Copper excess in liver HepG2 cells interferes with apoptosis and lipid metabolic signaling at the protein level
Copper is an essential trace element that serves as an important catalytic cofactor for cuproenzymes, carrying out major biological functions in growth and development. Although Wilson's disease (WD) is unquestionably caused by mutations in the ATP7B gene and subsequent copper overload, the pre...
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Veröffentlicht in: | The Turkish journal of gastroenterology 2014-12, Vol.25 Suppl 1 (1), p.116-121 |
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container_title | The Turkish journal of gastroenterology |
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creator | Liu, Yu Yang, Huarong Song, Zhi Gu, Shaojuan |
description | Copper is an essential trace element that serves as an important catalytic cofactor for cuproenzymes, carrying out major biological functions in growth and development. Although Wilson's disease (WD) is unquestionably caused by mutations in the ATP7B gene and subsequent copper overload, the precise role of copper in inducing pathological changes remains poorly understood.
Our study aimed to explore, in HepG2 cells exposed to copper, the cell viability and apoptotic cells was tested by MTT and Hoechst 33342 stainning respectively, and the signaling pathways involved in oxidative stress response, apoptosis and lipid metabolism were determined by real time RT-PCR and Western blot analysis.
The results demonstrate dose- and time-dependent cell viability and apoptosis in HepG2 cells following treatment with 10 μM, 200 μM and 500 μM of copper sulfate for 8 and 24 h. Copper overload significantly induced the expression of HSPA1A (heat shock 70 kDa protein 1A), an oxidative stress-responsive signal gene, and BAG3 (BCL2 associated athanogene3), an anti-apoptotic gene, while expression of HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase), a lipid biosynthesis and lipid metabolism gene, was inhibited.
These findings provide new insights into possible mechanisms accounting for the development of liver apoptosis and steatosis in the early stages of Wilson's disease. |
doi_str_mv | 10.5152/tjg.2014.5064 |
format | Article |
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Our study aimed to explore, in HepG2 cells exposed to copper, the cell viability and apoptotic cells was tested by MTT and Hoechst 33342 stainning respectively, and the signaling pathways involved in oxidative stress response, apoptosis and lipid metabolism were determined by real time RT-PCR and Western blot analysis.
The results demonstrate dose- and time-dependent cell viability and apoptosis in HepG2 cells following treatment with 10 μM, 200 μM and 500 μM of copper sulfate for 8 and 24 h. Copper overload significantly induced the expression of HSPA1A (heat shock 70 kDa protein 1A), an oxidative stress-responsive signal gene, and BAG3 (BCL2 associated athanogene3), an anti-apoptotic gene, while expression of HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase), a lipid biosynthesis and lipid metabolism gene, was inhibited.
These findings provide new insights into possible mechanisms accounting for the development of liver apoptosis and steatosis in the early stages of Wilson's disease.</description><identifier>ISSN: 1300-4948</identifier><identifier>EISSN: 2148-5607</identifier><identifier>DOI: 10.5152/tjg.2014.5064</identifier><identifier>PMID: 25910288</identifier><language>eng</language><publisher>Turkey</publisher><subject>Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Apoptosis - drug effects ; Apoptosis Regulatory Proteins - genetics ; Apoptosis Regulatory Proteins - metabolism ; Cell Survival - drug effects ; Copper Sulfate - pharmacology ; Dose-Response Relationship, Drug ; Hep G2 Cells - drug effects ; Hep G2 Cells - metabolism ; HSP70 Heat-Shock Proteins - genetics ; HSP70 Heat-Shock Proteins - metabolism ; Humans ; Hydroxymethylglutaryl CoA Reductases - genetics ; Hydroxymethylglutaryl CoA Reductases - metabolism ; Lipid Metabolism - drug effects ; Oxidative Stress ; RNA, Messenger - metabolism ; Signal Transduction - drug effects</subject><ispartof>The Turkish journal of gastroenterology, 2014-12, Vol.25 Suppl 1 (1), p.116-121</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c293t-5f79866fe24f346cdc574fff27aa4ee0b975b072fd588b3bf8a417dd49ae46e33</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25910288$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Yang, Huarong</creatorcontrib><creatorcontrib>Song, Zhi</creatorcontrib><creatorcontrib>Gu, Shaojuan</creatorcontrib><title>Copper excess in liver HepG2 cells interferes with apoptosis and lipid metabolic signaling at the protein level</title><title>The Turkish journal of gastroenterology</title><addtitle>Turk J Gastroenterol</addtitle><description>Copper is an essential trace element that serves as an important catalytic cofactor for cuproenzymes, carrying out major biological functions in growth and development. Although Wilson's disease (WD) is unquestionably caused by mutations in the ATP7B gene and subsequent copper overload, the precise role of copper in inducing pathological changes remains poorly understood.
Our study aimed to explore, in HepG2 cells exposed to copper, the cell viability and apoptotic cells was tested by MTT and Hoechst 33342 stainning respectively, and the signaling pathways involved in oxidative stress response, apoptosis and lipid metabolism were determined by real time RT-PCR and Western blot analysis.
The results demonstrate dose- and time-dependent cell viability and apoptosis in HepG2 cells following treatment with 10 μM, 200 μM and 500 μM of copper sulfate for 8 and 24 h. Copper overload significantly induced the expression of HSPA1A (heat shock 70 kDa protein 1A), an oxidative stress-responsive signal gene, and BAG3 (BCL2 associated athanogene3), an anti-apoptotic gene, while expression of HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase), a lipid biosynthesis and lipid metabolism gene, was inhibited.
