Increased vulnerability to rotenone-induced neurotoxicity in ceruloplasmin-deficient mice.
Ceruloplasmin (Cp) is the strongest ferroxidase in human plasma. Hereditary deficiency of this protein, named aceruloplasminemia, is an interesting model to elucidate the pathogenesis and pathophysiology of neurodegeneration induced by oxidative stress. Enhanced oxidative stress due to excessive iron accumulation is observed in the brains of aceruloplasminemia patients. Rotenone, a selective mitochondrial complex I inhibitor, induces neurodegeneration mimicking Parkinson's disease. We investigated the influence of Cp deficiency upon neurodegeneration using rotenone-treated, Cp-deficient mouse brains. Immunohistochemical examination showed that acrolein, one of the products of lipid peroxides, and ubiquitin were more markedly immunoreacted in the brains of rotenone-treated, Cp-deficient mice than in rotenone-untreated, Cp-deficient or rotenone-treated, wild-type mice. These molecules were localized in neuronal cells. These results suggested that rotenone-induced lipid peroxidation and accumulation of ubiquitin immunoreactivity were enhanced in the absence of Cp. Therefore, Cp may protect neuronal cells from oxidative stress-induced neurodegeneration.
Kaneko
Kazuma
K
Department of Neurology and Rheumatology, Shinshu University School of Medicine, 3-1-1 Asahi, 390-8621 Matsumoto, Japan. kazuma@shinshu-u.ac.jp
Hineno
Akiyo
A
Yoshida
Kunihiro
K
Ikeda
Shu-ichi
S
D000171:Acrolein / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002570:Ceruloplasmin / Q000172:deficiency* / Q000235:genetics; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012402:Rotenone; D025801:Ubiquitin / Q000378:metabolism
D025801:Ubiquitin; D012402:Rotenone; D000171:Acrolein; D002570:Ceruloplasmin