Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1{alpha} and oxidative phosphorylation.

Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1{alpha} and oxidative phosphorylation. Research Abstract Details 

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Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1{alpha} and oxidative phosphorylation. Abstract Text:

Zoltan Arany,Bridget K Wagner,Yanhong Ma,Jessica Chinsomboon,Dina Laznik,Bruce M Spiegelman,Zoltan Arany,Bridget K Wagner,Yanhong Ma,Jessica Chinsomboon,Dina Laznik,Bruce M Spiegelman,

The transcriptional coactivator PGC-1alpha 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-1alpha 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-1alpha expression in skeletal muscle cells. A number of drug classes are identified, including glucocorticoids, microtubule inhibitors, and protein synthesis inhibitors. These drugs induce PGC-1alpha mRNA, and the expression of a number of genes known to be regulated by PGC-1alpha. No induction of these target genes is seen in PGC-1alpha -/- cells, demonstrating that the drugs act through PGC-1alpha. These data demonstrate the feasibility of high-throughput screening for inducers of PGC-1alpha. Moreover, the data identify microtubule inhibitors and protein synthesis inhibitors as modulators of PGC-1alpha and oxidative phosphorylation.

Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1{alpha} and oxidative phosphorylation. Publishing Authors By Initials

Z Arany,BK Wagner,Y Ma,J Chinsomboon,D Laznik,BM Spiegelman,Z Arany,BK Wagner,Y Ma,J Chinsomboon,D Laznik,BM Spiegelman,

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Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1{alpha} and oxidative phosphorylation. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 105

Page Numbers: 4721-6

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 1091-6490

DAY: 17

MONTH: 03

YEAR: 2008

Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1{alpha} and oxidative phosphorylation. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

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Grant and Affiliation Information for Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1{alpha} and oxidative phosphorylation.

AFFILIATION: Dana Farber Cancer Institute and the Department of Cell Biology, Harvard Medical School, Boston, MA 02115.

Country: United States

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MEDLINETA: Proc Natl Acad Sci U S A

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