Oxidative stress imbalance n Pulmonary&Cardiovascular disease,Electron paramagnet

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DESCRIPTION (provided by applicant): The overall objective of this research effort is to identify the causes and consequences of nitric oxide and oxidant production imbalances in health and disease, investigate mechanisms of microbial killing by the immune system, study metal homeostasis in cells and how it contributes to cellular proliferation and migration and establish the relevance of redox processes in the differentiation of stem cells. It is currently well-established that oxidant homeostasis and electron transfer reactions are fundamental in maintaining physiological processes in health and that their impairment or dysfunction cause severe phenotypical consequences. Both reduced oxidant bioavailability or overproduction and difficulties in mediating key electron transfer reactions are key factors leading to the impairment of beneficial signal transduction events or inducers of cellular and tissue damage. Oxidant imbalances are becoming recognized contributors of hypertension and cardiovascular complications in diabetes, atherosclerosis, inflammation, male impotence, and important factors contributing to stem cell differentiation and regeneration and cancer onset, progression and prognosis. All of these are human conditions of public health interest. The University of Illinois at Chicago Colleges of Medicine, Dentistry, Pharmacy and Biological Sciences through its diverse departments and research initiatives is currently developing multiple studies and programs dedicated to the understanding of how paramagnetic species that can be tracked, identified and quantified through the use of EPR lead to increased lung permeability in inflammation and sepsis, oxidative stress induced alterations of ventricular function, oxidant mediated vascular remodeling and damage, stem cell differentiation, protein interactions, cancer biology, photosynthesis, microbial killing and drug metabolism. The development of such initiatives depend, at least in part, on our ability to identify which among the many reactive oxygen and nitrogen species are produced at different stages of disease progression, and the precise quantification of reactive species yield, on our capacity to define electron donors and acceptors and track molecular events influencing membrane permeability and interaction with drugs. Electron paramagnetic resonance (EPR) remains the only available technique capable of unequivocally identifying particular paramagnetic species (stable and short lived) based on fingerprint signature resonance spectra and serves the purpose of quantifying the generation of free radical oxidants. For example, it is of pivotal importance to directly identify the sources of superoxide radical anion and nitric oxide that contribute to tissue damage in inflammation and trigger signaling events that contribute to pulmonary edema, hypertension and cardiac failure or trigger events such as stem cell differentiation. At the same time it would be possible to determine how superoxide dismutase enzymes contribute to avoid or promote oxidative stress events warranting or compromising nitric oxide bioavailability. Through spin labeling it would be possible to study membrane microdomain formation and track drug metabolites. Therefore, the acquisition of an EPR instrument would integrate and uniquely contribute for the development of the current initiatives while fostering new collaborative studies putting the departments in the position of making important progress towards the understanding of intricate molecular processes and the development of therapies to re-equilibrate physiological processes at the cellular level.