Parsons W J, Williams R S, Shelton J M, Luo Y, Kessler D J, Richardson J A
Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas 75235, USA.
Am J Physiol. 1996 Feb;270(2 Pt 2):H567-74. doi: 10.1152/ajpheart.1996.270.2.H567.
Physiological requirements for mitochondrial respiration change during fetal and postnatal development of cardiac and skeletal muscle, particularly after 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 postnatal development of striated muscles in the mouse. In the early embryo, COX VIa-L was the predominant isoform expressed 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 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, although the L form remained the dominant isoform. In postnatal animals, however, expression of COX VIa-H increased whereas COX VIa-L decreased in a reciprocal manner. Activation of the COX VIa-H gene also was observed during differentiation of nurine 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 COX 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, although this transition is not complete until after birth.
在心脏和骨骼肌的胎儿期及出生后发育过程中，尤其是从缺氧的胎儿环境突然过渡到富含氧气的新生儿环境后，线粒体呼吸的生理需求会发生变化。本研究确定了在小鼠横纹肌出生前和出生后发育过程中，编码细胞色素氧化酶（COX）亚基VIa的肌肉特异性（H）和非肌肉特异性（L）同工型的核基因的表达模式。在早期胚胎中，COX VIa-L是所有组织中表达的主要同工型。早在受孕后第8天（pc），心脏中就可检测到COX VIa-H mRNA，但直到妊娠第14天，舌、膈肌和其他骨骼肌的肌纤维中才检测到。在胎儿后期直至出生（妊娠第16 - 18天），COX VIa-L和COX VIa-H在横纹肌细胞中均有表达，尽管L型仍然是主要同工型。然而，在出生后的动物中，COX VIa-H的表达增加，而COX VIa-L的表达则以相反的方式减少。在培养的小鼠成肌细胞分化过程中也观察到COX VIa-H基因的激活，随后在成熟的肌管中COX VIa-L同工型的表达减少，与完整动物中的情况一样。我们得出结论，编码COX亚基的核基因的调控是控制哺乳动物胎儿和新生儿心脏和骨骼肌分化及成熟的发育程序的一个组成部分。COX VIa-L是所有胎儿组织中的主要同工型，在心脏和骨骼肌中逐渐被肌肉特异性的H同工型所取代，尽管这种转变直到出生后才完成。
