Overexpression of TFAM, NRF-1 and myr-AKT protects the MPP(+)-induced mitochondrial dysfunctions in neuronal cells
| Autor: | Youngmi Kim Pak, Hyo Geun Kim, Myung Sook Oh, Ying Piao |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
1-Methyl-4-phenylpyridinium Apoptosis Mitochondrion Biochemistry Rats Sprague-Dawley chemistry.chemical_compound Mice Neuroblastoma Phosphorylation Neurons Reverse Transcriptase Polymerase Chain Reaction MPTP Neurodegeneration Cell Differentiation Cell biology Mitochondria DNA-Binding Proteins Substantia Nigra Mitochondrial respiratory chain Female Signal Transduction Tyrosine 3-Monooxygenase Blotting Western Biophysics NF-E2-Related Factor 1 Biology Real-Time Polymerase Chain Reaction Mitochondrial Proteins Cell Line Tumor medicine Animals Humans RNA Messenger Molecular Biology Protein kinase B Cell Proliferation Herbicides TFAM medicine.disease Molecular biology Corpus Striatum Rats Mice Inbred C57BL Insulin receptor chemistry biology.protein Reactive Oxygen Species Proto-Oncogene Proteins c-akt Transcription Factors |
| Zdroj: | Biochimica et biophysica acta. 1820(5) |
| ISSN: | 0006-3002 |
| Popis: | Background Mitochondrial dysfunction is a prominent feature of neurodegenerative diseases including Parkinson's disease (PD), in which insulin signaling pathway may also be implicated because 50–80% of PD patients exhibited metabolic syndrome and insulin resistance. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its toxic metabolite, 1-methyl-4-phenyl-2,3-dihydropyridinium ion (MPP+), inhibit complex I in mitochondrial respiratory chain and are used widely to construct the PD models. But the precise molecular link between mitochondrial damage and insulin signaling remains unclear. Methods and results Using cell-based mitochondrial activity profiling system, we systemically demonstrated that MPP+ suppressed mitochondrial activity and mitochondrial gene expressions mediated by nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor A (TFAM) in SH-SY5Y cells. MPP+ fragmented mitochondrial networks and repressed phosphorylation of AKT. Similarly, the expressions of mitochondrial genes and tyrosine hydroxylase and AKT phosphorylation were reduced in substantia nigra and striatum of MPTP-injected mice. Transient transfection of TFAM, NRF-1, or myr-AKT reversed all aspects of the MPP+-mediated changes. Conclusions Mitochondrial activation by TFAM, NRF-1, and myr-AKT abrogated MPP+-mediated damages on mitochondria and insulin signaling, leading to recovery of nigrostriatal neurodegeneration. General significance We suggest that TFAM, NRF-1, and AKT may be the critical points of therapeutic intervention for PD. This article is part of a Special Issue entitled Biochemistry of Mitochondria. |
| Databáze: | OpenAIRE |
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