title: Quercetin protects RAW264.7 macrophages from glucosamine-induced apoptosis and lipid accumulation via the endoplasmic reticulum stress pathway.
abstract: It is increasingly recognized that macrophages are a key cell in the development of atherosclerosis. Glucosamine, the product of the hexosamine biosynthetic pathway in diabetes mellitus, can disturb lipid metabolism, induce apoptosis and accelerate atherosclerosis via endoplasmic reticulum (ER) stress in various types of cells. Previous studies have indicated that quercetin possesses antidiabetic, anti‑oxidative, anti‑inflammatory and anti‑apoptotic activities as a flavonoid. Studies have also demonstrated its novel pharmacological properties for inhibiting ER stress. The present study focussed on the effects of quercetin on cell injury and ER stress in glucosamine‑induced macrophages. RAW264.7 macrophages were cultured with 15 mM glucosamine, following which the levels of apoptosis, intracellular total and free cholesterol, and apoptosis‑ and ER stress‑associated proteins were measured in the macrophages treated with or without quercetin. Additionally, the ratio of cholestryl ester/total cholesterol was calculated to observe the formation of foam cells. The results demonstrated that apoptosis and abnormal lipid accumulation in the RAW264.7 cells, which was induced by glucosamine, were significantly reversed by quercetin. In addition, quercetin treatment suppressed the increase of C/EBP homologous protein, and inhibited the activation of JNK and caspase‑12, which was induced by glucosamine. Quercetin also increased the expression level of full length activating transcriptional factor 6 and decreased the expression of glucose regulated protein 78. Of note, the beneficial effects of quercetin on the glucosamine‑induced RAW264.7 cells were reversed by treatment with tunicamycin. These findings suggest that quercetin may have properties to prevent glucosamine‑induced apoptosis and lipid accumulation via the ER stress pathway in RAW264.7 macrophages.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, P.R. China.
authors.forename: Xiaxia
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Clinical Nutrition, Peking University International Hospital, Beijing 102206, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, P.R. China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, P.R. China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing 100191, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D050197:Atherosclerosis / Q000188:drug therapy; D053454:Caspase 12 / Q000378:metabolism; D048909:Diabetes Complications / Q000188:drug therapy; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D005944:Glucosamine / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D011794:Quercetin / Q000494:pharmacology*; D000067996:RAW 264.7 Cells; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D051702:Activating Transcription Factor 6; C497112:Atf6 protein, mouse; C497250:Ddit3 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D051742:Transcription Factor CHOP; D011794:Quercetin; D048670:MAP Kinase Kinase 4; C506440:Casp12 protein, mouse; D053454:Caspase 12; D005944:Glucosamine