Gene expression profiles and protein balance in skeletal muscle of burned children after β-adrenergic blockade

David Herndon, Mohan R K Dasu, Robert R. Wolfe, Robert E. Barrow

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Propranolol, a nonselective β-blocker, has been shown effective in hypermetabolic burn patients by decreasing cardiac work, protein catabolism, and lipolysis. This study investigates the effect of propranolol on gene and protein expression changes in skeletal muscle of burned children by use of high-density oligonucleotide arrays to establish the genetic profiles and stable isotope technique to quantitate protein synthesis. Thirty-seven children (mean age 9.7 ± 1.1 yr) were randomized into groups to receive placebo (n = 23) or propranolol (n = 14) titrated to reduce heart rate by 15%. Children had >40% total body surface area burns (mean 43 ± 5.6%). Protein net balance was determined by stable-isotope infusion technique. Total RNA from muscle biopsies was isolated, labeled, and cRNA hybridized to the HG-U95Av2 Affymetrix array. Mean net balance of protein synthesis and breakdown was -14.3 ± 12.9 nmol·min-1·100 ml leg volume -1 for placebo and +69.3 ± 34.9 nmol·min -1·100 ml leg volume-1 in the propranolol-treated children (P - 0.012). Comparison of 12,000 genes in burned children receiving placebo showed increased expression of two genes with time, whereas children receiving propranolol showed increased expression of nine genes with a decrease in five genes. We conclude that burned children receiving propranolol showed a significant upregulation in genes involved in muscle metabolism and downregulation of an important enzyme involved in gluconeogenesis and insulin resistance compared with burned children receiving placebo. The upregulation of genes involved in muscle metabolism correlates well with the increase in net protein balance across the leg.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume285
Issue number4 48-4
StatePublished - Oct 1 2003

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Transcriptome
Gene expression
Propranolol
Adrenergic Agents
Muscle
Skeletal Muscle
Genes
Proteins
Placebos
Metabolism
Isotopes
Leg
Gene Expression
Muscles
Complementary RNA
Up-Regulation
Biopsy
Oligonucleotides
Gluconeogenesis
Lipolysis

Keywords

  • Hypermetabolism
  • Microarray analysis
  • Muscle catabolism
  • Propranolol

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

Gene expression profiles and protein balance in skeletal muscle of burned children after β-adrenergic blockade. / Herndon, David; Dasu, Mohan R K; Wolfe, Robert R.; Barrow, Robert E.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 285, No. 4 48-4, 01.10.2003.

Research output: Contribution to journalArticle

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