PPARγ coactivator-1α expression during thyroid hormone- and contractile activity-induced mitochondrial adaptations
Bibliographic record
Abstract
The transcriptional coactivator the peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) has been identified as an important mediator of mitochondrial biogenesis based on its ability to interact with transcription factors that activate nuclear genes encoding mitochondrial proteins. The induction of PGC-1alpha protein expression under conditions that provoke mitochondrial biogenesis, such as contractile activity or thyroid hormone (T(3)) treatment, is not fully characterized. Thus we related PGC-1alpha protein expression to cytochrome c oxidase (COX) activity in 1) tissues of varying oxidative capacities, 2) tissues from animals treated with T(3), and 3) skeletal muscle subject to contractile activity both in cell culture and in vivo. Our results demonstrate a strong positive correlation (r = 0.74; P < 0.05) between changes in PGC-1alpha and COX activity, used as an index of mitochondrial adaptations. The highest constitutive levels of PGC-1alpha were found in the heart, whereas the lowest were measured in fast-twitch white muscle and liver. T(3) increased PGC-1alpha content similarly in both fast- and slow-twitch muscle, as well as in the liver, but not in heart. T(3) also induced early (6 h) increases in AMP-activated protein kinase (AMPKalpha) activity, as well as later (5 day) increases in p38 MAP kinase activity in slow-twitch, but not in fast-twitch, muscle. Contractile activity provoked early increases in PGC-1alpha, coincident with increases in mitochondrial transcription factor A (Tfam), and nuclear respiratory factor-1 (NRF-1) protein expression, suggesting that PGC-1alpha is physiologically important in coordinating the expression of the nuclear and mitochondrial genomes. Ca(2+) ionophore treatment of muscle cells led to an approximately threefold increase in PGC-1alpha protein, and contractile activity induced rapid and marked increases in both p38 MAP kinase and AMPKalpha activities. 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) treatment of muscle cells also led to parallel increases in AMPKalpha activity and PGC-1alpha protein levels. These data are consistent with observations that indicate that increases in PGC-1alpha protein are affected by Ca(2+) signaling mechanisms, AMPKalpha activity, as well as posttranslational phosphorylation events that increase PGC-1alpha protein stability. Our data support a role for PGC-1alpha in the physiological regulation of mitochondrial content in a variety of tissues and suggest that increases in PGC-1alpha expression form part of a unifying pathway that promotes both T(3)- and contractile activity-induced mitochondrial adaptations.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".