REGULATION OF THE ANTIOXIDANT STATUS OF ENDOTHELIAL CELLS BY MITOCHONDRIA AND AMP-ACTIVATED PROTEIN KINASE ALPHA 1. (360G-Wellcome-086729_Z_08_Z)

We propose to investigate the way in which nitric oxide (NO) contributes to the maintenance of the antioxidant status of vascular endothelial cells. To do this we intend to: 1) study the signalling cascade initiated by the generation of mitochondrial reactive oxygen species (ROS) as a result of the interaction of NO with cytochrome c oxidase at 3% O2; 2) identify the role of AMPK (in particular the catalytic alpha 1 subunit) and redox-responsive transcription factors (e.g. Nrf2, FOXO) in this pathway; 3) explore whether this system maintains a constitutive defensive state in these cells which, if impaired, removes their protection against potentially pathophysiological situations, such as hypoxia and oxidative stress, that occur in conditions such as diabetes or metabolic syndrome.