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Lipoprotein-associated phospholipase A2 regulates macrophage apoptosis via the Akt and caspase-7 pathways
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نویسنده
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maeda t. ,takeuchi k. ,xiaoling p. ,zankov d.p. ,takashima n. ,fujiyoshi a. ,kadowaki t. ,miura k. ,ueshima h. ,ogita h.
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منبع
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journal of atherosclerosis and thrombosis - 2014 - دوره : 21 - شماره : 8 - صفحه:839 -853
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چکیده
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Aim: mutations in lipoprotein-associated phospholipase a2 (lp-pla2) are related to atherosclerosis. however,the molecular effects of lp-pla2 on atherosclerosis have not been fully investigated. therefore,this study attempted to elucidate this issue.methods: monocytes were isolated from randomly selected healthy male volunteers according to each lp-pla2 genotype (wild-type lp-pla2 [lp-pla2 (v/v)],the heterozygous v279f mutation [lp-pla2 (v/f)] and the homozygous v279f mutation [lp-pla2 (f/f)]) and differentiated into macrophages. the level of apoptosis in the macrophages following incubation without serum was measured using the annexin v/propidium iodide double staining method,and the underlying mechanisms were further examined using a culture cell line.results: the average plasma lp-pla2 concentration [lp-pla2 (v/v): 129.4 ng/ml,lp-pla2 (v/ f): 70.7 ng/ml,lp-pla2 (f/f): 0.4 ng/ml] and activity [lp-pla2 (v/v): 164.3 nmol/min/ml,lp-pla2 (v/f): 100.9 nmol/min/ml,lp-pla2 (f/f): 11.6 nmol/min/ml] were significantly different between each genotype,although the basic clinical characteristics were similar. the percentage of apoptotic cells was significantly higher among the lp-pla2 (f/f) macrophages compared with that observed in the lp-pla2 (v/v) macrophages. this induction of apoptosis was independent of the actions of acetylated low-density lipoproteins. in addition,the transfection of the expression plasmid of v279f mutant lp-pla2 into cos-7 cells or monocyte/macrophage-like u937 cells promoted apoptosis. the knockdown of lp-pla2 also increased the number of apoptotic cells. among the cells expressing mutant lp-pla2,the caspase-7 activity was increased,while the activated akt level was decreased.conclusions: the v279f mutation of lp-pla2 positively regulates the induction of apoptosis in macrophages and cos-7 cells. an increase in the caspase-7 activity and a reduction in the activated akt level are likely to be involved in this phenomenon. © 2014 japan atherosclerosis society.
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کلیدواژه
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Apoptosis; Atherosclerosis; Macrophage; Phospholipase
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آدرس
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division of molecular medical biochemistry,department of biochemistry and molecular biology,shiga university of medical scienceshiga, Japan, division of molecular medical biochemistry,department of biochemistry and molecular biology,shiga university of medical scienceshiga, Japan, division of molecular medical biochemistry,department of biochemistry and molecular biology,shiga university of medical scienceshiga, Japan, division of molecular medical biochemistry,department of biochemistry and molecular biology,shiga university of medical scienceshiga, Japan, department of health science,shiga university of medical scienceshiga, Japan, department of health science,shiga university of medical scienceshiga, Japan, department of health science,shiga university of medical scienceshiga, Japan, department of health science,shiga university of medical scienceshiga,japan,center for epidemiologic research in asia,shiga university of medical scienceshiga, Japan, department of health science,shiga university of medical scienceshiga,japan,center for epidemiologic research in asia,shiga university of medical scienceshiga, Japan, division of molecular medical biochemistry,department of biochemistry and molecular biology,shiga university of medical scienceshiga, Japan
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