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Biochem Biophys Res Commun. 2015 Apr 10;459(3):529-33. doi: 10.1016/j.bbrc.2015.02.143. Epub 2015 Mar 5.

Increased sensitivity of apolipoprotein E knockout mice to copper-induced oxidative injury to the liver.

Author information

1
Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 057100, PR China; Key Laboratory of Neurology of Hebei Province, Shijiazhuang, Hebei 057100, PR China. Electronic address: ychen74@163.com.
2
Key Laboratory of Neurology of Hebei Province, Shijiazhuang, Hebei 057100, PR China; Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 057100, PR China.
3
Key Laboratory of Neurology of Hebei Province, Shijiazhuang, Hebei 057100, PR China; Department of Emergency, The First Hospital of Handan, Handan, Hebei 056002, PR China.
4
Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 057100, PR China.
5
Key Laboratory of Neurology of Hebei Province, Shijiazhuang, Hebei 057100, PR China.
6
Key Laboratory of Neurology of Hebei Province, Shijiazhuang, Hebei 057100, PR China; Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 057100, PR China. Electronic address: guoli6@163.com.

Abstract

Apolipoprotein E (ApoE) genotypes are related to clinical presentations in patients with Wilson's disease, indicating that ApoE may play an important role in the disease. However, our understanding of the role of ApoE in Wilson's disease is limited. High copper concentration in Wilson's disease induces excessive generation of free oxygen radicals. Meanwhile, ApoE proteins possess antioxidant effects. We therefore determined whether copper-induced oxidative damage differ in the liver of wild-type and ApoE knockout (ApoE(-/-)) mice. Both wild-type and ApoE(-/-) mice were intragastrically administered with 0.2 mL of copper sulfate pentahydrate (200 mg/kg; a total dose of 4 mg/d) or the same volume of saline daily for 12 weeks, respectively. Copper and oxidative stress markers in the liver tissue and in the serum were assessed. Our results showed that, compared with the wild-type mice administered with copper, TBARS as a marker of lipid peroxidation, the expression of oxygenase-1 (HO-1), NAD(P)H dehydrogenase, and quinone 1 (NQO1) significantly increased in the ApoE(-/-) mice administered with copper, meanwhile superoxide dismutase (SOD) activity significantly decreased. Thus, it is concluded that ApoE may protect the liver from copper-induced oxidative damage in Wilson's disease.

KEYWORDS:

Apolipoprotein E; Copper; Hepatolenticular degeneration; Oxidative stress; Wilson's disease

PMID:
25749341
DOI:
10.1016/j.bbrc.2015.02.143
[Indexed for MEDLINE]

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