title: Microarray expression profiling in 6-hydroxydopamine-induced dopaminergic neuronal cell death.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disorder and is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta. To discover potential key molecules in this process, we utilized cDNA microarray technology to obtain an expression profile of transcripts in MN9D dopaminergic neuronal cells treated with 6-hydroxydopamine. Using a self-organizing map algorithm, data mining and clustering were combined to identify distinct functional subgroups of genes. We identified alterations in the expression of 81 genes in eight clusters. Among these genes, we verified protein expression patterns of MAP kinase phosphatase 1 and sequestosome 1 using both cell culture and rat brain models of PD. Immunological analyses revealed increased expression levels as well as aggregated distribution patterns of these gene products in 6-hydroxydopamine-treated dopaminergic neurons. In addition to the identification of other proteins that are known to be associated with protein aggregation, our results raise the possibility that a more widespread set of proteins may be associated with the generation of protein aggregates in dying neurons. Further research to determine the functional roles of other altered gene products within the same cluster as well as the seven remaining clusters may provide new insights into the neurodegeneration that underlies PD pathogenesis.
authors: Department of Biology, Yonsei University College of Life Science and Biotechnology, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul, Korea.
authors: Bokyung
authors: B
authors: Park
authors: Chang-Ki
authors: CK
authors: Oh
authors: Won-Seok
authors: WS
authors: Choi
authors: In Kwon
authors: IK
authors: Chung
authors: Moussa B H
authors: MB
authors: Youdim
authors: Young J
authors: YJ
authors: Oh
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016627:Oxidopamine / Q000633:toxicity*; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000473:pathology
chemical_list: D016627:Oxidopamine