Comparison of gene expression of 2-mo denervated, 2-mo stimulated- denervated, and control rat skeletal muscles

Tatiana Kostrominova, Douglas E. Dow, Robert G. Dennis, Richard A. Miller, John A. Faulkner

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Loss of innervation in skeletal muscles leads to degeneration, atrophy, and loss of force. These dramatic changes are reflected in modifications of the mRNA expression of a large number of genes. Our goal was to clarify the broad spectrum of molecular events associated with long-term denervation of skeletal muscles. A microarray study compared gene expression profiles of 2-mo denervated and control extensor digitorum longus (EDL) muscles from 6-mo-old rats. The study identified 121 genes with increased and 7 genes with decreased mRNA expression. The expression of 107 of these genes had not been identified previously as changed after denervation. Many of the genes identified were genes that are highly expressed in skeletal muscles during embryonic development, downregulated in adults, and upregulated after denervation of muscle fibers. Electrical stimulation of denervated muscles preserved muscle mass and maximal force at levels similar to those in the control muscles. To understand the processes underlying the effect of electrical stimulation on denervated skeletal muscles, mRNA and protein expression of a number of genes, identified by the microarray study, was compared. The hypothesis was that loss of nerve action potentials and muscle contractions after denervation play the major roles in upregulation of gene expression in skeletal muscles. With electrical stimulation of denervated muscles, the expression levels for these genes were significantly downregulated, consistent with the hypothesis that loss of action potentials and/or contractions contribute to the alterations in gene expression in denervated skeletal muscles.

Original languageEnglish (US)
Pages (from-to)227-243
Number of pages17
JournalPhysiological Genomics
Volume22
DOIs
StatePublished - Oct 2005
Externally publishedYes

Fingerprint

Skeletal Muscle
Gene Expression
Denervation
Muscles
Electric Stimulation
Genes
Messenger RNA
Action Potentials
Down-Regulation
Muscle Denervation
Muscle Proteins
Muscle Contraction
Transcriptome
Atrophy
Embryonic Development
Up-Regulation

Keywords

  • Electrical stimulation
  • Gene array
  • Long-term denervation
  • Muscle atrophy

ASJC Scopus subject areas

  • Physiology
  • Genetics

Cite this

Comparison of gene expression of 2-mo denervated, 2-mo stimulated- denervated, and control rat skeletal muscles. / Kostrominova, Tatiana; Dow, Douglas E.; Dennis, Robert G.; Miller, Richard A.; Faulkner, John A.

In: Physiological Genomics, Vol. 22, 10.2005, p. 227-243.

Research output: Contribution to journalArticle

Kostrominova, Tatiana ; Dow, Douglas E. ; Dennis, Robert G. ; Miller, Richard A. ; Faulkner, John A. / Comparison of gene expression of 2-mo denervated, 2-mo stimulated- denervated, and control rat skeletal muscles. In: Physiological Genomics. 2005 ; Vol. 22. pp. 227-243.
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