IN VITRO METHYL MERCURY INHIBITION OF PROTEIN SYNTHESIS IN NEONATAL CEREBELLAR PERIKARYA

Abstract

In an effort to characterize the principal mechanism(s) underlying the methyl mercury-induced defect in protein synthesis in vivo and in vitro, we examined the dose and time related effects of methyl mercury chloride (MeHg) on a variety of cellular functions using bulk-isolated neonatal cerebellar perikarya. This cell preparation demonstrated a high specific activity for protein synthesis which was optimal between 6 and 12 days of age and declined rapidly thereafter. In vitro MeHg inhibited synthesis with an ID₅₀ of - 14 μm without causing significant release of lactate dehydrogenase. The inhibition of protein synthesis occurred independently of mercurial effects on RNA synthesis, mitochondrial function, ATP content or intracellular levels of Na⁺ and K⁺. Uptake of [³H]-phenylalanine was not appreciably affected by MeHg. The accumulated evidence suggests that in this in vitro cell model, MeHg inhibition of protein synthesis occurs via a direct interaction with the protein synthetic machinery.