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Metabolic adaptation of the fetal and postnatal ovine heart: regulatory role of hypoxia-inducible factors and nuclear respiratory factor-1. Pediatr Res 2002 Aug;52(2):269-78

Date

08/01/2002

Pubmed ID

12149506

DOI

10.1203/00006450-200208000-00021

Scopus ID

2-s2.0-85047682703   33 Citations

Abstract

Numerous metabolic adaptations occur in the heart after birth. Important transcription factors that regulate expression of the glycolytic and mitochondrial oxidative genes are hypoxia-inducible factors (HIF-1alpha and -2alpha) and nuclear respiratory factor-1 (NRF-1). The goal of this study was to examine expression of HIF-1alpha, HIF-2alpha, and NRF-1 and the genes they regulate in pre- and postnatal myocardium. Ovine right and left ventricular myocardium was obtained at four time points: 95 and 140 d gestation (term = 145 d) and 7 d and 8 wk postnatally. Steady-state mRNA and protein levels of HIF-1alpha and NRF-1 and protein levels of HIF-2alpha were measured along with mRNA of HIF-1alpha-regulated genes (aldolase A, alpha- and beta-enolase, lactate dehydrogenase A, liver and muscle phosphofructokinase) and NRF-1-regulated genes (cytochrome c, Va subunit of cytochrome oxidase, and carnitine palmitoyltransferase I ). HIF-1alpha protein was present in fetal myocardium but dropped below detectable levels at 7 d postnatally. HIF-2alpha protein levels were similar at the four time points. Steady-state mRNA levels of alpha-enolase, lactate dehydrogenase A, and liver phosphofructokinase declined significantly postnatally. Aldolase A, beta-enolase, and muscle phosphofructokinase mRNA levels increased postnatally. Steady-state mRNA and protein levels of NRF-1 decreased postnatally in contrast to the postnatal increases in cytochrome c, subunit Va of cytochrome oxidase, and carnitine palmitoyltransferase I mRNA levels. The in vivo postnatal regulation of enzymes encoding glycolytic and mitochondrial enzymes is complex. As transactivation response elements for the genes encoding metabolic enzymes continue to be characterized, studies using the fetal-to-postnatal metabolic transition of the heart will continue to help define the in vivo role of these transcription factors.

Author List

Nau PN, Van Natta T, Ralphe JC, Teneyck CJ, Bedell KA, Caldarone CA, Segar JL, Scholz TD

Author

Jeffrey L. Segar MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adaptation, Physiological
Animals
Animals, Newborn
Basic Helix-Loop-Helix Transcription Factors
DNA, Complementary
DNA-Binding Proteins
Female
Gene Expression Regulation, Developmental
Glycolysis
Heart
Heart Ventricles
Hypoxia-Inducible Factor 1, alpha Subunit
Mitochondria
Myocardium
NF-E2-Related Factor 1
Nuclear Respiratory Factor 1
Nuclear Respiratory Factors
Pregnancy
RNA, Messenger
Sheep
Trans-Activators
Transcription Factors
jenkins-FCD Prod-411 e00897e83867fcfa48419861683711f8d99adb75