|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|
|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|
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.
|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|
|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
|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.|
|Liu_et_al-2012-Diabe（351KB）||期刊论文||作者接受稿||开放获取||CC BY-NC-SA||浏览 请求全文|