Hypoxia-inducible factor 1 mediates hypoxia-induced cardiomyocyte lipid accumulation by reducing the DNA binding activity of peroxisome proliferator-activated receptor α/retinoid X receptor

2007 ◽  
Vol 364 (3) ◽  
pp. 567-572 ◽  
Author(s):  
Adam J. Belanger ◽  
Zhengyu Luo ◽  
Karen A. Vincent ◽  
Geoffrey Y. Akita ◽  
Seng H. Cheng ◽  
...  
Keyword(s):  
Dna Binding ◽  
Lipid Accumulation ◽  
Hypoxia Inducible Factor ◽  
Binding Activity ◽  
Retinoid X Receptor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hypoxia Inducible Factor 1 ◽  
Dna Binding Activity

scholarly journals Hypoxia-inducible factor 1 levels vary exponentially over a physiologically relevant range of O2 tension

1996 ◽  
Vol 271 (4) ◽  
pp. C1172-C1180 ◽  
Author(s):  
B. H. Jiang ◽  
G. L. Semenza ◽  
C. Bauer ◽  
H. H. Marti
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
Mammalian Cells ◽  
Functional Characterization ◽  
Hypoxia Inducible Factor ◽  
Binding Activity ◽  
Maximal Response ◽  
Hypoxia Inducible Factor 1 ◽  
Dna Binding Activity

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop-helix protein implicated in the transcriptional activation of genes encoding erythropoietin, glycolytic enzymes, and vascular endothelial growth factor in hypoxic mammalian cells. In this study, we have quantitated HIF-1 DNA-binding activity and protein levels of the HIF-1 alpha and HIF-1 beta subunits in human HeLa cells exposed to O2 concentrations ranging from 0 to 20% in the absence or presence of 1 mM KCN to inhibit oxidative phosphorylation and cellular O2 consumption. HIF-1 DNA-binding activity, HIF-1 alpha protein and HIF-1 beta protein each increased exponentially as cells were subjected to decreasing O2 concentrations, with a half maximal response between 1.5 and 2% O2 and a maximal response at 0.5% O2, both in the presence and absence of KCN. The HIF-1 response was greatest over O2 concentrations associated with ischemic/hypoxic events in vivo. These results provide evidence for the involvement of HIF-1 in O2 homeostasis and represent a functional characterization of the putative O2 sensor that initiates hypoxia signal transduction leading to HIF-1 expression.

scholarly journals Desferrioxamine induces erythropoietin gene expression and hypoxia- inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction

Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3610-3615 ◽  
Author(s):  
GL Wang ◽  
GL Semenza
Keyword(s):  
Signal Transduction ◽  
Dna Binding ◽  
Cobalt Chloride ◽  
De Novo ◽  
Hypoxia Inducible Factor ◽  
Binding Activity ◽  
Ferrous Ammonium Sulfate ◽  
Hypoxia Inducible Factor 1 ◽  
Dna Binding Activity ◽  
Hep3b Cells

Abstract Erythropoietin (EPO) gene transcription is activated in kidney cells in vivo and in Hep3B cells exposed to hypoxia or cobalt chloride. Hypoxia- inducible factor 1 (HIF-1) is a nuclear factor that binds to the hypoxia-inducible enhancer of the EPO gene at a site that is required for transcriptional activation. HIF-1 DNA-binding activity is induced by hypoxia or cobalt chloride treatment of Hep3B cells. We report that treatment of Hep3B cells with desferrioxamine (DFX) induced HIF-1 activity and EPO RNA expression with kinetics similar to the induction of HIF-1 by hypoxia or cobalt chloride. Induction by each of these stimuli was inhibited by cycloheximide, indicating a requirement for de novo protein synthesis. DFX appears to induce HIF-1 by chelating iron as induction was inhibited by coadministration of ferrous ammonium sulfate. DFX administration to mice transiently increased EPO RNA levels in the kidney. As previously shown for hypoxia and cobalt treatment, DFX also induced HIF-1 activity in non-EPO-producing cells, suggesting the existence of a common hypoxia signal-transduction pathway leading to HIF-1 induction in different cell types.

scholarly journals Preterm and infection-driven preterm labor: the role of peroxisome proliferator-activated receptors and retinoid X receptor

Reproduction ◽  
2009 ◽  
Vol 137 (6) ◽  
pp. 1007-1015 ◽  
Author(s):  
Sarah J Holdsworth-Carson ◽  
Michael Permezel ◽  
Greg E Rice ◽  
Martha Lappas
Keyword(s):  
Dna Binding ◽  
Preterm Labor ◽  
Binding Activity ◽  
Retinoid X Receptor ◽  
Peroxisome Proliferator ◽  
Dna Binding Activity ◽  
Ppar Γ ◽  
Peroxisome Proliferator Activated Receptors ◽  
Gestational Tissues ◽  
Expression And Activity

