sgk1, a member of an RNA cluster associated with cell death in a model of Parkinson's disease
| Autor: | Barbara Siebertz, M. Foguet, Xin-Ran Zhu, Bodo Schoenebeck, Hermann Lübbert, Christine C. Stichel, Verian Bader |
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| Rok vydání: | 2005 |
| Předmět: |
Time Factors
Tyrosine 3-Monooxygenase Gene Expression In situ hybridization Biology Protein Serine-Threonine Kinases Immediate early protein Immediate-Early Proteins Antiparkinson Agents chemistry.chemical_compound Mice Parkinsonian Disorders Gene expression Glial Fibrillary Acidic Protein Selegiline medicine Animals Cluster Analysis Drug Interactions Northern blot RNA Messenger In Situ Hybridization Neurons Cell Death Water Deprivation Reverse Transcriptase Polymerase Chain Reaction General Neuroscience MPTP Gene Expression Profiling Neurodegeneration Age Factors Brain Nuclear Proteins medicine.disease Blotting Northern Molecular biology Gene expression profiling Blot Disease Models Animal chemistry Gene Expression Regulation Astrocytes Food Deprivation |
| Zdroj: | The European journal of neuroscience. 21(2) |
| ISSN: | 0953-816X |
| Popis: | In an effort to gain deeper insight into the molecular processes underlying neurodegeneration in Parkinson's disease, we performed gene expression profiling at several early time points after MPTP-injection into old (1-year) mice. We used a PCR-based gene expression profiling method, digital expression pattern display (DEPD), a method of very high sensitivity and reproducibility, which displays almost all transcripts of a tissue. To identify cell death-associated genes, we defined clusters of differentially expressed transcripts with expression behaviour that correlated with the temporal profile of cell death progression and characterized one of these cell death clusters further. We selected one of the strongest regulated genes, the serum and glucocorticoid-regulated kinase 1 (sgk1), and validated its differential expression by Northern blot analysis, semiquantitative PCR and in situ hybridization. Up-regulation of sgk1 (i) coincides with the onset of dopaminergic cell death in both the 8-week acute and 1-year subacute MPTP models, (ii) spans the entire brain, (iii) is attenuated by the l-deprenyl-mediated inhibition of the MPTP conversion to its active metabolite MPP+ and (iv) is not induced by dehydration. This study demonstrated that the combination of the DEPD technology, clustering analysis and a detailed histopathology is a useful tool for elucidating molecular pathways in neurodegenerative diseases. |
| Databáze: | OpenAIRE |
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