Herr 2007 Cell Mol Life Sci
| Herr B, Zhou J, DrΓΆse S, BrΓΌne B (2007) The interaction of superoxide with nitric oxide destabilizes hypoxia-inducible factor-1alpha. Cell Mol Life Sci 64:3295-305. |
Herr B, Zhou J, Droese S, Bruene B (2007) Cell Mol Life Sci
Abstract: In renal carcinoma cells (RCC4) hypoxia inducible factor-1 (HIF-1) is constitutively expressed due to a von Hippel Lindau protein deficiency, but can be degraded by calpain, independently of the 26S proteasome, when exposed to hypoxia/nitric oxide (NO). In this study we examined molecular mechanisms to explain calpain activation. The inability of hypoxia/NO to degrade HIF-1Ξ± in respiratory-deficient RCC4-Ο0 cells pointed to the requirement for mitochondria-derived reactive oxygen species. A prerequisite for O2 β in combination with NO to destabilize HIF-1Ξ± was corroborated in RCC4-p0 cells, when the redox cycler 2,3-dimethoxy-1,4-naphthoquinone was used as a source of superoxide. Degradation of HIF-1Ξ± required intracellular calcium transients and calpain activation. Using uric acid to interfere with signal transmission elicited by NO/O2 β blocked HIF-1Ξ± degradation and attenuated a calcium increase. We conclude that an oxidative signal as a result of NO/O2 β coformation triggers a calcium increase that activates calpain to degrade HIF-1Ξ±, independently of the proteasome. β’ Keywords: HIF-1Ξ±, Nitric oxide, Oxygen radicals, Calcium, Calpain, Mitochondria
β’ O2k-Network Lab: DE Frankfurt Droese S
Labels:
Stress:Oxidative stress;RONS
Coupling state: OXPHOS
HRR: Oxygraph-2k
