Mechanisms of hypoxic signal transduction regulated by reactive nitrogen species.

Recent reports devoted to the field of oxygen sensing outline that signalling molecules such as nitric oxide/nitric oxide derived species as well as cytokines and other inflammatory mediators participate in hypoxic signal transduction. In the present review, we summarize the current knowledge about the role of nitric oxide and reactive nitrogen species (RNS) derived from it in hypoxic signal transduction and particularly in accumulation/de-accumulation of hypoxia inducible factor 1 alpha (HIF-1alpha) protein, which is critical not only for cellular adaptation to low oxygen availability but also for generation of inflammatory and innate immune responses. After brief description of nitric oxide and other RNS as multifunctional messengers we analyse and discuss the RNS-dependent accumulation of HIF-1alpha protein under normoxia followed by discussion of the mechanisms of nitric oxide (NO)-dependent enzyme-regulated degradation of HIF-1alpha protein under low oxygen availability.