Figure 6.

Proposed pathway by which GSNO can activate HIF 1 through PI3K/Akt in normoxia. This schematic illustrates the proposed regulation of HIF-1 in normoxia by the endogenous S-nitrosothiol, GSNO, through PI3K/Akt activation. In pulmonary vascular endothelial cells and Cos 7 cells, this appears to occur not through classic NO· diffusion with activation of guanylyl cyclase, but through a thiol-based reaction requiring the membrane protein, γGT. One target of this –SNO modification is activation of PI3K. Another target is PTEN, the counter-regulatory phosphatase of the PI3K/Akt pathway.