Meeting Abstract
P3.99 Thursday, Jan. 6 The Ability of PAS, Acetylsalicylic Acid and Calcium EDTA to Protect Against the Toxic Effects of Manganese on Mitochondrial Respiration and Membrane Potential in the Gill of Crassostrea virginica SADDLER, C.*; DUNCANSON, l.; JOSEPH, J.; CATAPANE, E.J.; CARROLL, M.A.; Medgar Evers; Medgar Evers; Kingsborough Community College; Medgar Evers; Medgar Evers catapane@mec.cuny.edu
Manganese (Mn) is an essential metal that at excessive levels in brain causes Manganism, which is similar to Parkinsons disease. The mechanism of action is not completely understood but may be due to mitochondrial damage and resulting dysfunction of the brain’s dopaminergic system. Previously, we showed lateral cilia of gill of Crassostrea virginica are controlled by serotonergic-dopaminergic innervations from their ganglia and Mn treatments disrupts the cilio-inhibitory dopaminergic system. Here we studied effects of Mn on mitochondrial respiration and membrane potential. We prepared mitochondria from gill and studied respiration and mitochondrial membrane potential using the cationic dye TMRM (Tetramethylrhodamine, methyl ester, perchlorate). We also took time lapse micrographs of gill filaments and mitochondrial smears treated with TMRM. Mn caused dose dependent decreases in O2 consumption, which was blocked by pretreating with calcium disodium EDTA (caEDTA), p-aminosalicylic acid (PAS) or acetylsalicylic acid (ASA). Each partially reversed the toxic effects of Mn when added to Mn treated mitochondria. Mn decreased mitochondrial membrane potentials and was partially blocked by PAS, but not caEDTA. Time lapse photography revealed the fluorescence of specimens treated with Mn dimmed over a 10 minute period indicating a loss of mitochondrial membrane potential. Pretreatment with PAS or ASA prevented the dimming. The study demonstrates that Mn reduces oxygen consumption and disrupts the mitochondrial membrane potential. PAS and ASA protected against both toxic effects and may be a better therapeutic agents than caEDTA in the treatment of Manganism.
