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
Hauptverfasser: Liu, Yu, Yang, Huarong, Song, Zhi, Gu, Shaojuan
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container_issue 1
container_start_page 116
container_title The Turkish journal of gastroenterology
container_volume 25 Suppl 1
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
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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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