Abstract |
Peroxisome proliferator-activated receptor-gamma (PPARγ) coactivator-1 alpha (PGC-1α) is involved in the regulation of mitochondrial biogenesis, respiration, and adaptive thermogenesis. The full-length PGC-1α (FL-PGC-1α) comprises multiple functional domains interacting with several transcriptional regulatory factors such as nuclear respiratory factors, estrogen-related receptors, and PPARs; however, a number of PGC-1α splice variants have also been reported recently. In this study, we examined the expression levels of FL-PGC-1α and N-truncated PGC-1α (NT-PGC-1α), a shorter but functionally active splice variant of PGC-1α protein, in N171-82Q transgenic and 3-nitropropionic acid-induced murine model of Huntington's disease (HD). The expression levels were determined by RT-PCR in three brain areas (striatum, cortex, and cerebellum) in three age groups (8, 12, and 16 weeks). Besides recapitulating prior findings that NT-PGC-1α is preferentially increased in 16 weeks of age in transgenic HD animals, we detected age-dependent alterations in both models, including a cerebellum-predominant upregulation of both PGC-1α variants in transgenic mice, and a striatum-predominant upregulation of both PGC-1α variants after acute 3-nitropropionic acid intoxication. The possible relevance of this expression pattern is discussed. Based on our results, we assume that increased expression of PGC-1α may serve as a compensatory mechanism in response to mitochondrial damage in transgenic and toxin models of HD, which may be of therapeutic relevance.
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Authors | Rita Török, Júlia Anna Kónya, Dénes Zádori, Gábor Veres, Levente Szalárdy, László Vécsei, Péter Klivényi |
Journal | Cellular and molecular neurobiology
(Cell Mol Neurobiol)
Vol. 35
Issue 2
Pg. 293-301
(Mar 2015)
ISSN: 1573-6830 [Electronic] United States |
PMID | 25319408
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Nitro Compounds
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
- Ppargc1a protein, mouse
- Propionates
- RNA, Messenger
- Transcription Factors
- 3-nitropropionic acid
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Topics |
- Animals
- Disease Models, Animal
- Female
- Gene Expression Regulation
- Huntington Disease
(genetics, pathology)
- Male
- Mice, Inbred C57BL
- Mice, Transgenic
- Nitro Compounds
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
- Propionates
- RNA, Messenger
(genetics, metabolism)
- Transcription Factors
(genetics, metabolism)
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