2010 Fiscal Year Final Research Report
Regulation of neuronal cell function organized by deubiquitinating enzymes
Project/Area Number |
19200032
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Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurochemistry/Neuropharmacology
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Research Institution | National Center of Neurology and Psychiatry |
Principal Investigator |
WADA Keiji National Center of Neurology and Psychiatry, 神経研究所疾病研究第4部, 部長 (70250222)
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Project Period (FY) |
2007 – 2010
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Research Abstract |
In this study, we analyzed the effect of genetic (I93M mutation) and environmental modification (oxidative stress) of a deubiquitinating enzyme, UCH-L1. In the brain, UCH-L1 shows neuron-specific expression and is believed to be involved in the pathogenesis of Parkinson's disease. We found that oxidized UCH-L1 showed its increased insolubility, and the formation of aggregation. These features were also observed in I93M IUCH-L1. Both oxidized UCH-L1 and I93M UCH-L1 showed the increased interaction with other proteins, and some of the proteins were overlapped. These findings suggest that oxidized UCH-L1 and I93M UCH-L1 share some molecular features. We next observed that gad mice, which lack the expression of UCH-L1, showed the deterioration of motor discoordination when they were fed with vitamin E-deficient diet. Wild type mice did not show any changes in motor function when they were fed with the diet. These observations suggest that UCH-L1 may play a protective role against oxidative stress in vivo, because vitamin E deficiency is know to cause the increase of oxidative stress in vivo. Then, we analyzed UCH-L3 null mutant. UCH-L3 is a homologue of UCH-L1 and shows ubiquitous expression in vivo. We observed that, in the mutant, lipid metabolism was altered in the muscle and adipose tissue. We also detected that monoubiquitin and di-ubiquitin are endogenous regulator of the enzyme activities of UCH-L1 and UCH-L3. These results suggests that the two enzymes co-operatively work in vivo.
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Research Products
(38 results)
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[Journal Article] Effects of UCH-L1 on alpha-synuclein over-expression mouse model of Parkinson's disease.2009
Author(s)
Yasuda T., Nihira T., Ren Y. R., Cao X.Q., Wada K., Setsuie R., Kabuta T., Wada K., Hattori N., Mizuno Y., Mochizuki H.
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Journal Title
J Neurochem. 108
Pages: 932-944
Peer Reviewed
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[Journal Article] Ubiquitin C-terminal hydrolase-L3 knockout mice are resistant to diet-induced obesity and show increased activation of AMP-activated protein kinase in skeletal muscle.2009
Author(s)
Setsuie R., Suzuki M., Kabuta T., Fujita H., Miura S., Ichihara N., Yamada D., Wang Y.L., Ezaki O., Suzuki Y., Wada K.
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Journal Title
FASEB J 23
Pages: 4148-4157
Peer Reviewed
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