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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yabuki, Yasushi Kobayashi, Yuka Shioda, Norifumi Owada, Yuji Onozato, Misaki Fukunaga, Kohji |
| Description | Author Affiliation: Shioda N ( From the Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 and.); Yabuki Y ( From the Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 and.); Kobayashi Y ( From the Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 and.); Onozato M ( From the Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 and.); Owada Y ( the Department of Organ Anatomy, Graduate School of Medicine, Yamaguchi University, Ube 755-8505, Japan.); Fukunaga K ( From the Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578 and kfukunaga@m.tohoku.ac.jp.) |
| Abstract | -Synuclein ( Syn) accumulation in dopaminergic (DA) neurons is partly regulated by long-chain polyunsaturated fatty acids. We found that fatty acid-binding protein 3 (FABP3, H-FABP), a factor critical for arachidonic acid (AA) transport and metabolism in brain, is highly expressed in DA neurons. Fabp3 knock-out (Fabp3(-/-)) mice were resistant to 1-methyl-1,2,3,6-tetrahydropiridine-induced DA neurodegeneration in the substantia nigra pars compacta and showed improved motor function. Interestingly, FABP3 interacted with Syn in the substantia nigra pars compacta, and Syn accumulation following 1-methyl-1,2,3,6-tetrahydropiridine treatment was attenuated in Fabp3(-/-) compared with wild-type mice. We confirmed that FABP3 overexpression aggravates AA-induced Syn oligomerization and promotes cell death in PC12 cells, whereas overexpression of a mutant form of FABP3 lacking fatty-acid binding capacity did not. Taken together, Syn oligomerization in DA neurons is likely aggravated by AA through FABP3 in Parkinson disease pathology. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 27 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-07-04 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Dopaminergic Neurons Drug Effects Fatty Acid-Binding Proteins Metabolism MPTP Poisoning Neurotoxins Toxicity Protein Multimerization Alpha-Synuclein Chemistry Animals Arachidonic Acid Pharmacology Cell Death Deficiency Gene Expression Regulation Kinetics Pathology Physiopathology Mice Motor Activity Neostriatum Cytology PC12 Cells Protein Binding Protein Structure, Quaternary Substantia Nigra Genetics Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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