| First Author | Swain L | Year | 2014 |
| Journal | J Leukoc Biol | Volume | 96 |
| Issue | 3 | Pages | 365-75 |
| PubMed ID | 24626957 | Mgi Jnum | J:218623 |
| Mgi Id | MGI:5618055 | Doi | 10.1189/jlb.2HI1013-533R |
| Citation | Swain L, et al. (2014) Prolyl-4-hydroxylase domain 3 (PHD3) is a critical terminator for cell survival of macrophages under stress conditions. J Leukoc Biol 96(3):365-75 |
| abstractText | On a molecular level, cells sense changes in oxygen availability through the PHDs, which regulate the protein stability of the alpha-subunit of the transcription 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(-/-) mice were created and analyzed. PHD3(-/-) BMDM showed no altered HIF-1alpha or HIF-2alpha stabilization or increased HIF target gene expression in normoxia or hypoxia. Macrophage M1 and M2 polarization was unchanged likewise. Compared with macrophages from WT littermates, PHD3(-/-) BMDM exhibited a significant reduction in TUNEL-positive cells after serum withdrawal or treatment with stauro and 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 Angptl2 expression was reduced in PHD3(-/-) BMDM under stress conditions. Addition of rAngptl2 rescued the antiapoptotic phenotype, demonstrating that it is involved in the PHD3-mediated response toward apoptotic stimuli in macrophages. |