Approximately 8% of births are complicated by preterm delivery. To improve neonatal outcomes, a greater understanding of the mechanisms surrounding preterm parturition is required. Peroxisome proliferator-activated receptors (PPARs) have been implicated in the regulation of labor at term where they exhibit anti-inflammatory properties. Thus, we hypothesize that dysregulation of PPAR expression and activity may be associated with preterm labor and infection-associated preterm labor. The aim of this study was to compare the expression and activity of PPARs and the expression of retinoid X-receptor α (RXRA) in gestational tissues from term and preterm deliveries, and from infection-associated preterm deliveries. Quantitative RT-PCR, western blotting and activity ELISA were used to study expression and DNA binding profiles. Compared with term, preterm parturition was associated with an increased expression of PPAR δ (PPARD; mRNA and protein), PPAR γ (PPARG; protein) and RXRA (protein) in the placenta and PPARD (mRNA and protein) and RXRA (mRNA) in the choriodecidua. There was, however, no change in preterm PPAR DNA binding activity compared with term. Preterm chorioamnionitis (CAM) demonstrated protein degradation in the choriodecidua and was associated with a decline in the mRNA expression of PPAR α (PPARA) and RXRA compared with uninfected preterm cases. PPAR DNA binding activity increased in the placenta (PPARD and PPARG) and decreased in the amnion (PPARA and PPARG) in association with preterm CAM. In conclusion, idiopathic preterm deliveries were associated with an increase in PPAR:RXR expression and preterm CAM was associated with a decrease in PPAR:RXR expression and tissue-specific alterations in transcriptional activity. The reasons for such dysregulation remain to be determined; however, the data are consistent with the hypothesis that PPARs may play a role in preterm labor and infection-complicated preterm deliveries.

Long-term exercise increases the DNA binding activity of peroxisome proliferator–activated receptor γ in rat adipose tissue

Metabolism ◽  
2007 ◽  
Vol 56 (8) ◽  
pp. 1029-1036 ◽  
Author(s):  
Anatoli Petridou ◽  
Sofia Tsalouhidou ◽  
George Tsalis ◽  
Thorsten Schulz ◽  
Horst Michna ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Dna Binding ◽  
Binding Activity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dna Binding Activity ◽  
Rat Adipose Tissue

scholarly journals Desferrioxamine induces erythropoietin gene expression and hypoxia- inducible factor 1 DNA-binding activity: implications for models of hypoxia signal transduction

Blood ◽  
1993 ◽  
Vol 82 (12) ◽  
pp. 3610-3615 ◽  
Author(s):  
GL Wang ◽  
GL Semenza
Keyword(s):  
Signal Transduction ◽  
Dna Binding ◽  
Cobalt Chloride ◽  
De Novo ◽  
Hypoxia Inducible Factor ◽  
Binding Activity ◽  
Ferrous Ammonium Sulfate ◽  
Hypoxia Inducible Factor 1 ◽  
Dna Binding Activity ◽  
Hep3b Cells

Erythropoietin (EPO) gene transcription is activated in kidney cells in vivo and in Hep3B cells exposed to hypoxia or cobalt chloride. Hypoxia- inducible factor 1 (HIF-1) is a nuclear factor that binds to the hypoxia-inducible enhancer of the EPO gene at a site that is required for transcriptional activation. HIF-1 DNA-binding activity is induced by hypoxia or cobalt chloride treatment of Hep3B cells. We report that treatment of Hep3B cells with desferrioxamine (DFX) induced HIF-1 activity and EPO RNA expression with kinetics similar to the induction of HIF-1 by hypoxia or cobalt chloride. Induction by each of these stimuli was inhibited by cycloheximide, indicating a requirement for de novo protein synthesis. DFX appears to induce HIF-1 by chelating iron as induction was inhibited by coadministration of ferrous ammonium sulfate. DFX administration to mice transiently increased EPO RNA levels in the kidney. As previously shown for hypoxia and cobalt treatment, DFX also induced HIF-1 activity in non-EPO-producing cells, suggesting the existence of a common hypoxia signal-transduction pathway leading to HIF-1 induction in different cell types.

scholarly journals Echinomycin, a Small-Molecule Inhibitor of Hypoxia-Inducible Factor-1 DNA-Binding Activity

2005 ◽  
Vol 65 (19) ◽  
pp. 9047-9055 ◽  
Author(s):  
Dehe Kong ◽  
Eun Jung Park ◽  
Andrew G. Stephen ◽  
Maura Calvani ◽  
John H. Cardellina ◽  
...  
Keyword(s):  
Dna Binding ◽  
Small Molecule ◽  
Hypoxia Inducible Factor ◽  
Small Molecule Inhibitor ◽  
Binding Activity ◽  
Hypoxia Inducible Factor 1 ◽  
Dna Binding Activity ◽  
Molecule Inhibitor
Sign in / Sign up

Export Citation Format

Share Document