Cecilia Giulivi, Ph.D.
Molecular Pharmacology and Toxicology
Biochemistry of Free Radicals
Oxygen radicals, produced during the normal oxidatve metabolism, are reactive species that may lead to cellular damage through the reaction with several biomolecules. In this regard, modification of proteins or DNA by oxygen active species may lead to cell dysfunction.
My current research is centered on the molecular basis of pathophysiological processes that modify the mitochondrial production of free radicals, nitric oxide and oxygen radicals. The study includes in vitro studies fo-cusing on the steady state concentration of oxygen free radicals in mitochondria that leads to accumulated damage in mito-chondrial DNA. Several oxidative stress conditions are tested, and eventually related to markers of DNA damage. This work will start a novel area of study in the free radicals field, which bears several pathological and physio-logical implications.
Mechanistic studies on protein inactivation are performed using different oxygen active species generating systems in chemical and biological models. Long term goals are based on the fate of these modified proteins including the possible recovery through antioxidants or eventually, their degradation by intracellular enzymes. Special attention is devoted to myoglobin and hemoglobin because of their important role in the transport and storage of oxygen. Exposure of these proteins to oxygen radicals results in the formation of relatively long lived radicals that may play a role in tissue damage. These radicals are followed by electron paramagnetic resonance in conjunction with different techniques that contribute to the understanding of the radical localization and reactivity.
- Giulivi, C. and Davies, K. J. A. (1990) A novel antioxidant role for hemoglobin: The comproportionation reaction of ferrylhemoglobin with oxyhemoglobin. J. Biol. Chem. 265, 19453-19460.
- Giulivi, C. and Davies, K. J. A. (1993) Dityrosine and tyrosine oxidation products are endogenous markers for selective proteolysis of oxidatively modified red blood cell hemoglobin by the (19S) proteasome. J. Biol. Chem. 268, 8752-8759.
- Giulivi, C., Boveris, A. ,and Cadenas, E. (1995) Hydroxyl radical generation during mitochondrial electron transfer and the formation of 8-hydroxy-desoxyguanosine in mitochondrial DNA. Arch. Biochem. Biophys. 316, 909-916.