Perivenous expression of the mRNA of the three hypoxia-inducible factor α-subunits, HIF1α, HIF2α and HIF3α, in rat liver

Kietzmann, Thomas; Cornesse, Yvonne; Brechtel, Katja; Modaressi, Said; Jungermann, Kurt

doi:10.1042/0264-6021:3540531

Cited by 115 publications

(108 citation statements)

References 34 publications

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“…Our data suggest that the stabilization of HIF-α protein precedes an increase in HIF-α transcription. The induction in HIF-3α and HIF-1α mRNA in A549 cells in response to hypoxia indicates that the regulatory response of HIF-α may also occur at the mRNA level, which is consistent with the results obtained in in vivo experiments showing mRNA of HIF-3α and HIF-1α was predominantly expressed in the perivenous zone of the liver [32]. High steady-state mRNA levels of HIF-3α were achieved in alveolar epithelial cells during sustained hypoxia.…”

Section: Discussionsupporting

confidence: 90%

“…To date, expression has only been studied at the mRNA level of whole-organ homogenates [24,31]. These studies emphasized organ expression in adult rat, although different human tissues including lung were shown to express HIF-3α mRNA [32,33,34]. This study demonstrates that when cells were exposed to 1% oxygen for 2 h, a major increase in HIF-3α and HIF-1α protein was observed, whereas HIF-1α protein levels decreased from 8 to 16 h. In addition to the decrease in HIF-1α protein, hypoxia also induced a decrease in HIF-1α mRNA.…”

Section: Discussionmentioning

confidence: 99%

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Hypoxia upregulates hypoxia inducible factor (HIF)-3α expression in lung epithelial cells: characterization and comparison with HIF-1α

et al. 2006

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The role of the hypoxia-inducible factor (HIF) subunits 1α and 2α in response to hypoxia is well established in lung epithelial cells, whereas little is known about HIF-3α with respect to transcriptional and translational regulation by hypoxia. HIF-3α and HIF-1α are two similar but distinct basic helix-loop-helix-PAS proteins, which have been postulated to activate hypoxia responsive genes in response to hypoxia. Here, we used quantitative real time RT-PCR and immunoblotting to determine the activation of HIF-3α vs. HIF-1α by hypoxia. HIF-3α was strongly induced by hypoxia (1% O 2 ) both at the level of protein and mRNA due to an increase in protein stability and transcriptional activation, whereas HIF-1α protein and mRNA levels enhanced transiently and then decreased because of a reduction in its mRNA stability in A549 cells, as measured on mRNA and protein levels. Interestingly, HIF-3α and HIF-1α exhibited strikingly similar responses to a variety of activating or inhibitory pharmacological agents. These results demonstrate that HIF-3α is expressed abundantly in lung epithelial cells, and that the transcriptional induction of HIF-3α plays an important role in the response to hypoxia in vitro. Our findings suggest that HIF-3α, as a member of the HIF system, is complementary rather than redundant to HIF-1α induction in protection against hypoxic damage in alveolar epithelial cells.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Hypoxia upregulates hypoxia inducible factor (HIF)-3α expression in lung epithelial cells: characterization and comparison with HIF-1α

et al. 2006

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“…HIF-1␣, HDAC7, and p300 Form a Complex-The C-TAD of HIF-1␣ has been shown to bind with transcriptional co-activators via the CH1 domain in the N-terminal domain of CBP and p300 (6,12). To determine whether HDAC7, HIF-1␣, and p300/ CBP form a complex or whether there is competition for binding between these proteins, yeast three-hybrid experiments were performed.…”

Section: Hdac7 Increases Hif-1␣ Activity 41968mentioning

confidence: 99%

Histone Deacetylase 7 Associates with Hypoxia-inducible Factor 1α and Increases Transcriptional Activity

Kato¹,

Tamamizu-Kato²,

Shibasaki

2004

Journal of Biological Chemistry

188

155

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“…HIF-1 is involved in hypoxia-dependent induction of a variety of genes, including erythropoietin, glycolytic enzymes, but also plasminogen activator inhibitor-1 and vascular endothelial growth factor (14 -18). Two other HIF ␣-subunits, HIF-2␣ (EPAS/HLF/ HRF/MOP2) (18 -21), and HIF-3␣ (22,23) have been cloned from human, mouse, and rat, and together with other ARNT isoforms (ARNT2 and ARNT3/BMAL-1/MOP-3), they give rise to the existence of several HIF dimers composed of different HIF ␣-subunits and ARNT isoforms (18,24). Interestingly HIF-␣ protein levels and transcriptional activity have been shown to be enhanced by insulin (25)(26)(27).…”

mentioning

confidence: 99%

The Transcription Factors HIF-1 and HNF-4 and the Coactivator p300 Are Involved in Insulin-regulated Glucokinase Gene Expression via the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway

Roth

Curth

Unterman

et al. 2004

Journal of Biological Chemistry

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104

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Glucokinase plays a key role in the regulation of glucose utilization in liver and its expression is strongly enhanced by insulin and modulated by venous pO 2 . In primary rat hepatocytes, pO 2 modulated insulindependent glucokinase (GK) gene expression was abolished by wortmannin an inhibitor of phosphatidylinositol 3-kinase (PI3K). Transfection of vectors encoding the p110 catalytic subunit of PI3K or constitutively active proteinkinase B (PKB) stimulated GK mRNA and protein expression. The transfection of GK promoter constructs together with expression vectors for p110 or constitutively active PKB revealed that the GK promoter region ؊87/؊80 mediates the response to PI3K/PKB. Transfection experiments and gel shift assays show that this element is able to bind hypoxia-inducible factor-1 (HIF-1) in a hypoxia-and PKB-dependent manner. The ability of HIF-1␣ to activate the GK promoter was enhanced by hepatocyte nuclear factor-4␣ (HNF-4␣), acting via the sequence ؊52/؊39, and by the coactivator p300. Stimulation of the GK promoter by insulin was dependent on the intact ؊87/؊80 region and maximal stimulation was achieved when HIF-1␣, HNF-4, and p300 were cotransfected with the ؊1430 GK promoter Luc construct in primary hepatocytes. Maximal stimulation of GK promoter activity by insulin was inhibited when a p300 vector was used containing a mutation within a PKB phosphorylation site. Thus, a regulatory transcriptional complex consisting of HIF-1, HNF-4, and p300 appears to be involved in insulin-dependent GK gene activation.

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Perivenous expression of the mRNA of the three hypoxia-inducible factor α-subunits, HIF1α, HIF2α and HIF3α, in rat liver

Cited by 115 publications

References 34 publications

Hypoxia upregulates hypoxia inducible factor (HIF)-3α expression in lung epithelial cells: characterization and comparison with HIF-1α

Hypoxia upregulates hypoxia inducible factor (HIF)-3α expression in lung epithelial cells: characterization and comparison with HIF-1α

Histone Deacetylase 7 Associates with Hypoxia-inducible Factor 1α and Increases Transcriptional Activity

The Transcription Factors HIF-1 and HNF-4 and the Coactivator p300 Are Involved in Insulin-regulated Glucokinase Gene Expression via the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway

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