Reduced tubulin tyrosination as an early marker of mercury toxicity in differentiating N2a cells.
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.
Lawton
M
M
Interdisciplinary Biomedical Research Centre, School of Biomedical and Natural Sciences, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS, United Kingdom.
Iqbal
M
M
Kontovraki
M
M
Lloyd Mills
C
C
Hargreaves
A J
AJ
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*
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D008767:Methylmercury Compounds; D008868:Microtubule Proteins; D014404:Tubulin; D013849:Thimerosal; D014443:Tyrosine; C004925:methylmercuric chloride