Hypoxia-Dependent HIF-1 Activation Impacts on Tissue Remodeling in Graves' Ophthalmopathy-Implications for Smoking.

Context: In Graves' ophthalmopathy (GO), inflammation with tissue expansion in a closed compartment like the bony orbit and smoking may cause tissue hypoxia.

Objectives: In this study, we investigated whether hypoxia-inducible factor-1 (HIF-1) action impacts on tissue remodeling in GO with the aim to identify possible new therapeutic targets.

Design/setting/participants: Orbital fibroblasts (OFs) were derived from GO patients and control (Ctrl) persons.

Role of reactive oxygen species in the regulation of HIF-1 by prolyl hydroxylase 2 under mild hypoxia.

The function and survival of eukaryotic cells depends on a constant and sufficient oxygen supply. Cells recognize and respond to hypoxia by accumulation of the transcription factor hypoxia-inducible factor 1 (HIF-1), composed of an oxygen-sensitive HIF-1α and a constitutive HIF-1β subunit. Besides physiology, HIF-1 induction is involved in major pathological processes such as cardiovascular disease, inflammation and cancer, which are associated with the formation of reactive oxygen species (ROS).

Role of N-acetyl-N-nitroso-tryptophan as nitric oxide donor in the modulation of HIF-1-dependent signaling.

N-Acetyl-N-nitroso-tryptophan (NANT) is well known for its capacity to generate nitric oxide (NO)-releasing compounds. It is unknown, however, whether NANT can be successfully applied as a precursor of NO in a complex biological environment such as a cell culture system. NO donors can be useful to induce the transcription factor hypoxia-inducible factor 1 (HIF-1) that coordinates the protection of cells and tissues from the lack of oxygen, termed hypoxia.

Non-hypoxic activation of the negative regulatory feedback loop of prolyl-hydroxylase oxygen sensors.

Hypoxia inducible factors (HIF) coordinate cellular responses towards hypoxia. HIFs are mainly regulated by a group of prolyl-hydroxylases (PHDs) that in the presence of oxygen, target the HIFalpha subunit for degradation. Herein, we studied the role of nitric oxide (NO) in regulating PHD activities under normoxic conditions.