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论文题目: 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
英文论文题目: 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
第一作者: Lu, JH; Guo, SY; Xue, XL; Chen, Q; Ge, J; Zhuo, YJ; Zhong, HQ; Chen, BX; Zhao, MM; Han, W; Suzuki, T; Zhu, MJ; Xia, L; Schneider, C; Blackwell, TS; Porter, NA; Zheng, LM; Tsimikas, S; Yin, HY
英文第一作者: Lu, JH; Guo, SY; Xue, XL; Chen, Q; Ge, J; Zhuo, YJ; Zhong, HQ; Chen, BX; Zhao, MM; Han, W; Suzuki, T; Zhu, MJ; Xia, L; Schneider, C; Blackwell, TS; Porter, NA; Zheng, LM; Tsimikas, S; Yin, HY
联系作者: Yin, HY (reprint author), Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Rm 1826,New Life Sci Bldg,320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Yin, HY (reprint author), Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Rm 1826,New Life Sci Bldg,320 Yueyang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2017
卷: 292
期: 13
页码: 5378-5391
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.
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.
刊物名称: JOURNAL OF BIOLOGICAL CHEMISTRY
英文刊物名称: JOURNAL OF BIOLOGICAL CHEMISTRY
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学科: Biochemistry & Molecular Biology
英文学科: Biochemistry & Molecular Biology
影响因子: 4.125
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论文类别: Article
英文论文类别: Article
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