Wj. Parsons et al., DEVELOPMENTAL REGULATION OF CYTOCHROME-OXIDASE SUBUNIT VIA ISOFORMS IN CARDIAC AND SKELETAL-MUSCLE, American journal of physiology. Heart and circulatory physiology, 39(2), 1996, pp. 567-574
Physiological requirements for mitochondrial respiration change during
fetal and postnatal development of cardiac and skeletal muscle, parti
cularly after the abrupt transition from the hypoxic fetal environment
to the oxygen-rich milieu of the neonate. This study defines the patt
ern of expression of nuclear genes encoding the muscle-specific CH) an
d non-muscle-specific (L) isoforms of cytochrome oxidase (COX) subunit
VIa during pre- and postnatal development of striated muscles in the
mouse. In the early embyro, COX VIa-L was the predominant isoform expr
essed in all tissues. COX VIa-H mRNA was detectable as early as day 8
postcoitum (pc) in the heart, but not until gestational day 14 in skel
etal myofibers of the tongue, diaphragm, and other skeletal muscles. A
t late fetal stages up until birth (days 16-18 pc), COX VIa-L and COX
VIa-H were both expressed in striated myocytes, although the L form re
mained the dominant isoform. In postnatal animals, however, expression
of COX VIa-H increased whereas COX VIa-L decreased in a reciprocal ma
nner. Activation of the COX VIa-H gene also was observed during differ
entiation of murine myogenic cells in culture and was followed by dimi
nished expression of the COX VIa-L isoform in maturing myotubes, as in
the intact animal. We conclude that regulation of nuclear genes encod
ing subunits of COX is a component of the developmental programs that
govern cardiac and skeletal muscle differentiation and maturation in t
he mammalian fetus and neonate. COX VIa-L, the predominant isoform in
all fetal tissues, is gradually replaced by the muscle-specific H isof
orm in both cardiac and skeletal muscles, although this transition is
not complete until after birth.