title: Regulatory role of thioredoxin in homocysteine-induced monocyte chemoattractant protein-1 secretion in monocytes/macrophages.
abstract: We have previously shown that homocysteine (Hcy) can induce monocyte chemoattractant protein-1 (MCP-1) secretion via reactive oxygen species (ROS) in human monocytes. Here, we show that Hcy upregulates expression of an important antioxidative protein, thioredoxin (Trx), via NADPH oxidase in human monocytes in vitro. The increase of Trx expression and activity inhibited Hcy-induced ROS production and MCP-1 secretion. Of note, 2-week hyperhomocysteinemia (HHcy) ApoE(-/-) mice showed accelerated lesion formation and parallel lower Trx expression in macrophages than ApoE(-/-) mice, suggesting that HHcy-induced sustained oxidative stress in vivo might account for impaired Trx and hence increased ROS production and MCP-1 secretion from macrophages, and subsequently accelerated atherogenesis.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Science, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100083, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dai
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
authors.forename: Xun
authors.initials: X
authors.lastname: Shen
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D006710:Homocysteine / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D017382:Reactive Oxygen Species; D013879:Thioredoxins / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D001057:Apolipoproteins E; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D017382:Reactive Oxygen Species; D006710:Homocysteine; D013879:Thioredoxins; D019255:NADPH Oxidases