The Endothelial ADMA/NO Pathway in Hypoxia-Related Chronic Respiratory Diseases

Figure 2

S-nitrosylation of HIF-𝛼 and pVHL. (a) In the presence of oxygen proline, residues of HIF-𝛼 are hydroxylated. This leads to the polyubiquitination of the pVHL-HIF-𝛼 complex resulting in the proteasomal degradation of HIF-𝛼. (b) S-nitrosylation of HIF-𝛼 prevents the binding of pVHL and thereby the polyubiquitination of HIF-𝛼. S-nitrosylation of pVHL also inhibits the ability to mediate the polyubiquitination of HIF-𝛼. In both cases HIF-𝛼 is not degraded but translocated into the nucleus, dimerizes with the HIF-𝛽 subunit, and induces the transcriptional activation of target genes.

(a)

(b)