Date of Award
Dr. David Njus
Oxidative stress is thought to contribute to the death of dopamine neurons and the consequential progression of Parkinson’s disease. Redox cycling of quinones, including compounds formed by dopamine oxidation, can lead to oxidative stress and damaging of the mitochondria. Which enzymes catalyze the redox cycling of quinones is unknown, however. Inhibitors of the mitochondrial respiratory chain (cyanide, rotenone) do not inhibit redox cycling. Mitochondrial NAD(P)H:quinone oxidoreductases are likely candidates, but dicumarol, a common inhibitor of such enzymes is not effective. We observed that Cibacron Blue does indeed inhibit NADH-dependent redox cycling to an extent. Our data shows that the rate of oxygen consumption decreased with the addition of Cibacron Blue. Moreover, the changes in the mitochondrial membrane potential, indicated by fluorescence of the rhodamine dye bound to the membrane, are less significant when the inhibitor was added. Cibacron Blue inhibits a quinone:oxidoreductase enzyme and has important implications for the causes of Parkinson’s disease. Moreover, another inhibitor, mersalyl acid, has also been identified as a potentially more effective blocker to redox cycling, based on the drastic decrease in oxygen consumption upon its addition.
Sebastian, Kiran, "Identification of Enzymes Causing Redox Cycling, Causing Oxidative Stress and Damaging Mitochondria" (2013). Honors College Theses. Paper 13.