Increased sensitivity of apolipoprotein E knockout mice to copper-induced oxidative injury to the liver.
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.
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.
Yuan
Y
Chen
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.
Bin
B
Li
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.
Ran-ran
RR
Zhao
Department of Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 057100, PR China.
Hui-feng
HF
Zhang
Key Laboratory of Neurology of Hebei Province, Shijiazhuang, Hebei 057100, PR China.
Chao
C
Zhen
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.
Li
L
Guo
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000235:genetics / Q000378:metabolism*; D003300:Copper / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D000975:Antioxidants; D001057:Apolipoproteins E; D008565:Membrane Proteins; D017392:Thiobarbituric Acid Reactive Substances; D003300:Copper; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D013482:Superoxide Dismutase; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse
Apolipoprotein E; Copper; Hepatolenticular degeneration; Oxidative stress; Wilson's disease