Exp Mol Med.  2003 Feb;35(1):23-29.

Acetyl-CoA carboxylase beta expression mediated by MyoD and muscle regulatory factor 4 is differentially affected by retinoic acid receptor and retinoid X receptor

• Kim JY
• Lee JJ
• Kim KS

Abstract

Mammals have two major isoforms of acetyl-CoA carboxyase (ACC). The 275 kDa beta-form (ACC beta) is predominantly in heart and skeletal muscle while the 265 kDa alpha-form (ACC alpha) is the major isoform in lipogenic tissues such as liver and adipose tissue. ACC alpha is thought to control fatty acid oxidation by means of the ability of malonyl-CoA to inhibit carnitine palmitoyl-CoA transferase-1 (CPT-1), which is a rate-limiting enzyme of fatty acid oxidation in mitochondria. Previously, it was reported that MyoD and other muscle regulating factors (MRFs) up-regulate the expression of ACC beta by interactions between these factors and several cis-elements of ACC beta promoter. We described here that ACC beta expression mediated by MRFs is regulated by retinoic acids. Endogenous expression of ACCb in differentiated H9C2 myotube was significantly increased by retinoic acid treatment. However, on transient transfection assay in H9C2 myoblast, ACC beta promoter activity was suppressed by RXRa and more severely by RAR alpha. These effects on ACCb expression in myoblasts and myotubes by RXR alpha and RAR alpha seem to be mediated by their interactions with MRFs because no consensus sequence for RXR alpha and RAR alpha has been found in ACC beta promoter and retinoic acid receptors did not affect this promoter activities by itself. In transient transfection in NIH3T3 fibroblast, the activation of ACC beta promoter by MyoD, main MRF in myoblast, was significantly suppressed by RAR alpha and to a less extent by RXR alpha while the RXR alpha drastically augmented the activation by MRF4, major MRF in myotube. These results explained that retinoic acids differentially affected the action of MRFs according to their types and RXR alpha specially elevates the expression of muscle specific genes by stimulating the action of MRF4.

Keyword

acetyl-CoA carboxylase; muscles; MyoD protein; receptors; retinoic acid; retinoids; transcription factors

MeSH Terms

3T3 Cells
Acetyl-CoA Carboxylase/genetics/*metabolism
Animals
Cell Differentiation
Cells, Cultured
Gene Expression Regulation, Enzymologic/drug effects
Mice
MyoD Protein/*metabolism
Myoblasts/drug effects/metabolism
Myogenic Regulatory Factors/*metabolism
Promoter Regions (Genetics)/drug effects
Receptors, Retinoic Acid/genetics/*metabolism
Trans-Activation (Genetics)
Transcription Factors/genetics/*metabolism
Tretinoin/pharmacology