title: Erythrocyte copper chaperone for superoxide dismutase and superoxide dismutase as biomarkers for hepatic copper concentrations in Labrador retrievers.
abstract: Hereditary hepatic copper accumulation in Labrador retrievers leads to hepatitis with fibrosis and eventually cirrhosis. The development of a non-invasive blood-based biomarker for copper status in dogs could be helpful in identifying dogs at risk and to monitor copper concentrations during treatment. In this study, two cellular copper metabolism proteins, Cu/Zn superoxide dismutase (SOD1) and its chaperone (copper chaperone for SOD1, CCS) were measured in erythrocytes and tested for association with hepatic copper concentrations in 15 Labrador retrievers with normal or increased hepatic copper concentrations. Antibodies against CCS and SOD1 were applicable for use in canine specimens. This was demonstrated by the loss of immune-reactive bands for CCS and SOD1 in siRNA treated canine bile duct epithelial cells. Erythrocyte CCS and CCS/SOD1 ratios were decreased 2.37 (P <0.001) and 3.29 (P <0.001) fold in the high copper group compared to the normal copper group. Erythrocyte CCS and CCS/SOD1 ratio are potential new biomarkers for hepatic copper concentrations in Labrador retrievers and could facilitate early diagnosis and treatment monitoring for copper-associated hepatitis in dogs.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, Utrecht 3584 CM, Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Dirksen
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, Utrecht 3584 CM, Netherlands.
authors.forename: Y S
authors.initials: YS
authors.lastname: Roelen
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, Utrecht 3584 CM, Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: van Wolferen
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, Utrecht 3584 CM, Netherlands.
authors.forename: H S
authors.initials: HS
authors.lastname: Kruitwagen
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, Utrecht 3584 CM, Netherlands.
authors.forename: L C
authors.initials: LC
authors.lastname: Penning
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, Utrecht 3584 CM, Netherlands.
authors.forename: I A
authors.initials: IA
authors.lastname: Burgener
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, Utrecht 3584 CM, Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Spee
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, Utrecht 3584 CM, Netherlands. Electronic address: h.fieten@uu.nl.
authors.forename: H
authors.initials: H
authors.lastname: Fieten
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D003300:Copper / Q000097:blood* / Q000378:metabolism; D004285:Dogs / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D018832:Molecular Chaperones / Q000097:blood* / Q000378:metabolism; D000072105:Superoxide Dismutase-1 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018832:Molecular Chaperones; D003300:Copper; D000072105:Superoxide Dismutase-1
keywords: Biomarker; Copper; Copper chaperone for superoxide Cu/Zn dismutase 1; Hepatitis; Superoxide dismutase 1