title: Reduced tubulin tyrosination as an early marker of mercury toxicity in differentiating N2a cells.
abstract: The aims of this work were to compare the effects of methyl mercury chloride and thimerosal on neurite/process outgrowth and microtubule proteins in differentiating mouse N2a neuroblastoma and rat C6 glioma cells. Exposure for 4h to sublethal concentrations of both compounds inhibited neurite outgrowth to a similar extent in both cells lines compared to controls. In the case of N2a cells, this inhibitory effect by both compounds was associated with a fall in the reactivity of western blots of cell extracts with monoclonal antibody T1A2, which recognises C-terminally tyrosinated alpha-tubulin. By contrast, reactivity with monoclonal antibody B512 (which recognises total alpha-tubulin) was unaffected at the same time point. These findings suggest that decreased tubulin tyrosination represents a neuron-specific early marker of mercury toxicity associated with impaired neurite outgrowth.
authors.affiliation: Interdisciplinary Biomedical Research Centre, School of Biomedical and Natural Sciences, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, United Kingdom.
authors.forename: M
authors.initials: M
authors.lastname: Lawton
authors.forename: M
authors.initials: M
authors.lastname: Iqbal
authors.forename: M
authors.initials: M
authors.lastname: Kontovraki
authors.forename: C
authors.initials: C
authors.lastname: Lloyd Mills
authors.forename: A J
authors.initials: AJ
authors.lastname: Hargreaves
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015415:Biomarkers; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D005910:Glioma / Q000378:metabolism; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008868:Microtubule Proteins / Q000187:drug effects / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D051381:Rats; D013849:Thimerosal / Q000633:toxicity*; D014404:Tubulin / Q000187:drug effects* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D008767:Methylmercury Compounds; D008868:Microtubule Proteins; D014404:Tubulin; D013849:Thimerosal; D014443:Tyrosine; C004925:methylmercuric chloride