Regulation of Gene Expression by Ractopamine in Porcine Skeletal Muscle
Author | : David Lee Morris |
Publisher | : |
Total Pages | : 180 |
Release | : 2003 |
ISBN-10 | : OCLC:53316105 |
ISBN-13 | : |
Rating | : 4/5 (05 Downloads) |
Book excerpt: The [beta]-adrenergic agonist, ractopamine, stimulates muscle hypertrophy and increases lean body composition in the pig. Increases in protein synthetic rate, changes in muscle fiber type, and increases in the pre-translational expression of skeletal muscle-specific genes in skeletal muscle have been documented after treatment with ractopamine. These effects may be the accumulation of changes in enzymatic activity, substrate utilization, and/or gene transcription. This research addressed ractopamine's capacity to alter gene expression. In the first study, the transcriptional responsiveness of the porcine skeletal [alpha]-actin promoter was evaluated. In porcine myotubes, ractopamine stimulated the accumulation of skeletal [alpha]-actin mRNA. However, the previously cloned full-length porcine skeletal [alpha]-actin promoter was unresponsive to ractopamine treatment. It is possible that a novel mechanism regulates the accumulation of skeletal [alpha]-actin mRNA, possibly via an unidentified regulatory element within, or adjacent to, the gene's locus. Alternatively, skeletal [alpha]-actin mRNA stability could be enhanced in response to ractopamine. In the second study, the suppression subtractive hybridization technique was used to identify differentially expressed genes in porcine skeletal muscle after feeding ractopamine to pigs for three days. From this initial screen, nine genes and one expressed sequence tag were tentatively identified. Further analysis confirmed that ractopamine increased the steady state mRNA abundance of calmodulin-1 by approximately two-fold. This is the first study to implicate calcium-modulated proteins and calcium signaling as potentially being involved in the cellular response to ractopamine in porcine skeletal muscle. Future investigations should address the physiological significance of increased calmodulin expression, as calcium/calmodulin dependent proteins have been implicated in both muscle hypertrophy and muscle fiber type transition.