Developmental regulation of the alpha-glycerophosphate shuttle in porcine myocardium.
The alpha-glycerophosphate (alpha-GP) shuttle has been shown to play a role in reducing equivalent transfer in neonatal cardiac mitochondria. In adult heart mitochondria, alpha-GP shuttle activity is not detectable. The goals of the current study were to define the time course of the age-dependent decline in alpha-GP shuttle capacity and to identify the enzymatic step(s) of the alpha-GP shuttle which are regulated during development. Intact mitochondria were isolated from porcine hearts of various ages and assayed for alpha-GP shuttle capacity. By 5 weeks of age, alpha-GP shuttle capacity had decreased by nearly 39%. The cytosolic step of the shuttle, catalysed by cytosolic alpha-glycerophosphate dehydrogenase (c alpha-GPDH), demonstrated a significant increase between 0-2-day-old animals and adults. Partial cDNA clones of porcine c alpha-GPDH and mitochondrial alpha-glycerophosphate dehydrogenase (m alpha-GPDH) were prepared and used to quantitate expression of these genes. Using mRNA isolated from neonatal and adult porcine myocardium, expression of the c alpha-GPDH was unchanged, while expression of the m alpha-GPDH gene was present in neonatal but absent in adult myocardium. These results demonstrate a rapid postnatal decline in myocardial alpha-GP shuttle capacity which appears to be regulated by a decline in m alpha-GPDH gene expression.
Scholz
T D
TD
Department of Pediatrics, University of Iowa, Iowa City 52242, USA.
Koppenhafer
S L
SL
TenEyck
C J
CJ
Schutte
B C
BC
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D015152:Blotting, Northern; D002237:Carbohydrate Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D018076:DNA, Complementary; D018507:Gene Expression Regulation, Developmental; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+); D005993:Glycerolphosphate Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D005994:Glycerophosphates / Q000378:metabolism*; D006321:Heart / Q000254:growth & development; D008929:Mitochondria, Heart / Q000378:metabolism; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D012689:Sequence Homology, Nucleic Acid; D013552:Swine
D018076:DNA, Complementary; D005994:Glycerophosphates; C029620:alpha-glycerophosphoric acid; D002237:Carbohydrate Dehydrogenases; D005993:Glycerolphosphate Dehydrogenase; D050536:Glycerol-3-Phosphate Dehydrogenase (NAD+); C056470:3-glycerophosphate dehydrogenase