Metabolic adaptation of the fetal and postnatal ovine heart: regulatory role of hypoxia-inducible factors and nuclear respiratory factor-1

Peter N Nau; Timothy Van Natta; J Carter Ralphe; Cynthia J Teneyck; Kurt A Bedell; Christopher A Caldarone; Jeffrey L Segar; Thomas D Scholz

doi:10.1203/00006450-200208000-00021

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Metabolic adaptation of the fetal and postnatal ovine heart: regulatory role of hypoxia-inducible factors and nuclear respiratory factor-1

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Metabolic adaptation of the fetal and postnatal ovine heart: regulatory role of hypoxia-inducible factors and nuclear respiratory factor-1

Peter N Nau, Timothy Van Natta, J Carter Ralphe, Cynthia J Teneyck, Kurt A Bedell, Christopher A Caldarone, Jeffrey L Segar and Thomas D Scholz

Pediatric research, Vol.52(2), pp.269-278

08/2002

DOI: 10.1203/00006450-200208000-00021

PMID: 12149506

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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.

Mitochondria - enzymology

Heart - embryology

Heart - physiology

RNA, Messenger - analysis

Nuclear Respiratory Factors

Hypoxia-Inducible Factor 1, alpha Subunit

DNA-Binding Proteins - metabolism

Glycolysis - physiology

Gene Expression Regulation, Developmental

Myocardium - metabolism

Trans-Activators - genetics

Female

Basic Helix-Loop-Helix Transcription Factors

Nuclear Respiratory Factor 1

Animals, Newborn

Adaptation, Physiological - physiology

Transcription Factors - genetics

DNA-Binding Proteins - genetics

Pregnancy

Transcription Factors - metabolism

Animals

NF-E2-Related Factor 1

Sheep

Trans-Activators - metabolism

Heart Ventricles - metabolism

DNA, Complementary

Details

Title: Subtitle: Metabolic adaptation of the fetal and postnatal ovine heart: regulatory role of hypoxia-inducible factors and nuclear respiratory factor-1
Creators: Peter N Nau - Department of Pediatrics, Division of Pediatric Cardiology, University of Iowa, Iowa City 52242, USA
Timothy Van Natta
J Carter Ralphe
Cynthia J Teneyck
Kurt A Bedell
Christopher A Caldarone
Jeffrey L Segar
Thomas D Scholz
Resource Type: Journal article
Publication Details: Pediatric research, Vol.52(2), pp.269-278
DOI: 10.1203/00006450-200208000-00021
PMID: 12149506
NLM abbreviation: Pediatr Res
ISSN: 0031-3998
eISSN: 1530-0447
Publisher: United States
Grant note: T32 HL007413 / NHLBI NIH HHS R01 HL64770 / NHLBI NIH HHS R29 HL56633 / NHLBI NIH HHS
Language: English
Date published: 08/2002
Academic Unit: Microbiology and Immunology; Cardiology; Stead Family Department of Pediatrics; Surgery; Child and Community Health
Record Identifier: 9984051764402771

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