Disease Progression Mediated by Egr-1 Associated Signaling in Response to Oxidative Stress

When cellular reducing enzymes fail to shield the cell from
increased amounts of reactive oxygen species (ROS), oxidative
stress arises. The redox state is misbalanced, DNA and proteins are
damaged and cellular transcription networks are activated. This
condition can lead to the initiation and/or to the progression of
atherosclerosis, tumors or pulmonary hypertension; diseases that
are decisively furthered by the presence of oxidizing agents. Redox
sensitive genes, like the zinc finger transcription factor early
growth response 1 (Egr-1), play a pivotal role in the
pathophysiology of these diseases. Apart from inducing apoptosis,
signaling partners like the MEK/ERK pathway or the protein kinase C
(PKC) can activate salvage programs such as cell proliferation that
do not ameliorate, but rather worsen their outcome. Here, we review
the currently available data on Egr-1 related signal transduction
cascades in response to oxidative stress in the progression of
epidemiologically significant diseases. Knowing the molecular
pathways behind the pathology will greatly enhance our ability to
identify possible targets for the development of new therapeutic
strategies.