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Hydrogen Sulfide Suppresses Oxidized Low-density Lipoprotein (Ox-LDL)-stimulated Monocyte Chemoattractant Protein 1 generation from Macrophages via the Nuclear Factor kB ( NF- kB) Pathway*
Du, Junbao1; Huang, Yaqian1; Yan, Hui1; Zhang, Qiaoli1; Zhao, Manman1; Zhu, Mingzhu1; Liu, Jia1; Chen, Stella X.3; Bu, Dingfang2; Tang, Chaoshu4,5; Jin, Hongfang1
关键词Hydrogen Sulfide Inflammation Macrophages Nf-b Sulfhydryl
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
2014-04-04
DOI10.1074/jbc.M113.517995
289期:14页:9741-9753
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]FACTOR-KAPPA-B ; BLOOD MONONUCLEAR LEUKOCYTES ; HUMAN ENDOTHELIAL-CELLS ; SMOOTH-MUSCLE CELLS ; GENE-EXPRESSION ; MESANGIAL CELLS ; ALPHA KINASE ; ACTIVATION ; MCP-1 ; P65
英文摘要

Background: The mechanisms by which H2S regulates inflammation remain unclear. Results: H2S inhibits NF-B p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to MCP-1 promoter in ox-LDL-treated macrophages by targeting the free sulfhydryl group on cysteine 38 in p65. Conclusion: H2S inhibits macrophage inflammation by suppressing NF-B activation. Significance: These findings reveal mechanisms for regulation of NF-B pathway by H2S.

This study was designed to examine the role of hydrogen sulfide (H2S) in the generation of oxidized low-density lipoprotein (ox-LDL)-stimulated monocyte chemoattractant protein 1 (MCP-1) from macrophages and possible mechanisms. THP-1 cells and RAW macrophages were pretreated with sodium hydrosulfide (NaHS) and hexyl acrylate and then treated with ox-LDL. The results showed that ox-LDL treatment down-regulated the H2S/cystathionine--synthase pathway, with increased MCP-1 protein and mRNA expression in both THP-1 cells and RAW macrophages. Hexyl acrylate promoted ox-LDL-induced inflammation, whereas the H2S donor NaHS inhibited it. NaHS markedly suppressed NF-B p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter in ox-LDL-treated macrophages. Furthermore, NaHS decreased the ratio of free thiol groups in p65, whereas the thiol reductant DTT reversed the inhibiting effect of H2S on the p65 DNA binding activity. Most importantly, site-specific mutation of cysteine 38 to serine in p65 abolished the effect of H2S on the sulfhydration of NF-B and ox-LDL-induced NF-B activation. These results suggested that endogenous H2S inhibited ox-LDL-induced macrophage inflammation by suppressing NF-B p65 phosphorylation, nuclear translocation, DNA binding activity, and recruitment to the MCP-1 promoter. The sulfhydration of free thiol group on cysteine 38 in p65 served as a molecular mechanism by which H2S inhibited NF-B pathway activation in ox-LDL-induced macrophage inflammation.

语种英语
WOS记录号WOS:000333807000026
项目编号2011CB503904 ; 2012CB517806 ; 2013CB933801 ; 30901620 ; 31130030 ; 30821001 ; 7122184 ; 7121014
资助机构Major Basic Research Development Program of People&prime ; s Republic of China ; National Natural Science Foundation of China ; Beijing Natural Science Foundation
引用统计
被引频次:39[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/400002259/54148
专题北京大学第一临床医学院_儿科
作者单位1.Minist Educ, Key Lab Mol Cardiol, Beijing 100191, Peoples R China
2.Peking Univ, Hosp 1, Cent Lab, Beijing 100034, Peoples R China
3.Peking Univ, Dept Pediat, Hosp 1, Beijing 100034, Peoples R China
4.Univ Calif San Diego, Dept Biochem & Cellular Biol, La Jolla, CA 92092 USA
5.Peking Univ, Hlth Sci Ctr, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Du, Junbao,Huang, Yaqian,Yan, Hui,et al. Hydrogen Sulfide Suppresses Oxidized Low-density Lipoprotein (Ox-LDL)-stimulated Monocyte Chemoattractant Protein 1 generation from Macrophages via the Nuclear Factor kB ( NF- kB) Pathway*[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2014,289(14):9741-9753.
APA Du, Junbao.,Huang, Yaqian.,Yan, Hui.,Zhang, Qiaoli.,Zhao, Manman.,...&Jin, Hongfang.(2014).Hydrogen Sulfide Suppresses Oxidized Low-density Lipoprotein (Ox-LDL)-stimulated Monocyte Chemoattractant Protein 1 generation from Macrophages via the Nuclear Factor kB ( NF- kB) Pathway*.JOURNAL OF BIOLOGICAL CHEMISTRY,289(14),9741-9753.
MLA Du, Junbao,et al."Hydrogen Sulfide Suppresses Oxidized Low-density Lipoprotein (Ox-LDL)-stimulated Monocyte Chemoattractant Protein 1 generation from Macrophages via the Nuclear Factor kB ( NF- kB) Pathway*".JOURNAL OF BIOLOGICAL CHEMISTRY 289.14(2014):9741-9753.
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