Cardiac cytochrome-c oxidase deficiency occurs during late postnatal development in progeny of copper-deficient rats.
Although cytochrome-c oxidase (CCO) is a copper-dependent enzyme, the effect of maternal copper deficiency on the expression of CCO activity during postnatal development of the neonatal rat heart has not been investigated extensively. Here, we show that CCO activity in heart mitochondria isolated from neonates of copper-deficient dams did not exhibit significant reductions until postnatal days (PND) 15 and 21. In addition, immunoblot analysis indicated that the CCO subunit (Cox-1) was reduced on postnatal Days 10 and 21, and that Cox-4 was reduced on PND 21 in heart mitochondria of the neonates from copper-deficient dams. These findings indicate that the impairment of CCO activity in neonatal heart by maternal copper deficiency occurs late in the postnatal heart development. Furthermore, the concurrent reductions in Cox-1 and Cox-4 suggest that the impaired CCO activity reflects a CCO deficiency in heart mitochondria. CCO activity and Cox-1 in heart mitochondria were not fully restored by 6 weeks of postweaning copper repletion in the pups of copper-deficient dams. This indicates that prolonged maternal intake of moderately low dietary copper produces CCO deficiency in cardiac mitochondria of neonates during late postnatal heart development, after terminal differentiation of cardiomyocytes occurs. The resistance of CCO deficiency to repair by dietary copper supplementation may be related to the relatively slow turnover of the affected mitochondria in the terminally differentiated heart.
Johnson
W Thomas
WT
USDA, ARS, GFHNRC, P.O. Box 9034, Grand Forks, ND 58202-9034, USA. tjohnson@gfhnrc.ars.usda.gov
Brown-Borg
Holly M
HM
D000818:Animals; D000831:Animals, Newborn; D003300:Copper / Q000008:administration & dosage / Q000378:metabolism*; D030401:Cytochrome-c Oxidase Deficiency; D004032:Diet; D005260:Female; D006321:Heart / Q000196:embryology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D011247:Pregnancy; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D007527:Isoenzymes; D021122:Protein Subunits; D003300:Copper