Diazoxon Disrupts the Expression and Distribution of βIII-Tubulin and MAP 1B in Differentiating N2a Cells

Autor:	Erasmia Sidiropoulou, Zerai Woldehiwet, John Flaskos, Alan J. Hargreaves, Wayne Harris, Magdalini Sachana, Alex J. Robinson
Rok vydání:	2014
Předmět:	Neurite Metabolite Biology Toxicology Mice Neuroblastoma chemistry.chemical_compound Organophosphorus Compounds Tubulin Microtubule Cell Line Tumor Animals Fluorescent Antibody Technique Indirect Cytoskeleton Pharmacology Cell Differentiation General Medicine N2a cell Molecular biology Isotype chemistry Cell culture biology.protein Neurotoxicity Syndromes Microtubule-Associated Proteins
Zdroj:	Basic & Clinical Pharmacology & Toxicology. 114:490-496
ISSN:	1742-7835
Popis:	This study aimed at assessing the effects of diazoxon (DZO), a major metabolite of the insecticide diazinon (DZ), on key cytoskeletal proteins in differentiating N2a neuroblastoma cells. Initial experiments established that sub-lethal concentrations of 1, 5 and 10 μM DZO produced profound inhibition of neurite outgrowth. Densitometric scanning of probed immunoblots of N2a cell lysates demonstrated that DZO had no effect on total β-tubulin levels. However, probing with a monoclonal antibody that recognised specifically the βIII-tubulin isotype revealed that 10 μM DZO induced a significant reduction in the levels of this particular form. Levels of polyglutamylated tubulin were not altered. Exposure to 10 μM DZO also decreased the expression of microtubule associated protein 1B (MAP 1B). However, DZO had no effect on the expression of MAP tau. DZO also failed to affect the levels neurofilament light (NFL) and neurofilament medium (NFM) chain levels. Indirect immunofluorescence demonstrated that the staining of neurites in treated cells was weaker than in the controls for βIII-tubulin. In conclusion, DZO disrupts the microtubule (MT) network affecting the expression and distribution of two specific MT proteins known to be important in neuritogenesis. DZO may contribute to the developmental neurotoxicity seen following exposure to DZ.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da0c5362a078c0d5663f0cf1c6223ebb https://doi.org/10.1111/bcpt.12192 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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