HIF-1 and HIF-2 Transcription Factors - Similar but Not Identical

Łoboda, Agnieszka; Józkowicz, Alicja; Dulak, Józef

doi:10.1007/s10059-010-0067-2

Cited by 368 publications

(325 citation statements)

References 76 publications

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“…Moreover, HIF-2α is only expressed in certain tissues [43], while HIF-1α is ubiquitously expressed. Overall their biological actions in response to hypoxia are distinct, as reviewed by Loboda and colleagues [44]. For example, HIF-1α, but not HIF-2α regulates the transcription of genes encoding enzymes involved in glycolysis [45], while HIF-2α has been associated with adaptation to high altitude exposure [46].…”

Section: Hif-1 Proteins and Hypoxic Regulationmentioning

confidence: 99%

The Interaction Between Redox and Hypoxic Signalling Pathways in the Dynamic Oxygen Environment of Cancer Cells

Bhatia¹,

Karlenius²,

Trapani³

et al. 2013

Carcinogenesis

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Section: Hif-1 Proteins and Hypoxic Regulationmentioning

confidence: 99%

The Interaction Between Redox and Hypoxic Signalling Pathways in the Dynamic Oxygen Environment of Cancer Cells

Bhatia¹,

Karlenius²,

Trapani³

et al. 2013

Carcinogenesis

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“…Hypoxia activates hypoxia inducible factor 1 (HIF-1), a heterodimeric transcription factor comprised of α (inducible) and β (ubiquitous) subunits (Loboda et al, 2010). Under hypoxic conditions, HIF-1α is stabilized and translocated to the nucleus.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Inducible Factor-1α Directly Induces the Expression of Receptor Activator of Nuclear Factor-κB Ligand in Periodontal Ligament Fibroblasts

Park

Baek

Lee

et al. 2011

Molecules and Cells

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During orthodontic tooth movement, local hypoxia and enhanced osteoclastogenesis are observed in the compression side of periodontal tissues. The receptor activator of nuclear factor-κB ligand (RANKL) is an osteoblast/ stromal cell-derived factor that is essential for osteoclastogenesis. In this study, we examined the effect of hypoxia on RANKL expression in human periodontal ligament fibroblasts (PDLFs) to investigate the relationship between local hypoxia and enhanced osteoclastogenesis in the compression side of periodontal tissues. Hypoxia significantly enhanced the levels of RANKL mRNA and protein as well as hypoxia inducible factor-1α (HIF-1α) protein in PDLFs. Constitutively active HIF-1α alone significantly increased the levels of RANKL expression in PDLFs under normoxic conditions, whereas dominant negative HIF-1α blocked hypoxia-induced RANKL expression. To investigate further whether HIF-1α directly regulates RANKL transcription, a luciferase reporter assay was performed using the reporter vector containing the RANKL promoter sequence. Exposure to hypoxia or overexpression of constitutively active HIF-1α significantly increased RANKL promoter activity, whereas dominant negative HIF-1α blocked hypoxia-induced RANKL promoter activity. Furthermore, mutations of putative HIF-1α binding elements in RANKL promoter prevented hypoxia-induced RANKL promoter activity. The results of chromatin immunoprecipitation showed that hypoxia or constitutively active HIF-1α increased the DNA binding of HIF-1α to RANKL promoter. These results suggest that HIF-1α mediates hypoxia-induced up-regulation of RANKL expression and that in compression side periodontal ligament, hypoxia enhances osteoclastogenesis, at least in part, via an increased RANKL expression in PDLFs.

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“…9 Under hypoxic conditions, the hypoxia inducible factor 1 (HIF-1), a transcription factor, is activated to regulate its target genes because of the up-regulation of HIF-1a and its subsequent transfer to nuclei. 16 The present study demonstrated that the RANKL/OPG ratio and HIF-1a expression of PDLCs are enhanced by hypoxic treatment, leading to Figure 4. TRAP staining of the coculture systems after a 10-day culture with conditioned media from PDLCs subjected to hypoxia and/or compression in a period of 6, 24, and 72 hours (340).…”

Section: Discussionmentioning

confidence: 59%

Compression and hypoxia play independent roles while having combinative effects in the osteoclastogenesis induced by periodontal ligament cells

Yang

et al. 2015

The Angle Orthodontist

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Objective: To investigate the isolated and combined effects of compression and hypoxia on the osteoclastogenesis induced by periodontal ligament cells (PDLCs). Materials and Methods: A periodontal ligament tissue model (PDLtm) was established by 3-D culturing human PDLCs on a thin sheet of poly lactic-co-glycolic acid scaffold. The PDLtm was treated with hypoxia and/or compression for 6, 24, or 72 hours. After that, a real-time polymerase chain reaction was used for gene expression analysis. The conditioned media were used for the coculture of osteoblast and osteoclast (OC) precursors; tartrate-resistant acid phosphatase staining was done to examine OC formation. Results: Either compression or hypoxia alone significantly up-regulated the gene expression of pro-osteoclastogenic cytokines in the PDLtm and enhanced osteoclastogenesis in the cocultures, and the combination of the two had significantly stronger effects than either stimulation alone. In addition, comparing the two stimulants, we found that the osteoclastogenic property of the PDLCs peaked earlier (at 6 hours) in the compression group than in the hypoxia group (at 24 hours). Conclusions: Both compressive force and hypoxia may take part in initiating osteoclastogenesis in orthodontic tooth movement and may have combinatory effects, which could update our concepts of the mechanisms involved in the initiation of bone resorption on the pressure side of the tooth in question. (Angle Orthod. 2016;86:66-73.)

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HIF-1 and HIF-2 Transcription Factors - Similar but Not Identical

Cited by 368 publications

References 76 publications

The Interaction Between Redox and Hypoxic Signalling Pathways in the Dynamic Oxygen Environment of Cancer Cells

The Interaction Between Redox and Hypoxic Signalling Pathways in the Dynamic Oxygen Environment of Cancer Cells

Hypoxia Inducible Factor-1α Directly Induces the Expression of Receptor Activator of Nuclear Factor-κB Ligand in Periodontal Ligament Fibroblasts

Compression and hypoxia play independent roles while having combinative effects in the osteoclastogenesis induced by periodontal ligament cells

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