Methyl mercury inhibition of synaptosome protein synthesis: Role of mitochondrial dysfunction

Abstract

Possible modes of organic mercurial inhibition of synaptosome protein synthesis were investigated. CH 3HgCl inhibited protein synthesis in synaptosomes harvested from both neonatal and adult rat brain cortices. Maximum inhibition occurred when incubations were performed at low synaptosome concentrations (<1 mg/ml). There was only minor release of lactic dehydrogenase at mercurial concentrations producing marked inhibition of protein synthesis. No change was seen in synaptosome volume at 0–100 μ m CH 3HgCl. Incubation of neonatal synaptosomes in a Na +- and K +-containing medium with increasing concentrations of CH 3HgCl produced a decrease in [K +] and increase in Na + content. Addition of CH 3HgCl to a cell-free, K +-dependent protein-synthesizing system containing brain microsomes from neonatal rats inhibited [ 3H]leucine incorporation into protein. Incubation of synaptosomes in the presence of methyl mercury resulted in a dose-dependent decline in ATP. Such a decline in available ATP may account for the observed mercurial inhibition of synaptosomal protein synthesis.