GLUTATHIONE TRANSFERASES CATALYZE THE DETOXICATION OF OXIDIZED METABOLITES (O-QUINONES) OF CATECHOLAMINES AND MAY SERVE AS AN ANTIOXIDANT SYSTEM PREVENTING DEGENERATIVE CELLULAR PROCESSES

omicron-Quinones are physiological oxidation products of catecholamine s that contribute to redox cycling, toxicity and apoptosis, i.e. the n eurodegenerative processes underlying Parkinson's disease and schizoph renia. The present study shows that the cyclized omicron-quinones amin ochrome, dopachrome, adrenochrome and noradrenochrome, derived from do pamine, dopa, adrenaline and noradrenaline respectively, are efficient ly conjugated with glutathione in the presence of human glutathione tr ansferase (GST) M2-2. The oxidation product of adrenaline, adrenochrom e, is less active as a substrate for GST M2-2, and more efficiently co njugated by GST M1-1. Evidence for expression of GST M2-2 in substanti a nigra of human brain was obtained by identification of the correspon ding PCR product in a cDNA library. Glutathione conjugation of these q uinones is a detoxication reaction that prevents redox cycling, thus i ndicating that GSTs have a cytoprotective role involving elimination o f reactive chemical species originating from the oxidative metabolism of catecholamines. In particular, GST M2-2 has the capacity to provide protection relevant to the prevention of neurodegenerative diseases.