Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases.

Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. Research Abstract Details 

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Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. Abstract Text:

Jennifer M Sacheck,Jon-Philippe K Hyatt,Anna Raffaello,R Thomas Jagoe,Roland R Roy,V Reggie Edgerton,Stewart H Lecker,Alfred L Goldberg,

We previously identified a common set of genes, termed atrogenes, whose expression is coordinately induced or suppressed in muscle during systemic wasting states (fasting, cancer cachexia, renal failure, diabetes). To determine whether this transcriptional program also functions during atrophy resulting from loss of contractile activity and whether atrogene expression correlates with the rate of muscle weight loss, we used cDNA microarrays and RT-polymerase chain reaction to analyze changes in mRNA from rat gastrocnemius during disuse atrophy induced by denervation or spinal cord isolation. Three days after Den or SI, the rate of muscle weight loss was greatest, and 78% of the atrogenes identified during systemic catabolic states were induced or repressed. Of particular interest were the large inductions of key ubiquitin ligases, atrogin-1 (35- to 44-fold) and MuRF1 (12- to 22-fold), and the suppression of PGC-1alpha and PGC-1beta coactivators (15-fold). When atrophy slowed (day 14), the expression of 92% of these atrogenes returned toward basal levels. At 28 days, the atrophy-inducing transcription factor, FoxO1, was still induced and may be important in maintaining the "atrophied" state. Thus, 1) the atrophy associated with systemic catabolic states and following disuse involves similar transcriptional adaptations; and 2) disuse atrophy proceeds through multiple phases corresponding to rapidly atrophying and atrophied muscles that involve distinct transcriptional patterns.

Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. Publishing Authors By Initials

JM Sacheck,JP Hyatt,A Raffaello,RT Jagoe,RR Roy,VR Edgerton,SH Lecker,AL Goldberg,

For similar genetic processes: gene expression: transcription, genetic research abstracts see: genetic processes: gene expression: transcription, genetic research

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Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The FASEB journal : official publication of the Fe

VOLUME: 21

Page Numbers: 140-55

Journal Abbreviation: FASEB J.

ISSN: 1530-6860

DAY: 20

MONTH: 11

YEAR: 2006

Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. Information

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LANGUAGE: eng

NlmUniqueID: 8804484

Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases. Keywords Mesh Terms:

KEYWORDS: Transcription, Genetic

MESH TERMS: pathology

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Grant and Affiliation Information for Rapid disuse and denervation atrophy involve transcriptional changes similar to those of muscle wasting during systemic diseases.

AFFILIATION: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS16333

ACRONYM: NS

MEDLINETA: FASEB J

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