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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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. |
doi_str_mv | 10.1016/j.abb.2011.07.014 |
format | Article |
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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><identifier>ISSN: 0003-9861</identifier><identifier>EISSN: 1096-0384</identifier><identifier>DOI: 10.1016/j.abb.2011.07.014</identifier><identifier>PMID: 21843500</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>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</subject><ispartof>Archives of biochemistry and biophysics, 2011-10, Vol.514 (1), p.57-67</ispartof><rights>2011 Elsevier Inc.</rights><rights>Copyright © 2011 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c376t-a30a79cc3554a5c8779b351d1da18e2d1b02986e5fe536f615c74026f70c36e33</citedby><cites>FETCH-LOGICAL-c376t-a30a79cc3554a5c8779b351d1da18e2d1b02986e5fe536f615c74026f70c36e33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0003986111002669$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21843500$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Waisin</creatorcontrib><creatorcontrib>Xu, Mingjing</creatorcontrib><creatorcontrib>Li, Yue</creatorcontrib><creatorcontrib>Gu, Yong</creatorcontrib><creatorcontrib>Chen, Jianping</creatorcontrib><creatorcontrib>Wong, Derek</creatorcontrib><creatorcontrib>Fung, Peter C.W.</creatorcontrib><creatorcontrib>Shen, Jiangang</creatorcontrib><title>Free cholesterol accumulation impairs antioxidant activities and aggravates apoptotic cell death in menadione-induced oxidative injury</title><title>Archives of biochemistry and biophysics</title><addtitle>Arch Biochem Biophys</addtitle><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.</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 ; Xu, Mingjing ; Li, Yue ; Gu, Yong ; Chen, Jianping ; Wong, Derek ; Fung, Peter C.W. ; Shen, Jiangang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c376t-a30a79cc3554a5c8779b351d1da18e2d1b02986e5fe536f615c74026f70c36e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>animal ovaries</topic><topic>Animals</topic><topic>antioxidant activity</topic><topic>Antioxidants - metabolism</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>catalase</topic><topic>Chinese hamsters</topic><topic>CHO Cells</topic><topic>Cholesterol</topic><topic>Cholesterol - genetics</topic><topic>Cholesterol - metabolism</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>endothelial nitric oxide synthase</topic><topic>Gene Expression Regulation</topic><topic>glutathione peroxidase</topic><topic>hypercholesterolemia</topic><topic>inducible nitric oxide synthase</topic><topic>menadione</topic><topic>Mutation</topic><topic>NADP (coenzyme)</topic><topic>NADPH Oxidases - genetics</topic><topic>Nitric oxide</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Synthase Type II - genetics</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Superoxide</topic><topic>superoxide anion</topic><topic>superoxide dismutase</topic><topic>Superoxide Dismutase - genetics</topic><topic>Superoxides - metabolism</topic><topic>Vitamin K 3 - adverse effects</topic><topic>Vitamins - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, Waisin</creatorcontrib><creatorcontrib>Xu, Mingjing</creatorcontrib><creatorcontrib>Li, Yue</creatorcontrib><creatorcontrib>Gu, Yong</creatorcontrib><creatorcontrib>Chen, Jianping</creatorcontrib><creatorcontrib>Wong, Derek</creatorcontrib><creatorcontrib>Fung, Peter C.W.</creatorcontrib><creatorcontrib>Shen, Jiangang</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Archives of biochemistry and biophysics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, Waisin</au><au>Xu, Mingjing</au><au>Li, Yue</au><au>Gu, Yong</au><au>Chen, Jianping</au><au>Wong, Derek</au><au>Fung, Peter C.W.</au><au>Shen, Jiangang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Free cholesterol accumulation impairs antioxidant activities and aggravates apoptotic cell death in menadione-induced oxidative injury</atitle><jtitle>Archives of biochemistry and biophysics</jtitle><addtitle>Arch Biochem Biophys</addtitle><date>2011-10-01</date><risdate>2011</risdate><volume>514</volume><issue>1</issue><spage>57</spage><epage>67</epage><pages>57-67</pages><issn>0003-9861</issn><eissn>1096-0384</eissn><abstract>► 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.</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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