| First Author | Emerling BM | Year | 2005 |
| Journal | Mol Cell Biol | Volume | 25 |
| Issue | 12 | Pages | 4853-62 |
| PubMed ID | 15923604 | Mgi Jnum | J:99131 |
| Mgi Id | MGI:3581328 | Doi | 10.1128/MCB.25.12.4853-4862.2005 |
| Citation | Emerling BM, et al. (2005) Mitochondrial reactive oxygen species activation of p38 mitogen-activated protein kinase is required for hypoxia signaling. Mol Cell Biol 25(12):4853-62 |
| abstractText | Mammalian cells have the ability to sense low oxygen levels (hypoxia). An adaptive response to hypoxia involves the induction of the transcription factor hypoxia-inducible factor 1 (HIF-1). The intracellular signaling pathways that regulate HIF-1 activation during hypoxia remain unknown. Here, we demonstrate that p38alpha-/- cells fail to activate HIF-1 under hypoxic conditions. Cells deficient in Mkk3 and Mkk6, the upstream regulators of p38alpha, also fail to activate HIF-1 under hypoxic conditions. The p38alpha-/- cells are able to activate HIF-1 in response to anoxia or iron chelators during normoxia. Furthermore, the hypoxic activation of p38alpha and HIF-1 was abolished by myxothiazol, a mitochondrial complex III inhibitor, and glutathione peroxidase 1 (GPX1), a scavenger of hydrogen peroxide. Thus, the activation of p38alpha and HIF-1 is dependent on the generation of mitochondrial reactive oxygen species. These results provide genetic evidence that p38 mitogen-activated protein kinase signaling is essential for HIF-1 activation. |
