Meeting Abstract
P3.53 Wednesday, Jan. 6 Toxic Effects of Manganese on Mitochondrial Respiration and Mitochondrial Membrane Potential in Gill of the Bivalve Crassostrea virginica CRAWFORD, S.*; SADDLER, C.; CATAPANE, E.J.; CARROLL, M.A.; Medgar Evers College, Brooklyn catapane@mec.cuny.edu
Manganese (Mn) is an essential metal that at high levels in brain produces Manganism. The mechanism of action of is not completely understood but may be related to oxidative stress and damage to dopaminergic systems in people. Previously, we showed cilia of lateral cells of gill of Crassostrea virginica are controlled by serotonergic-dopaminergic nerves. Mn disrupts the cilio-inhibitory dopaminergic system. We studied effects of Mn on mitochondria from gill using a YSI Micro-Biological Oxygen Monitor. Mn caused dose dependent decreases in O2 consumption that was blocked by pretreating with 1 mM of calcium disodium EDTA (EDTAca) or p-Aminosalicylic Acid (PAS). Both drugs are being tested as therapeutic agents for Manganism. Adding EDTAca or PAS to Mn treated mitochondria partially reversed the toxic effects of Mn. In other experiments we studied effects of Mn on mitochondrial membrane potentials using the anionic oxonol-based membrane potential-sensitive fluorescent dye, HLB021-152, which increases fluorescent intensity upon depolarization of the mitochondrial membrane. Fluorescence was measured in a Molecular Devices SpectraMax M5 Plate Reader. Mn decreased mitochondrial membrane potential. The decrease was partially blocked by co-treatment with PAS. The study shows Mn reduces oxygen consumption and causes depolarization of mitochondrial membrane potentials. The EDTAca was an effective blocker against the effects of Mn and may be beneficial in reversing negative effects of Mn accumulations. The ability of PAS to ameliorate symptoms of Manganism is postulated to be related to its chelating actions and our results corroborated this. The work was supported by grants 2R25GM06003-05 of NIGMS, 0516041071 of NYSDOE, 0622197 of NSF and P382A080040 of the USDE.
