The relationship between copper and steatosis in Wilson's disease

Liggi, Mauro; Murgia, Debora; Civolani, Alberto; Demelia, Enrico; Sorbello, Orazio; Demelia, Luigi

doi:10.1016/j.clinre.2012.03.038

Cited by 41 publications

(26 citation statements)

References 39 publications

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“…In addition, higher copper levels were observed in severe steatosis compared to mild and moderate steatosis. 16 The study confirmed the idea that steatosis in WD is not related to the metabolic syndrome but to copper accumulation itself. Interestingly, murine models of WD, including the copper transporter ATP7B knockout mouse and the toxic-milk mouse, presented downregulation of transcript levels of genes involved in lipid metabolism including SREBP-1c, FAS, and peroxisome proliferator-activated receptor-a (PPAR-a).…”

Section: What Is the Relation Between Copper Excess And Hepatic Steatsupporting

confidence: 77%

The Evolving Scenario of Copper and Fatty Liver

Medici

2013

Metabolic Syndrome and Related Disorders

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Section: What Is the Relation Between Copper Excess And Hepatic Steatsupporting

confidence: 77%

The Evolving Scenario of Copper and Fatty Liver

Medici

2013

Metabolic Syndrome and Related Disorders

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“…A liver-specific ATP7B knockout mouse develops lipid dysregulation without inflammation, suggesting that metabolic symptoms may be directly linked to copper levels and not a secondary symptom of liver inflammation observed in Wilson disease (89). Consistent with dietary and genetic studies linking long-term changes in copper to changes in fat metabolism (90,91), work from our laboratory identified copper as a newly recognized allosteric regulator of phosphodiesterase 3B (PDE3B), a phosphodiesterase that controls lipolysis in adipocytes (92). Lipolysis, the breakdown of triglycerides into glycerol and fatty acids, may be induced in tissues and cells by treatment with isoproterenol, which stimulates the betaadrenergic receptor and induces a signaling cascade mediated by the second messenger cyclicadenosine monophosphate (cAMP).…”

Section: Copper Regulation Of Fat Metabolismmentioning

confidence: 51%

Copper signaling in the brain and beyond

Ackerman

Chang

2018

Journal of Biological Chemistry

150

124

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Transition metals have been recognized and studied primarily in the context of their essential roles as structural and metabolic cofactors for biomolecules that compose living systems. More recently, an emerging paradigm of transition metal signaling, where dynamic changes in transition metal pools can modulate protein function, cell fate, and organism health and disease, has broadened our view of the potential contributions of these essential nutrients in biology. Using copper as a canonical example of transition metal signaling, we highlight key experiments where direct measurement and/or visualization of dynamic copper pools, in combination with biochemical, physiological, and behavioral studies, have deciphered sources, targets, and physiological effects of copper signals.

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“…Cells were maintained in a humidified incubator at 37°C with 5% CO 2 . Copper overload of the control HepG2 cells was achieved by treatment with 10 μM, 200 μM and 500 μM copper sulfate (Sigma, St Louis, MO, USA) in the media for 8h and 24h respectively These doses were chosen on the basis of reported data both in HepG2 cells (10) and in WD patients (11). During incubation with copper sulfate (Sigma, St Louis, MO, USA) cells were grown in minimum essential medium supplemented with L-glutamine.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Copper excess in liver HepG2 cells interferes with apoptosis and lipid metabolic signaling at the protein level

Liu¹,

Yang²,

Song³

et al. 2015

Turk J Gastroenterol

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Background/Aims: 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. Materials and Methods: 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.Results: The results demonstrate dose-and time-dependent cell viability and apoptosis in HepG2 cells following treatment with 10μM , 200μM and 500μM of copper sulfate for 8 and 24 h. Copper overload significantly induced the expression of HSPA1A (heat shock 70kDa protein 1A), an oxidative stress-responsive signal gene, and BAG3 (BCL2 associated athanogene3), an anti-apoptotic gene, while expression of HMGCR (3-hydroxy-3-methylglutarylCoA reductase), a lipid biosynthesis and lipid metabolism gene, was inhibited. Conclusion: 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.

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The relationship between copper and steatosis in Wilson's disease

Cited by 41 publications

References 39 publications

The Evolving Scenario of Copper and Fatty Liver

The Evolving Scenario of Copper and Fatty Liver

Copper signaling in the brain and beyond

Copper excess in liver HepG2 cells interferes with apoptosis and lipid metabolic signaling at the protein level

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