Impact of Short-Term Systemic Hypoxia on Phagocytosis, Cytokine Production, and Transcription Factor Activation in Peripheral Blood Cells

Figure 8

Proposed mechanism of hypoxia on HIF-1 and NFκB activation in PBMC. Hypoxia causes a reduction of hydroxylase activity leading on the one hand to the activation of NFκB and a consecutive transport of the p50/p65 complex into the nucleus. Binding of p50/p65 to the corresponding promotor side of the HIF-1α gene results in an increase of HIF-1α protein in the cytosol. On the other hand, reduced hydroxylase activity prevents HIF-1α degradation by the proteasome increasing cytosolic HIF-1α concentration. Under hypoxic conditions equivalent to a height of 5500 m, an increase of cytosolic HIF-1α did not raise the HIF-1α concentration in the nucleus indicating that not only the HIF-1 concentration in the cytosol, but also the transport into the nucleus is regulated.