title: Free cholesterol accumulation impairs antioxidant activities and aggravates apoptotic cell death in menadione-induced oxidative injury.
abstract: Although the relationship between hypercholesterolemia and oxidative stress has been extensively investigated, direct evidence regarding to the roles of cholesterol accumulation in the generations of reactive oxygen species (ROS) and apoptotic cell death under oxidative stress is lack. In this study, we investigated productions of superoxide anions (O(2)(-)) and nitric oxide (NO), and apoptotic cell death in wild type Chinese hamster ovary (CHO) cells and cholesterol accumulated CHO cells genetically and chemically. Oxidative stress was induced by menadione challenge. The results revealed that abundance of free cholesterol (FC) promoted menadione-induced O(2)(-) and NO productions. FC accumulation down-regulated eNOS expression but up-regulated NADPH oxidases, and inhibited the activities of superoxide dismutase (SOD) and catalase. Treatment of menadione increased the expressions of iNOS and qp91 phox, enhanced the activities of SOD and catalase in the wild-type CHO cells but inhibited the activity of glutathione peroxidase in the cholesterol accumulated CHO cells. Moreover, FC abundance promoted apoptotic cell death in these cells. Taken together, those results suggest that free cholesterol accumulation aggravates menadione-induced oxidative stress and exacerbates apoptotic cell death.
authors.affiliation: School of Chinese Medicine, The University of Hong Kong, China.
authors.forename: Waisin
authors.initials: W
authors.lastname: Lee
authors.forename: Mingjing
authors.initials: M
authors.lastname: Xu
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.forename: Jianping
authors.initials: J
authors.lastname: Chen
authors.forename: Derek
authors.initials: D
authors.lastname: Wong
authors.forename: Peter C W
authors.initials: PC
authors.lastname: Fung
authors.forename: Jiangang
authors.initials: J
authors.lastname: Shen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D016466:CHO Cells; D002784:Cholesterol / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005786:Gene Expression Regulation; D009154:Mutation; D019255:NADPH Oxidases / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D013481:Superoxides / Q000378:metabolism*; D024483:Vitamin K 3 / Q000009:adverse effects; D014815:Vitamins / Q000009:adverse effects
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D014815:Vitamins; D013481:Superoxides; D009569:Nitric Oxide; D024483:Vitamin K 3; D002784:Cholesterol; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase; D019255:NADPH Oxidases