Identification of a novel series of anti-inflammatory and anti-oxidative phospholipid oxidation products containing the cyclopentenone moiety in vitro and in vivo: Implication in atherosclerosis
文献类型:期刊论文
作者 | Lu, Jianhong1,2,3; Guo, Shuyuan1,2,3; Xue, Xinli1,2,3; Chen, Qun1,2,3; Zhuo, Yujuan1,2,3,4; Zhong, Huiqin1,2,3; Zhu, Mingjiang1,3; Xia, Lin1,3; Yin, Huiyong1,2,3,4; Guo, Shuyuan4 |
刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY |
出版日期 | 2017 |
卷号 | 292期号:13页码:5378-5391 |
ISSN号 | 0021-9258 |
关键词 | cardiovascular disease endocardium ligation mice myocardium |
DOI | 10.1074/jbc.M116.751909 |
文献子类 | Article |
英文摘要 | Oxidative stress and inflammation are two major contributing factors to atherosclerosis, a leading cause of cardiovascular disease. Oxidation of phospholipids on the surface of low density lipoprotein (LDL) particles generated under oxidative stress has been associated with the progression of atherosclerosis, but the underlying molecular mechanisms remain poorly defined. We identified a novel series of oxidation products containing the cyclopentenone moiety, termed deoxy-A(2)/J(2)-isoprostanesphosphocholine, from 1-palmitoyl-2-arachidonoyl-sn-glycero3- phosphocholine in vivo using mass spectrometry and by comparison to a chemically synthesized standard. Transcriptomic analysis (RNA-seq) demonstrated that these compounds affected > 200 genes in bone marrow-derived macrophages, and genes associated with inflammatory and anti-oxidative responses are among the top 5 differentially expressed. To further investigate the biological relevance of these novel oxidized phospholipids in atherosclerosis, we chemically synthesized a representative compound 1-palmitoyl-2-15-deoxy-delta-12,14prostaglandin J(2)-sn-glycero-3-phosphocholine (15d-PGJ(2)-PC) and found that it induced anti-inflammatory and anti-oxidant responses in macrophages through modulation of NF-kappa B, peroxisome proliferator-activated receptor gamma (PPAR gamma), and Nrf2 pathways; this compound also showed potent anti-inflammatory properties in a mice model of LPS-induced systematic inflammatory response syndrome. Additionally, 15d-PGJ(2)-PC inhibited macrophage foam cell formation, suggesting a beneficial role against atherosclerosis. These properties were consistent with decreased levels of these compounds in the plasma of patients with coronary heart disease compared with control subjects. Our findings uncovered a novel molecular mechanism for the negative regulation of inflammation and positive enhancement of anti-oxidative responses in macrophages by these oxidized phospholipids in LDL in the context of atherosclerosis. |
学科主题 | Biochemistry & Molecular Biology |
WOS关键词 | LOW-DENSITY-LIPOPROTEIN ; FOAM CELL-FORMATION ; OXIDIZED PHOSPHOLIPIDS ; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2) ; STRUCTURAL IDENTIFICATION ; MASS-SPECTROMETRY ; MACROPHAGES ; PATHWAY ; INFLAMMATION ; GENERATION |
语种 | 英语 |
出版者 | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC |
WOS记录号 | WOS:000397875500019 |
版本 | 出版稿 |
源URL | [http://202.127.25.144/handle/331004/1024] |
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.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Key Lab food safety Res, Shanghai 200031, Peoples R China; 2.Chinese Acad Sci, Univ Chinese Acad Sci, Beijing 100049, Peoples R China; 3.Minist Hlth, Key Lab food safety risk Assessment, Beijing 100000, Peoples R China; 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Key Lab Syst Biol, Shanghai 200031, Peoples R China; 6.Capital Med Univ, Beijing Tiantan Hosp, Dept Cardiol, Beijing 100050, Peoples R China; 7.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China; 8.Peking Univ, Hlth Sci Ctr, Inst Syst Biomed, Sch Basic Med Sci,Key Lab Mol Cardiovasc Sci,Mini, Beijing 100191, Peoples R China; 9.Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA; 10.Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Dept Pharmacol, Nashville, TN 37232 USA; |
推荐引用方式 GB/T 7714 | Lu, Jianhong,Guo, Shuyuan,Xue, Xinli,et al. Identification of a novel series of anti-inflammatory and anti-oxidative phospholipid oxidation products containing the cyclopentenone moiety in vitro and in vivo: Implication in atherosclerosis[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2017,292(13):5378-5391. |
APA | Lu, Jianhong.,Guo, Shuyuan.,Xue, Xinli.,Chen, Qun.,Zhuo, Yujuan.,...&,.(2017).Identification of a novel series of anti-inflammatory and anti-oxidative phospholipid oxidation products containing the cyclopentenone moiety in vitro and in vivo: Implication in atherosclerosis.JOURNAL OF BIOLOGICAL CHEMISTRY,292(13),5378-5391. |
MLA | Lu, Jianhong,et al."Identification of a novel series of anti-inflammatory and anti-oxidative phospholipid oxidation products containing the cyclopentenone moiety in vitro and in vivo: Implication in atherosclerosis".JOURNAL OF BIOLOGICAL CHEMISTRY 292.13(2017):5378-5391. |
入库方式: OAI收割
来源:上海营养与健康研究所
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