation of the transcription factor nuclear factor-κB (NF-κB) has been suggested to participate in chronic disorders, such as diabetes and its complications. In contrast to the short and transient activation of NF-κB in vitro, we observed a long-lasting sustained activation of NF-κB in the absence of decreased IκBα in mononuclear cells from patients with type 1 diabetes. This was associated with increased transcription of NF-κBp65. A comparable increase in NF-κBp65 antigen and mRNA was also observed in vascular endothelial cells of diabetic rats. As a mechanism, we propose that binding of ligands such as advanced glycosylation end products (AGEs), members of the S100 family, or amyloid-β peptide (Aβ) to the transmembrane receptor for AGE (RAGE) results in protein synthesis–dependent sustained activation of NF-κB both in vitro and in vivo. Infusion of AGE-albumin into mice bearing a β-globin reporter transgene under control of NF-κB also resulted in prolonged expression of the reporter transgene. In vitro studies showed that RAGE-expressing cells induced sustained translocation of NF-κB (p50/p65) from the cytoplasm into the nucleus for >1 week. Sustained NF-κB activation by ligands of RAGE was mediated by initial degradation of IκB proteins followed by new synthesis of NF-κBp65 mRNA and protein in the presence of newly synthesized IκBα and IκBβ. These data demonstrate that ligands of RAGE can induce sustained activation of NF-κB as a result of increased levels of de novo synthesized NF-κBp65 overriding endogenous negative feedback mechanisms and thus might contribute to the persistent NF-κB activation observed in hyperglycemia and possibly other chronic diseases.
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
PDF的下载单位、IP信息已删除 (2025-6-4)

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
1秒前
健康萝卜发布了新的文献求助10
2秒前
NexusExplorer应助姗姗采纳,获得30
3秒前
科目三应助翟翟采纳,获得10
3秒前
唐僧肉臊子面完成签到,获得积分10
4秒前
呐呐发布了新的文献求助10
5秒前
6秒前
9秒前
科研通AI6应助小李呀采纳,获得10
9秒前
老阎应助Yule采纳,获得30
10秒前
桑祥发布了新的文献求助10
10秒前
11秒前
謃河鷺起完成签到,获得积分10
12秒前
Lucifer完成签到,获得积分10
12秒前
科研通AI5应助霸气凡白采纳,获得10
13秒前
科研通AI6应助蝶步韶华采纳,获得10
13秒前
姗姗完成签到,获得积分20
14秒前
15秒前
Fxxkme发布了新的文献求助10
15秒前
16秒前
17秒前
着急的青枫应助Lucifer采纳,获得10
17秒前
顾矜应助ldc采纳,获得10
20秒前
21秒前
xzy998应助翟翟采纳,获得10
22秒前
22秒前
朱光辉发布了新的文献求助10
24秒前
完美世界应助yjwang采纳,获得10
24秒前
GAWAIN完成签到 ,获得积分10
26秒前
27秒前
佰斯特威发布了新的文献求助10
27秒前
Samuel完成签到 ,获得积分10
27秒前
赵纤完成签到,获得积分10
28秒前
30秒前
蝶步韶华发布了新的文献求助10
30秒前
田様应助朱光辉采纳,获得10
32秒前
乐乐应助倪塔宝贝采纳,获得10
32秒前
顺心的若雁完成签到,获得积分10
33秒前
刘111发布了新的文献求助10
34秒前
PGONE应助沐雨采纳,获得10
34秒前
高分求助中
(应助此贴封号)【重要!!请各用户(尤其是新用户)详细阅读】【科研通的精品贴汇总】 10000
Rapid Review of Electrodiagnostic and Neuromuscular Medicine: A Must-Have Reference for Neurologists and Physiatrists 1000
求中国石油大学(北京)图书馆的硕士论文,作者董晨,十年前搞太赫兹的 500
Narrative Method and Narrative form in Masaccio's Tribute Money 500
基于3um sOl硅光平台的集成发射芯片关键器件研究 500
Educational Research: Planning, Conducting, and Evaluating Quantitative and Qualitative Research 460
Development in Infancy 400
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 内科学 生物化学 物理 计算机科学 纳米技术 遗传学 基因 复合材料 化学工程 物理化学 病理 催化作用 免疫学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 4784838
求助须知:如何正确求助?哪些是违规求助? 4111889
关于积分的说明 12720923
捐赠科研通 3836668
什么是DOI,文献DOI怎么找? 2115392
邀请新用户注册赠送积分活动 1138391
关于科研通互助平台的介绍 1024489