Nitric oxide inhibits HIF-1alpha protein accumulation under hypoxic conditions: implication of 2-oxoglutarate and iron.

Cells exposed to low oxygen conditions respond by initiating defense mechanisms, including the stabilization of hypoxia-inducible factor (HIF) 1alpha, a transcription factor that upregulates genes such as those involved in angiogenesis and glycolysis, which also plays a pivotal role in the regulation of cellular utilization of oxygen and is an essential regulator of angiogenesis in solid tumor and ischemic disorders. Nitric oxide and other inhibitors of mitochondrial respiration prevent the stabilization of HIF-1alpha during hypoxia. In the present study we found that nitric oxide inhibits HIF-1alpha accumulation under low oxygen (1%) conditions.

S-nitrosation of thioredoxin in the nitrogen monoxide/superoxide system activates apoptosis signal-regulating kinase 1.

In the present study, we have investigated S-nitrosation of reactive thioredoxin (Trx) thiol groups in nitric oxide/superoxide system. We have found that Trx thiol groups are the targets for S-nitrosation by N2O3-like species generated in the system containing xanthine/xanthine oxidase (superoxide producing system) and DEA/NO-the *NO donating compound, however, they have shown low sensitivity to the *NO derived from DEA/NO. N2O3-dependent S-nitrosation of Trx at approximately 2-fold of NO excess compared to the superoxide amount resulted in dissociation and activation of apoptosis signal regulating kinase 1 (ASK1).