Developmental regulation of cytochrome oxidase subunit via isoforms in cardiac and skeletal muscle. Parsons, William J., R. Sanders Williams, John M. Shelton, Yuxia Luo, David J. Kessler, James A. Richardson. Departments of Internal Medicine, Biochemistry, and Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235, and Medical Service, Veterans Affairs Medical Center, Dallas, Texas 75216
APStracts 2:0497H, 1995.
Physiological requirements for mitochondrial respiration change during fetal and postnatal development of cardiac and skeletal muscle, particularly following the abrupt transition from the hypoxic fetal environment to the oxygen-rich milieu of the neonate. This study defines the pattern of expression of nuclear genes encoding the muscle-specific (H) and non-muscle-specific (L) isoforms of cytochrome oxidase (COX) subunit VIa during pre- and post-natal development of striated muscles in the mouse. In the early embyro, COX VIa-L was the predominant isoform expressed in all tissues. COX VIa-H mRNA was detectable as early as Day 8 post-coitum (pc) in the heart, but not until gestational Day 14 in skeletal myofibers of the tongue, diaphragm, and other skeletal muscles. At late fetal stages up until birth (Days 16-18 pc), COX VIa-L and COX VIa-H were both expressed in striated myocytes, though the L form remained the dominant isoform. In post-natal animals, however, expression of COX VIa-H increased while COX VIa-L decreased in a reciprocal manner. Activation of the COX VIa-H gene also was observed during differentiation of murine myogenic cells in culture, and was followed by diminished expression of the COX VIa-L isoform in maturing myotubes, as in the intact animal. We conclude that regulation of nuclear genes encoding subunits of cytochrome oxidase is a component of the developmental programs that govern cardiac and skeletal muscle differentiation and maturation in the mammalian fetus and neonate. COX VIa-L, the predominant isoform in all fetal tissues, is gradually replaced by the muscle-specific H isoform in both cardiac and skeletal muscles, though this transition is not complete until after birth. 

Received 19 December 1994; accepted in final form 17 July 1995.
APS Manuscript Number H1108-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95