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AOPPs inhibits cholesterol efflux by down-regulating ABCA1 expression in a JAK/STAT signaling pathway-dependent manner
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نویسنده
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mo z.-c. ,xiao j. ,liu x.-h. ,hu y.-w. ,li x.-x. ,yi g.-h. ,wang z. ,tang y.-l. ,liao d.-f. ,tang c.-k.
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منبع
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journal of atherosclerosis and thrombosis - 2011 - دوره : 18 - شماره : 9 - صفحه:796 -807
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چکیده
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Aims: advanced oxidation protein products (aopps) are new independent risk factor for coronary artery disease. this study was to determine the effects and potential mechanisms of aopps on cholesterol efflux from human macrophage foam cells. methods: human thp-1 monocytes were preincubated with phorbol-12-myristate- 13-acetate (pma) and oxidized low density lipoprotein (ox-ldl) to form foam cells. the protein and mrna expression were examined by western immunoblotting assays and real-time quantitative pcr,respectively. cellular cholesterol content was measured by hplc. the cholesterol efflux was assessed by liquid scintillation counting. results: aopps significantly decreased the expression of atp-binding membrane cassette transporter a-1 (abca1) and liver x receptor α (lxrα) and reduced cholesterol efflux from thp-1 macrophage- derived foam cells. aopps substantially activated nadph oxidase and activated janus kinase/ signal transducers and activators of transcription (jak/stat) signal pathway in thp-1-derived foam-like cells. inhibiting nadph oxidase by diphenyliodonium (dpi) effectively abolished the aopps-induced decrease in cholesterol efflux and the expression of abca1. inhibiting jak/stat activation by its specific inhibitor ag-490 or by sirna could also block aopps action on thp-1 cells. conclusions: aopps may first down-regulate the expression of lxrα and abca1 through jak/ stat signal pathway activation and then inhibit cholesterol efflux in thp-1-derived foam-like cells; therefore,our study may be useful for understanding the critical effects of aopps on the pathogenesis of atherosclerosis.
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کلیدواژه
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Advanced oxidation protein products; ATP-binding cassette transporter A1; Cholesterol efflux; JAK/STAT
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آدرس
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institute of cardiovascular research,key laboratory for atherosclerology of hunan province,life science research center,university of south china,hengyang 421001, China, institute of cardiovascular research,key laboratory for atherosclerology of hunan province,life science research center,university of south china,hengyang 421001, China, institute of cardiovascular research,key laboratory for atherosclerology of hunan province,life science research center,university of south china,hengyang 421001, China, institute of cardiovascular research,key laboratory for atherosclerology of hunan province,life science research center,university of south china,hengyang 421001, China, institute of cardiovascular research,key laboratory for atherosclerology of hunan province,life science research center,university of south china,hengyang 421001, China, institute of cardiovascular research,key laboratory for atherosclerology of hunan province,life science research center,university of south china,hengyang 421001, China, institute of cardiovascular research,key laboratory for atherosclerology of hunan province,life science research center,university of south china,hengyang 421001, China, institute of cardiovascular research,key laboratory for atherosclerology of hunan province,life science research center,university of south china,hengyang 421001, China, division of stem cell regulation and application,state key laboratory of chinese medicine powder and medicine innovation in hunan(incubation),hunan university of chinese medicine,changsha, China, institute of cardiovascular research,key laboratory for atherosclerology of hunan province,life science research center,university of south china,hengyang 421001, China
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Authors
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