期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 12, 页码 4721-4726出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0800979105
关键词
colchicine; high throughput
资金
- NHLBI NIH HHS [K08 HL079172, HL079172] Funding Source: Medline
- NIDDK NIH HHS [R56 DK054477, R01 DK061562, DK54477, R01 DK054477, DK61562, R24 DK080261] Funding Source: Medline
- NINDS NIH HHS [R21 NS059440, NS059440] Funding Source: Medline
The transcriptional coactivator PGC-1 alpha is a potent regulator of several metabolic pathways, including, in particular, the activation of oxidative phosphorylation and mitochondrial biogenesis. Recent evidence suggests that increasing PGC-1 alpha activity may have beneficial effects in various conditions, including muscular dystrophy, diabetes, and neurodegenerative diseases. We describe here a high-throughput screen to identify small molecules that induce PGC-1 alpha expression in skeletal muscle cells. A number of drug classes are identified, including glucocorticoids, microtubule inhibitors, and protein synthesis inhibitors. These drugs induce PGC-1 alpha mRNA, and the expression of a number of genes known to be regulated by PGC-1 alpha. No induction of these target genes is seen in PGC-1 alpha -/- cells, demonstrating that the drugs act through PGC-1 alpha. These data demonstrate the feasibility of high-throughput screening for inducers of PGC-1 alpha. Moreover, the data identify microtubule inhibitors and protein synthesis inhibitors as modulators of PGC-1 alpha and oxidative phosphorylation.
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