Free cholesterol accumulation impairs antioxidant activities and aggravates apoptotic cell death in menadione-induced oxidative injury

► Free cholesterol accumulation increases menadione-induced superoxide and NO productions. ► Free cholesterol accumulation reduces antioxidant activities. ► Free cholesterol accumulation increases menadione-induced apoptosis. Although the relationship between hypercholesterolemia and oxidative stres...

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Veröffentlicht in:Archives of biochemistry and biophysics 2011-10, Vol.514 (1), p.57-67
Hauptverfasser: Lee, Waisin, Xu, Mingjing, Li, Yue, Gu, Yong, Chen, Jianping, Wong, Derek, Fung, Peter C.W., Shen, Jiangang
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container_issue 1
container_start_page 57
container_title Archives of biochemistry and biophysics
container_volume 514
creator Lee, Waisin
Xu, Mingjing
Li, Yue
Gu, Yong
Chen, Jianping
Wong, Derek
Fung, Peter C.W.
Shen, Jiangang
description ► Free cholesterol accumulation increases menadione-induced superoxide and NO productions. ► Free cholesterol accumulation reduces antioxidant activities. ► Free cholesterol accumulation increases menadione-induced apoptosis. 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.
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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. 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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.</description><subject>animal ovaries</subject><subject>Animals</subject><subject>antioxidant activity</subject><subject>Antioxidants - metabolism</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>catalase</subject><subject>Chinese hamsters</subject><subject>CHO Cells</subject><subject>Cholesterol</subject><subject>Cholesterol - genetics</subject><subject>Cholesterol - metabolism</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>endothelial nitric oxide synthase</subject><subject>Gene Expression Regulation</subject><subject>glutathione peroxidase</subject><subject>hypercholesterolemia</subject><subject>inducible nitric oxide synthase</subject><subject>menadione</subject><subject>Mutation</subject><subject>NADP (coenzyme)</subject><subject>NADPH Oxidases - genetics</subject><subject>Nitric oxide</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide Synthase Type II - genetics</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Superoxide</subject><subject>superoxide anion</subject><subject>superoxide dismutase</subject><subject>Superoxide Dismutase - genetics</subject><subject>Superoxides - metabolism</subject><subject>Vitamin K 3 - adverse effects</subject><subject>Vitamins - adverse effects</subject><issn>0003-9861</issn><issn>1096-0384</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1u1TAQhS1ERS-FB2AD3rFKOo7zK1aoooBUiUXbteXYk1tfJXGwnav2BXhuJtzCktVoPOccz3yMvROQCxD15SHXfZ8XIEQOTQ6ifMF2Aro6A9mWL9kOAGTWtbU4Z69jPAAJy7p4xc4L0ZayAtixX9cBkZsHP2JMGPzItTHrtI46OT9zNy3ahcj1TO2js1RJkNzRJYfbs-V6vw_6qNPWLn5JPjnDDY4jt6jTA3czn3DWluIwc7NdDVr-J4tikMaHNTy9YWeDHiO-fa4X7P76y93Vt-zmx9fvV59vMiObOmVagm46Y2RVlboybdN0vayEFVaLFgsreijoXqwGrGQ91KIyTQlFPTRgZI1SXrCPp9wl-J8rnawmF7dl9Yx-japtu7IqiCgpxUlpgo8x4KCW4CYdnpQAtdFXB0X01UZfQaOIPnneP6ev_YT2n-MvbhJ8OAkG7ZXeBxfV_S0l0Kwgf7l9--mkQKJwdBhUNA5nYuYCmqSsd_9Z4Deh7aDx</recordid><startdate>20111001</startdate><enddate>20111001</enddate><creator>Lee, Waisin</creator><creator>Xu, Mingjing</creator><creator>Li, Yue</creator><creator>Gu, Yong</creator><creator>Chen, Jianping</creator><creator>Wong, Derek</creator><creator>Fung, Peter C.W.</creator><creator>Shen, Jiangang</creator><general>Elsevier Inc</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20111001</creationdate><title>Free cholesterol accumulation impairs antioxidant activities and aggravates apoptotic cell death in menadione-induced oxidative injury</title><author>Lee, Waisin ; 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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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21843500</pmid><doi>10.1016/j.abb.2011.07.014</doi><tpages>11</tpages></addata></record>
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subjects animal ovaries
Animals
antioxidant activity
Antioxidants - metabolism
Apoptosis
Apoptosis - drug effects
catalase
Chinese hamsters
CHO Cells
Cholesterol
Cholesterol - genetics
Cholesterol - metabolism
Cricetinae
Cricetulus
endothelial nitric oxide synthase
Gene Expression Regulation
glutathione peroxidase
hypercholesterolemia
inducible nitric oxide synthase
menadione
Mutation
NADP (coenzyme)
NADPH Oxidases - genetics
Nitric oxide
Nitric Oxide - metabolism
Nitric Oxide Synthase Type II - genetics
Oxidative stress
Oxidative Stress - drug effects
Reactive Oxygen Species - metabolism
Superoxide
superoxide anion
superoxide dismutase
Superoxide Dismutase - genetics
Superoxides - metabolism
Vitamin K 3 - adverse effects
Vitamins - adverse effects
title Free cholesterol accumulation impairs antioxidant activities and aggravates apoptotic cell death in menadione-induced oxidative injury
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