Altered sensitivity of posttranslationally modified microtubules to methylmercury in differentiating embryonal carcinoma-derived neurons

Toxicology and Applied Pharmacology
R D GraffK R Reuhl

Abstract

The effects of methylmercury (MeHg) on microtubules (MTs) in differentiating neurons derived from retinoic acid-induced embryonal carcinoma (EC) cells in culture were examined by immunofluorescence microscopy. Undifferentiated EC cells contained mostly kinetically labile tyrosinated (TYR) MTs which extended from the centrosome and a small population of stable acetylated (ACT) MTs usually (but not exclusively) associated with the centrosome. TYR MTs of undifferentiated cells underwent concentration- and time-dependent disassembly upon exposure to low concentrations of MeHg (1-2 microM), whereas ACT MTs were resistant to MeHg at low concentrations, with many remaining intact even in 5 microM MeHg. After 2 days in retinoic acid the appearance of short neuritic processes was indicative of early differentiation. TYR MTs predominated both in the short neurites and cell soma and remained susceptible to low concentrations of MeHg. ACT MTs also extended into the short neurites but were most often found in small bundles within the perikarya. ACT MTs remained more resistant to MeHg than TYR MTs. The neuron-specific tubulin isotype betaIII was first detected during the second day of differentiation. MTs labeled with antibodies to betaIII s...Continue Reading

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