These findings provide new insights into possible mechanisms accounting for the development of liver apoptosis and steatosis in the early stages of Wilson's disease.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Cell Survival - drug effects</subject><subject>Copper Sulfate - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Hep G2 Cells - drug effects</subject><subject>Hep G2 Cells - metabolism</subject><subject>HSP70 Heat-Shock Proteins - genetics</subject><subject>HSP70 Heat-Shock Proteins - metabolism</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl CoA Reductases - genetics</subject><subject>Hydroxymethylglutaryl CoA Reductases - metabolism</subject><subject>Lipid Metabolism - drug effects</subject><subject>Oxidative Stress</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction - drug effects</subject><issn>1300-4948</issn><issn>2148-5607</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kD1PwzAQhi0EoqUwsiKPLCn-jJ0RVdAiVWKB2XKSc-sqTUzs8vHvSdTCdHpPj97TPQjdUjKXVLKHtNvMGaFiLkkuztCUUaEzmRN1jqaUE5KJQugJuopxRwjXNGeXaMJkQQnTeoq6RRcC9Bi-K4gR-xY3_nPIKwhLhitomnGZoHfQQ8RfPm2xDV1IXfQR27Ye-OBrvIdky67xFY5-09rGtxtsE05bwKHvEozF8AnNNbpwtolwc5oz9P789LZYZevX5cvicZ1VrOApk04VOs8dMOG4yKu6kko455iyVgCQslCyJIq5Wmpd8tJpK6iqa1FYEDlwPkP3x97h-scBYjJ7H8d3bAvdIRqaK8UVk7oY0OyIVn0XYw_OhN7vbf9jKDGjYzM4NqNjMzoe-LtT9aHcQ_1P_0nlv4gieXY</recordid><startdate>20141201</startdate><enddate>20141201</enddate><creator>Liu, Yu</creator><creator>Yang, Huarong</creator><creator>Song, Zhi</creator><creator>Gu, Shaojuan</creator><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>20141201</creationdate><title>Copper excess in liver HepG2 cells interferes with apoptosis and lipid metabolic signaling at the protein level</title><author>Liu, Yu ; Yang, Huarong ; Song, Zhi ; Gu, Shaojuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c293t-5f79866fe24f346cdc574fff27aa4ee0b975b072fd588b3bf8a417dd49ae46e33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis Regulatory Proteins - genetics</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Cell Survival - drug effects</topic><topic>Copper Sulfate - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Hep G2 Cells - drug effects</topic><topic>Hep G2 Cells - metabolism</topic><topic>HSP70 Heat-Shock Proteins - genetics</topic><topic>HSP70 Heat-Shock Proteins - metabolism</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl CoA Reductases - genetics</topic><topic>Hydroxymethylglutaryl CoA Reductases - metabolism</topic><topic>Lipid Metabolism - drug effects</topic><topic>Oxidative Stress</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Yang, Huarong</creatorcontrib><creatorcontrib>Song, Zhi</creatorcontrib><creatorcontrib>Gu, Shaojuan</creatorcontrib><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>The Turkish journal of gastroenterology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Yu</au><au>Yang, Huarong</au><au>Song, Zhi</au><au>Gu, Shaojuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Copper excess in liver HepG2 cells interferes with apoptosis and lipid metabolic signaling at the protein level</atitle><jtitle>The Turkish journal of gastroenterology</jtitle><addtitle>Turk J Gastroenterol</addtitle><date>2014-12-01</date><risdate>2014</risdate><volume>25 Suppl 1</volume><issue>1</issue><spage>116</spage><epage>121</epage><pages>116-121</pages><issn>1300-4948</issn><eissn>2148-5607</eissn><abstract>Copper is an essential trace element that serves as an important catalytic cofactor for cuproenzymes, carrying out major biological functions in growth and development. Although Wilson's disease (WD) is unquestionably caused by mutations in the ATP7B gene and subsequent copper overload, the precise role of copper in inducing pathological changes remains poorly understood.
Our study aimed to explore, in HepG2 cells exposed to copper, the cell viability and apoptotic cells was tested by MTT and Hoechst 33342 stainning respectively, and the signaling pathways involved in oxidative stress response, apoptosis and lipid metabolism were determined by real time RT-PCR and Western blot analysis.
The results demonstrate dose- and time-dependent cell viability and apoptosis in HepG2 cells following treatment with 10 μM, 200 μM and 500 μM of copper sulfate for 8 and 24 h. Copper overload significantly induced the expression of HSPA1A (heat shock 70 kDa protein 1A), an oxidative stress-responsive signal gene, and BAG3 (BCL2 associated athanogene3), an anti-apoptotic gene, while expression of HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase), a lipid biosynthesis and lipid metabolism gene, was inhibited.
These findings provide new insights into possible mechanisms accounting for the development of liver apoptosis and steatosis in the early stages of Wilson's disease.</abstract><cop>Turkey</cop><pmid>25910288</pmid><doi>10.5152/tjg.2014.5064</doi><tpages>6</tpages></addata></record> |
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source | MEDLINE; EZB-FREE-00999 freely available EZB journals |
subjects | Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Apoptosis - drug effects Apoptosis Regulatory Proteins - genetics Apoptosis Regulatory Proteins - metabolism Cell Survival - drug effects Copper Sulfate - pharmacology Dose-Response Relationship, Drug Hep G2 Cells - drug effects Hep G2 Cells - metabolism HSP70 Heat-Shock Proteins - genetics HSP70 Heat-Shock Proteins - metabolism Humans Hydroxymethylglutaryl CoA Reductases - genetics Hydroxymethylglutaryl CoA Reductases - metabolism Lipid Metabolism - drug effects Oxidative Stress RNA, Messenger - metabolism Signal Transduction - drug effects |
title | Copper excess in liver HepG2 cells interferes with apoptosis and lipid metabolic signaling at the protein level |
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