Temporal, spatial, and oxygen-regulated expression of hypoxia-inducible factor-1 in the lung

Aimee Y. Yu, Maria G. Frid, Larissa Shimoda, Charles M Wiener, Kurt Stenmark, Gregg L Semenza

Research output: Contribution to journalArticle

Abstract

Hypoxia-inducible factor (HIF)-1 is a basic helix-loop-helix transcription factor that transactivates genes encoding proteins that participate in homeostatic responses to hypoxia. Several of these downstream gene products, such as erythropoietin, vascular endothelial growth factor, heme oxygenase-1, and inducible nitric oxide synthase, may contribute to the pathogenesis of pulmonary hypertension. Previous studies demonstrated increased HIF-1 mRNA levels in rats and mice subjected to hypoxia. In this study, we have demonstrated spatial, temporal, and O2-dependent expression of HIF-1 protein. Immunoblot analysis revealed hypoxic induction of HIF-1 in all cultured pulmonary cell types assayed, including those derived from pulmonary arterial endothelium and smooth muscle, bronchial epithelium, alveolar macrophages, alveolar epithelium, and microvascular endothelium. In contrast to all other cell types, pulmonary arterial smooth muscle cells expressed HIF-1 under nonhypoxic conditions. Immunohistochemistry and immunoblot analysis of ferret lungs demonstrated pulmonary expression of HIF- 1 in vivo. HIF-1 protein expression was induced maximally when lungs were ventilated with 0 or 1% O2 for 4 h. On reoxygenation, HIF-1 was rapidly degraded, with a half-life of 2 concentration in vivo and are consistent with the involvement of HIF-1 in the physiological and pathophysiological responses to hypoxia in the lung.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume275
Issue number4 19-4
StatePublished - 1998

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Hypoxia-Inducible Factor 1
Oxygen
Lung
Endothelium
Epithelium
Basic Helix-Loop-Helix Transcription Factors
Cell Hypoxia
Ferrets
Proteins
Heme Oxygenase-1
Alveolar Macrophages
Nitric Oxide Synthase Type II
Erythropoietin
Pulmonary Hypertension
Vascular Endothelial Growth Factor A
Smooth Muscle Myocytes
Smooth Muscle
Half-Life
Cultured Cells
Immunohistochemistry

Keywords

  • Gene transcription
  • Pulmonary cells

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

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title = "Temporal, spatial, and oxygen-regulated expression of hypoxia-inducible factor-1 in the lung",
abstract = "Hypoxia-inducible factor (HIF)-1 is a basic helix-loop-helix transcription factor that transactivates genes encoding proteins that participate in homeostatic responses to hypoxia. Several of these downstream gene products, such as erythropoietin, vascular endothelial growth factor, heme oxygenase-1, and inducible nitric oxide synthase, may contribute to the pathogenesis of pulmonary hypertension. Previous studies demonstrated increased HIF-1 mRNA levels in rats and mice subjected to hypoxia. In this study, we have demonstrated spatial, temporal, and O2-dependent expression of HIF-1 protein. Immunoblot analysis revealed hypoxic induction of HIF-1 in all cultured pulmonary cell types assayed, including those derived from pulmonary arterial endothelium and smooth muscle, bronchial epithelium, alveolar macrophages, alveolar epithelium, and microvascular endothelium. In contrast to all other cell types, pulmonary arterial smooth muscle cells expressed HIF-1 under nonhypoxic conditions. Immunohistochemistry and immunoblot analysis of ferret lungs demonstrated pulmonary expression of HIF- 1 in vivo. HIF-1 protein expression was induced maximally when lungs were ventilated with 0 or 1{\%} O2 for 4 h. On reoxygenation, HIF-1 was rapidly degraded, with a half-life of 2 concentration in vivo and are consistent with the involvement of HIF-1 in the physiological and pathophysiological responses to hypoxia in the lung.",
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T1 - Temporal, spatial, and oxygen-regulated expression of hypoxia-inducible factor-1 in the lung

AU - Yu, Aimee Y.

AU - Frid, Maria G.

AU - Shimoda, Larissa

AU - Wiener, Charles M

AU - Stenmark, Kurt

AU - Semenza, Gregg L

PY - 1998

Y1 - 1998

N2 - Hypoxia-inducible factor (HIF)-1 is a basic helix-loop-helix transcription factor that transactivates genes encoding proteins that participate in homeostatic responses to hypoxia. Several of these downstream gene products, such as erythropoietin, vascular endothelial growth factor, heme oxygenase-1, and inducible nitric oxide synthase, may contribute to the pathogenesis of pulmonary hypertension. Previous studies demonstrated increased HIF-1 mRNA levels in rats and mice subjected to hypoxia. In this study, we have demonstrated spatial, temporal, and O2-dependent expression of HIF-1 protein. Immunoblot analysis revealed hypoxic induction of HIF-1 in all cultured pulmonary cell types assayed, including those derived from pulmonary arterial endothelium and smooth muscle, bronchial epithelium, alveolar macrophages, alveolar epithelium, and microvascular endothelium. In contrast to all other cell types, pulmonary arterial smooth muscle cells expressed HIF-1 under nonhypoxic conditions. Immunohistochemistry and immunoblot analysis of ferret lungs demonstrated pulmonary expression of HIF- 1 in vivo. HIF-1 protein expression was induced maximally when lungs were ventilated with 0 or 1% O2 for 4 h. On reoxygenation, HIF-1 was rapidly degraded, with a half-life of 2 concentration in vivo and are consistent with the involvement of HIF-1 in the physiological and pathophysiological responses to hypoxia in the lung.

AB - Hypoxia-inducible factor (HIF)-1 is a basic helix-loop-helix transcription factor that transactivates genes encoding proteins that participate in homeostatic responses to hypoxia. Several of these downstream gene products, such as erythropoietin, vascular endothelial growth factor, heme oxygenase-1, and inducible nitric oxide synthase, may contribute to the pathogenesis of pulmonary hypertension. Previous studies demonstrated increased HIF-1 mRNA levels in rats and mice subjected to hypoxia. In this study, we have demonstrated spatial, temporal, and O2-dependent expression of HIF-1 protein. Immunoblot analysis revealed hypoxic induction of HIF-1 in all cultured pulmonary cell types assayed, including those derived from pulmonary arterial endothelium and smooth muscle, bronchial epithelium, alveolar macrophages, alveolar epithelium, and microvascular endothelium. In contrast to all other cell types, pulmonary arterial smooth muscle cells expressed HIF-1 under nonhypoxic conditions. Immunohistochemistry and immunoblot analysis of ferret lungs demonstrated pulmonary expression of HIF- 1 in vivo. HIF-1 protein expression was induced maximally when lungs were ventilated with 0 or 1% O2 for 4 h. On reoxygenation, HIF-1 was rapidly degraded, with a half-life of 2 concentration in vivo and are consistent with the involvement of HIF-1 in the physiological and pathophysiological responses to hypoxia in the lung.

KW - Gene transcription

KW - Pulmonary cells

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