title: Ceruloplasmin protects against rotenone-induced oxidative stress and neurotoxicity.
abstract: To clarify the neuroprotective property of ceruloplasmin and the pathogenesis of aceruloplasminemia, we generated ceruloplasmin-deficient (CP⁻/⁻) mice on the C57BL/10 genetic background and further treated them with a mitochondrial complex I inhibitor, rotenone. There was no iron accumulation in the brains of CP⁻/⁻ mice at least up to 60 weeks of age. Without rotenone treatment, CP⁻/⁻ mice showed slight motor dysfunction compared with CP⁺/⁺ mice, but there were no detectable differences in the levels of oxidative stress markers between these two groups. A low dose of rotenone did not affect the mitochondrial complex I activity in our mice, however, it caused a significant change in motor behavior, neuropathology, or the levels of oxidative stress markers in CP⁻/⁻ mice, but not in CP⁺/⁺ mice. Our data support that ceruloplasmin protects against rotenone-induced oxidative stress and neurotoxicity, probably through its antioxidant properties independently of its function of iron metabolism.
authors.affiliation: Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
authors.forename: Akiyo
authors.initials: A
authors.lastname: Hineno
authors.forename: Kazuma
authors.initials: K
authors.lastname: Kaneko
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Yoshida
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Ikeda
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002570:Ceruloplasmin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects*; D012402:Rotenone / Q000494:pharmacology*
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D012402:Rotenone; D002570:Ceruloplasmin; D042967:Electron Transport Complex I; C027576:4-hydroxy-2-nonenal