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Activating transcription factor 6 mediates oxidized LDL-induced cholesterol accumulation and apoptosis in macrophages by up-regulating chop expression
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نویسنده
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yao s. ,zong c. ,zhang y. ,sang h. ,yang m. ,jiao p. ,fang y. ,yang n. ,song g. ,qin s.
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منبع
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journal of atherosclerosis and thrombosis - 2013 - دوره : 20 - شماره : 1 - صفحه:94 -107
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چکیده
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Aim: this study was to explore whether activating transcription factor 6 (atf6),an important sensor to endoplasmic reticulum (er) stress,would mediate oxidized low-density lipoprotein (ox-ldl) - induced cholesterol accumulation and apoptosis in cultured macrophages and the underlying molecular mechanisms. methods: intracellular lipid droplets and total cholesterol levels were assayed by oil red o staining and enzymatic colorimetry,respectively. cell viability and apoptosis were determined using mtt assay and annexinv-fitc apoptosis detection kit,respectively. the nuclear translocation of atf6 in cells was detected by immunofluorescence analysis. protein and mrna levels were examined by western blot analysis and real time-pcr,respectively. atf6 sirna was transfected to raw264.7 cells by lipofectamin. results: exposure of cells to ox-ldl induced glucose-regulated protein 78 (grp78). c/ebp homologous protein (chop),a key-signaling component of er stress-induced apoptosis,was up-regulated in ox-ldl-treated cells. atf6,a factor that positively regulates chop expression,was activated by ox-ldl in a concentration- and time- dependent manner. the role of the atf6-mediated er stress pathway was further confirmed through the sirna-mediated knockdown of atf6,which attenuated ox-ldl-induced upregulation of chop,cholesterol accumulation and apoptosis in macrophages. in addition,the phosphorylation of double-stranded rna-activated protein kinase-like endoplasmic reticulum kinase (perk),another factor that positively regulates chop expression,was induced in the presence of ox-ldl,and perk-specific sirna also inhibited the ox-ldl-induced upregulation of chop and apoptosis in raw264.7 cells. conclusion: these results demonstrate that er stress-related proteins,particularly atf6 and its downstream molecule chop,are involved in ox-ldl-induced cholesterol accumulation and apoptosis in macrophages.
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کلیدواژه
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Activating transcription factor 6; Apoptosis; CHOP; Endoplasmic reticulum stress; Macrophage; Oxidized low-density lipoprotein
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آدرس
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institute of atherosclerosis,key laboratory of atherosclerosis in universities of shandong,taishan medical university,taian,china,college of basic medical sciences,taishan medical university,taian, China, institute of atherosclerosis,key laboratory of atherosclerosis in universities of shandong,taishan medical university,taian, China, institute of atherosclerosis,key laboratory of atherosclerosis in universities of shandong,taishan medical university,taian, China, institute of atherosclerosis,key laboratory of atherosclerosis in universities of shandong,taishan medical university,taian,china,college of basic medical sciences,taishan medical university,taian, China, institute of atherosclerosis,key laboratory of atherosclerosis in universities of shandong,taishan medical university,taian, China, institute of atherosclerosis,key laboratory of atherosclerosis in universities of shandong,taishan medical university,taian, China, college of basic medical sciences,taishan medical university,taian, China, institute of atherosclerosis,key laboratory of atherosclerosis in universities of shandong,taishan medical university,taian, China, institute of atherosclerosis,key laboratory of atherosclerosis in universities of shandong,taishan medical university,taian, China, institute of atherosclerosis,key laboratory of atherosclerosis in universities of shandong,taishan medical university,taian,china,college of basic medical sciences,taishan medical university,taian, China
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Authors
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