Lysine glycation of apolipoprotein A-I impairs its anti-inflammatory function in type 2 diabetes mellitus
文献类型:期刊论文
作者 | Liu, Donghui2,6; Ji, Liang2; Zhao, Mingming2; Pan, Bing2; Li, Jingxuan2; Gao, Jianing2; Zheng, Lemin2; Li, Ling3; Zhang, Dongmei3; Willard, Belinda3 |
刊名 | JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
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出版日期 | 2018 |
卷号 | 122期号:-页码:47-57 |
关键词 | HDL Apolipoprotein Glycation Proteomics Inflammation |
ISSN号 | 0022-2828 |
DOI | 10.1016/j.yjmcc.2018.08.001 |
文献子类 | Article |
英文摘要 | Apolipoprotein A-I (apoA-I), the major protein compontent of high-density lipoprotein (HDL), exerts many anti-atherogenic functions. This study aimed to reveal whether nonenzymatic glycation of specific sites of apoA-I impaired its anti-inflammatory effects in type 2 diabetes mellitus (T2DM). LC-MS/MS was used to analyze the specific sites and the extent of apoA-I glycation either modified by glucose in vitro or isolated from T2DM patients. Cytokine release in THP-1 monocyte-derived macrophages was tested by ELISA. Activation of NF-kappa B pathway was detected by western blot. The binding affinity of apoA-I to THP-1 cells was measured using I-125 labeled apoA-I. We identified seven specific lysine (Lys, K) residues of apoA-I (K12, K23, K40, K96, K106, K107 and K238) that were susceptible to be glycated either in vitro or in vivo. Glycation of apoA-I impaired its abilities to inhibit the release of TNF-alpha and IL-1 beta against lipopolysaccharide (LPS) in THP-1 cells. Besides, the glycation levels of these seven K sites in apoA-I were inversely correlated with its anti-inflammatory abilities. Furthermore, glycated apoA-I had a lower affinity to THP-1 cells than native apoA-I had. We generated mutant apoA-I (K107E, M-apoA-I) with a substitution of glutamic acid (Glu, E) for lysine at the 107th site, and found that compared to wild type apoA-I (WT-apoA-I), M-apoA-I decreased its anti-inflammatory effects in THP-1 cells. We also modeled the location of these seven K residues on apoA-I which allowed us to infer the conformational alteration of glycated apoA-I and HDL. In summary, glycation of these seven K residues altered the conformation of apoA-I and consequently impaired the protective effects of apoA-I, which may partly account for the increased risk of cardiovascular disease (CVD) in diabetic subjects. |
学科主题 | Cardiovascular System & Cardiology ; Cell Biology |
WOS关键词 | HIGH-DENSITY-LIPOPROTEIN ; LECITHIN-CHOLESTEROL ACYLTRANSFERASE ; CELL-SURFACE BINDING ; APOA-I ; NONENZYMATIC GLYCATION ; MASS-SPECTROMETRY ; CRYSTAL-STRUCTURE ; ALPHA-HELICES ; END-PRODUCTS ; HDL |
语种 | 英语 |
WOS记录号 | WOS:000445321700005 |
出版者 | ELSEVIER SCI LTD |
版本 | 出版稿 |
源URL | [http://202.127.25.144/handle/331004/761] ![]() |
专题 | 中国科学院上海生命科学研究院营养科学研究所 |
作者单位 | 1.Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA; 2.Peking Univ, Hlth Sci Ctr,Minist Hlth,Beijing Key Lab Cardiova, Inst Cardiovasc Sci,Minist Educ,Key Lab Cardiovas, Inst Syst Biomed,Sch Basic Med Sci,Key Lab Mol Ca, Beijing 100191, Peoples R China; 3.Cleveland Clin, Prote Lab, Cleveland, OH 44195 USA; 4.Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing, Peoples R China; 5.Fujian Med Univ, Affiliated Hosp 1, Dept Cardiol, Fuzhou 350005, Fujian, Peoples R China; 6.Xiamen Univ, Dept Cardiol, Affiliated Cardiovasc Hosp, Med Coll, Xiamen 361004, Fujian, Peoples R China; 7.Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci,Grad Sch, 294 Taiyuan Rd, Shanghai 200031, Peoples R China; 8.Fujian Prov Hosp, Dept Cardiovasc Med, Fuzhou, Fujian, Peoples R China, |
推荐引用方式 GB/T 7714 | Liu, Donghui,Ji, Liang,Zhao, Mingming,et al. Lysine glycation of apolipoprotein A-I impairs its anti-inflammatory function in type 2 diabetes mellitus[J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,2018,122(-):47-57. |
APA | Liu, Donghui.,Ji, Liang.,Zhao, Mingming.,Pan, Bing.,Li, Jingxuan.,...&,.(2018).Lysine glycation of apolipoprotein A-I impairs its anti-inflammatory function in type 2 diabetes mellitus.JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,122(-),47-57. |
MLA | Liu, Donghui,et al."Lysine glycation of apolipoprotein A-I impairs its anti-inflammatory function in type 2 diabetes mellitus".JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 122.-(2018):47-57. |
入库方式: OAI收割
来源:上海营养与健康研究所
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