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| Status |
Public on Dec 31, 2014 |
| Title |
Prolyl-4-hydroxylase domain 3 (PHD3) is a critical terminator for cell survival of macrophages under stress conditions |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
On molecular level cells sense changes in oxygen availability through the prolyl-4-hydroxylase domain enzymes (PHDs), which regulate the protein stability of the α-subunit of the transcription factor hypoxia inducible factor (HIF). Especially PHD3 has been additionally associated with apoptotic cell death. We hypothesized that PHD3 plays a role in cell-fate decisions in macrophages. Therefore myeloid-specific PHD3 knock out mice (PHD3-/-) were created and analysed. PHD3-deficient bone marrow-derived macrophages (BMDM) showed no altered HIF-1alpha or HIF-2alpha stabilization or increased HIF target genes expression in normoxia or hypoxia. Macrophage M1 and M2-polarization was unchanged likewise. Compared to macrophages from wild type littermates PHD3-/- BMDM exhibited a significant reduction in TUNEL positive cells after serum withdrawal or treatment with staurosporine and s-nitroso-N-acetylpenicillamine (SNAP). Under the same conditions PHD3-/- BMDM also showed less Annexin V staining which is representative for membrane disruption and indicated a reduced early apoptosis. In an unbiased transcriptome screen we found that angiopoietin like protein 2 (Angptl2) expression was reduced in PHD3-/- BMDM under stress conditions. Addition of recombinant Angptl2 rescued the anti-apoptotic phenotype demonstrating that it is involved in the PHD3-mediated response towards apoptotic stimuli in macrophages.
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| Overall design |
3 mice each for control wildtype and knockout mice, low/normal oxygen concentration, starved/normal feeding
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| Contributor(s) |
Swain L, Wottawa M, Hillemann A, Beneke A, Odagiri H, Terada K, Endo M, Oike Y, Farhat K, Katschinski DM |
| Citation missing |
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| |
| Submission date |
Mar 07, 2014 |
| Last update date |
Nov 01, 2017 |
| Contact name |
Gabriela Salinas |
| E-mail(s) |
[email protected]
|
| Organization name |
Universitaetsmedizin Goettingen
|
| Department |
Department of Pathology
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| Lab |
NGS Integrative Genomics
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| Street address |
Kreuzbergring 57
|
| City |
Goettingen |
| State/province |
Lower-Saxony |
| ZIP/Postal code |
37075 |
| Country |
Germany |
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| Platforms (1) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA240564 |
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