A role for voltage-dependent anion channel Vdac1 in polyglutamine-mediated neuronal cell death.
Expansion of trinucleotide repeats in coding and non-coding regions of genes is associated with sixteen neurodegenerative disorders. However, the molecular effects that lead to neurodegeneration have remained elusive. We have explored the role of transcriptional dysregulation by TATA-box binding pro...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2007-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2064964?pdf=render |
| _version_ | 1828414137840959488 |
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| author | Tanay Ghosh Neeraj Pandey Arindam Maitra Samir K Brahmachari Beena Pillai |
| author_facet | Tanay Ghosh Neeraj Pandey Arindam Maitra Samir K Brahmachari Beena Pillai |
| author_sort | Tanay Ghosh |
| collection | DOAJ |
| description | Expansion of trinucleotide repeats in coding and non-coding regions of genes is associated with sixteen neurodegenerative disorders. However, the molecular effects that lead to neurodegeneration have remained elusive. We have explored the role of transcriptional dysregulation by TATA-box binding protein (TBP) containing an expanded polyglutamine stretch in a mouse neuronal cell culture based model. We find that mouse neuronal cells expressing a variant of human TBP harboring an abnormally expanded polyQ tract not only form intranuclear aggregates, but also show transcription dysregulation of the voltage dependent anion channel, Vdac1, increased cytochrome c release from the mitochondria and upregulation of genes involved in localized neuronal translation. On the other hand, unfolded protein response seemed to be unaffected. Consistent with an increased transcriptional effect, we observe an elevated promoter occupancy by TBP in vivo in TATA containing and TATA-less promoters of differentially expressed genes. Our study suggests a link between transcriptional dysfunction and cell death in trinucleotide repeat mediated neuronal dysfunction through voltage dependent anion channel, Vdac1, which has been recently recognized as a critical determinant of cell death. |
| first_indexed | 2024-12-10T13:21:52Z |
| format | Article |
| id | doaj.art-6fb53803ca864467b7f24cfe9392629a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T13:21:52Z |
| publishDate | 2007-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-6fb53803ca864467b7f24cfe9392629a2022-12-22T01:47:18ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-01-01211e117010.1371/journal.pone.0001170A role for voltage-dependent anion channel Vdac1 in polyglutamine-mediated neuronal cell death.Tanay GhoshNeeraj PandeyArindam MaitraSamir K BrahmachariBeena PillaiExpansion of trinucleotide repeats in coding and non-coding regions of genes is associated with sixteen neurodegenerative disorders. However, the molecular effects that lead to neurodegeneration have remained elusive. We have explored the role of transcriptional dysregulation by TATA-box binding protein (TBP) containing an expanded polyglutamine stretch in a mouse neuronal cell culture based model. We find that mouse neuronal cells expressing a variant of human TBP harboring an abnormally expanded polyQ tract not only form intranuclear aggregates, but also show transcription dysregulation of the voltage dependent anion channel, Vdac1, increased cytochrome c release from the mitochondria and upregulation of genes involved in localized neuronal translation. On the other hand, unfolded protein response seemed to be unaffected. Consistent with an increased transcriptional effect, we observe an elevated promoter occupancy by TBP in vivo in TATA containing and TATA-less promoters of differentially expressed genes. Our study suggests a link between transcriptional dysfunction and cell death in trinucleotide repeat mediated neuronal dysfunction through voltage dependent anion channel, Vdac1, which has been recently recognized as a critical determinant of cell death.http://europepmc.org/articles/PMC2064964?pdf=render |
| spellingShingle | Tanay Ghosh Neeraj Pandey Arindam Maitra Samir K Brahmachari Beena Pillai A role for voltage-dependent anion channel Vdac1 in polyglutamine-mediated neuronal cell death. PLoS ONE |
| title | A role for voltage-dependent anion channel Vdac1 in polyglutamine-mediated neuronal cell death. |
| title_full | A role for voltage-dependent anion channel Vdac1 in polyglutamine-mediated neuronal cell death. |
| title_fullStr | A role for voltage-dependent anion channel Vdac1 in polyglutamine-mediated neuronal cell death. |
| title_full_unstemmed | A role for voltage-dependent anion channel Vdac1 in polyglutamine-mediated neuronal cell death. |
| title_short | A role for voltage-dependent anion channel Vdac1 in polyglutamine-mediated neuronal cell death. |
| title_sort | role for voltage dependent anion channel vdac1 in polyglutamine mediated neuronal cell death |
| url | http://europepmc.org/articles/PMC2064964?pdf=render |
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