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学科主题基础医学
Nonenzymatic glycation of high-density lipoprotein impairs its anti-inflammatory effects in innate immunity
Liu, Donghui2,3; Ji, Liang2,3; Zhang, Dongmei1; Tong, Xunliang6; Pan, Bing2,3; Liu, Pinli4; Zhang, Youyi2,3; Huang, Yining6; Su, Jinzi5; Willard, Belinda1; Zheng, Lemin2,3
关键词Hdl Type 2 Diabetes Mellitus Glycation Inflammation
刊名DIABETES-METABOLISM RESEARCH AND REVIEWS
2012-02-01
DOI10.1002/dmrr.1297
28期:2页:186-195
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]NECROSIS-FACTOR-ALPHA ; ENDOTHELIAL-CELLS ; MASS-SPECTROMETRY ; OXIDATIVE STRESS ; HDL ; EXPRESSION ; LIPOPOLYSACCHARIDE ; CHOLESTEROL ; GLYCOSYLATION ; ENDOTOXEMIA
英文摘要

Aims/hypothesis In type 2 diabetes mellitus (T2DM), the abnormal protein and lipid composition of diabetic high-density lipoprotein (HDL) could impair its anti-inflammatory functions. Whether nonenzymatic glycation directly impaired the anti-inflammatory effects of HDL in innate immunity remained unclear.

Methods Human acute monocytic leukemia cell line (THP-1) cells, mouse RAW 264.7 macrophages and primary human monocytes derived macrophages were pre-incubated with native HDL, diabetic HDL isolated from T2DM patients or HDL glycated with different doses of D-glucose in vitro and then challenged with lipopolysaccharide (LPS). The release of tumor necrosis factor (TNF)-alpha and IL-1 beta was assayed by enzyme-linked immunosorbent assay (ELISA). Phosphorylation of I kappa-B alpha in cytoplasm and nuclear translocation of NF-kappa B were detected by western blot. Glycation levels of native HDL, glycated HDL and diabetic HDL were determined using LC-MS/MS.

Results The potency of diabetic HDL to inhibit the release of TNF-alpha (p < 0.05) and IL-1 beta (p < 0.001) was dramatically attenuated compared with that of native HDL. Similarly, glycation of HDL in vitro impaired its ability to inhibit TNF-alpha and IL-1 beta release in a glucose dose-dependent manner. Moreover, apoHDL still effectively inhibited the release of TNF-alpha and IL-1 beta induced by LPS, but glycated apoHDL partly lost such abilities. Nonenzymatic glycation levels of glycated HDL and diabetic HDL increased 28 fold (p < 0.001) and 4 fold (p < 0.001), respectively compared with that of native HDL.

Conclusions In this study, we observed that diabetic HDL and HDL glycated in vitro both partly lose their protective effects to inhibit cytokines release induced by LPS in macrophages, and nonenzymatic glycation of the protein components of HDL plays key roles in these impairments. Copyright (C) 2011 John Wiley & Sons, Ltd.

语种英语
WOS记录号WOS:000300502100012
项目编号30900595 ; 30821001 ; 7102104 ; 2010CB912504 ; 2011CB503900 ; 2009 J01112 ; 20090001120039 ; 20100001120034
资助机构National Natural Science Foundation of China ; Natural Science Foundation of Beijing ; "973" National ST Major Project ; Natural Science Foundation of Fujian ; State Education Ministry of China
引用统计
被引频次:24[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56190
专题北京大学基础医学院_心血管所
北京大学基础医学院
北京大学第一临床医学院_神经内科
作者单位1.Cleveland Clin, Prote Lab, Cleveland, OH 44195 USA
2.Peking Univ, Inst Cardiovasc Sci, Minist Educ, Hlth Sci Ctr, Beijing 100191, Peoples R China
3.Peking Univ, Key Lab Mol Cardiovasc Sci, Minist Educ, Hlth Sci Ctr, Beijing 100191, Peoples R China
4.Hebei Med Univ, Hosp 2, Dept Endocrinol, Shijiazhuang, Peoples R China
5.Fujian Med Univ, Dept Cardiol, Affiliated Hosp 1, Fuzhou, Fujian, Peoples R China
6.Peking Univ, Hosp 1, Dept Neurol, Beijing 100191, Peoples R China
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GB/T 7714
Liu, Donghui,Ji, Liang,Zhang, Dongmei,et al. Nonenzymatic glycation of high-density lipoprotein impairs its anti-inflammatory effects in innate immunity[J]. DIABETES-METABOLISM RESEARCH AND REVIEWS,2012,28(2):186-195.
APA Liu, Donghui.,Ji, Liang.,Zhang, Dongmei.,Tong, Xunliang.,Pan, Bing.,...&Zheng, Lemin.(2012).Nonenzymatic glycation of high-density lipoprotein impairs its anti-inflammatory effects in innate immunity.DIABETES-METABOLISM RESEARCH AND REVIEWS,28(2),186-195.
MLA Liu, Donghui,et al."Nonenzymatic glycation of high-density lipoprotein impairs its anti-inflammatory effects in innate immunity".DIABETES-METABOLISM RESEARCH AND REVIEWS 28.2(2012):186-195.
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