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Published on: April 29, 2011
Control of myogenic factor genes by the membrane depolarization/protein kinase C cascade in chick skeletal muscle
C F Huang1, C M Neville, J Schmidt
1Department of Biochemistry and Cell Biology, State University of New York, Stony Brook 11794.
Abstract:
Myogenic factor genes were found to respond differentially to electrical stimulation of denervated chick skeletal muscle. Myogenin gene activity declined rapidly (t1/2: approximately 2 min), comparable to the rate of acetylcholine receptor (AChR) gene inactivation, while other myogenic bHLH genes either lost activity more slowly (MyoD) or not at all (myf5, herculin). Protein kinase C (PKC) is known to couple membrane activity to AChR gene inactivation; myogenin gene transcription was also rapidly blocked by the PKC activator PMA, whereas electrostimulation remained without effect on myogenin gene activity in muscle that was either exposed to the kinase inhibitor staurosporine or chronically treated with PMA to deplete PKC. These results attest to a special role for myogenin in the activation of AChR genes in denervation supersensitivity.
Insights
Electrical stimulation differentially affects myogenic factor genes in chick skeletal muscle. Myogenin gene activity rapidly declines, suggesting a key role in acetylcholine receptor gene activation during denervation.
Area of Science:
- Muscle physiology
- Molecular biology
- Neuroscience
Background:
- Denervation of skeletal muscle leads to significant changes in gene expression.
- Acetylcholine receptor (AChR) gene expression is rapidly downregulated following denervation.
- Myogenic factor genes play crucial roles in muscle development and maintenance.
Purpose of the Study:
- To investigate the differential response of myogenic factor genes to electrical stimulation in denervated chick skeletal muscle.
- To elucidate the role of myogenin in the regulation of AChR gene activity during denervation supersensitivity.
- To examine the involvement of Protein Kinase C (PKC) signaling in these processes.
Main Methods:
- Electrical stimulation of denervated chick skeletal muscle.
- Quantitative analysis of myogenic factor gene activity (myogenin, MyoD, myf5, herculin).
- Pharmacological manipulation using PKC activator (PMA) and kinase inhibitor (staurosporine).
Main Results:
- Myogenin gene activity declined rapidly (t1/2 ≈ 2 min) post-denervation, mirroring AChR gene inactivation.
- Other myogenic bHLH genes (MyoD, myf5, herculin) showed slower or no decline in activity.
- PKC activation rapidly blocked myogenin transcription; electrical stimulation's effect was abolished by PKC inhibition or depletion.
Conclusions:
- Myogenin exhibits a unique, rapid response to denervation, distinct from other myogenic factors.
- Myogenin plays a specialized role in activating AChR genes during denervation supersensitivity.
- PKC signaling is critical for the rapid inactivation of myogenin gene transcription following denervation.
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