Diazoxon disrupts the expression and distribution of βIII-tubulin and MAP 1B in differentiating N2a cells

Sachana, M, Sidiropoulou, E, Flaskos, J, Harris, W, Robinson, AJ, Woldehiwet, Z and Hargreaves, AJ ORCID: https://orcid.org/0000-0001-9754-5477, 2014. Diazoxon disrupts the expression and distribution of βIII-tubulin and MAP 1B in differentiating N2a cells. Basic & Clinical Pharmacology & Toxicology, 114 (6), pp. 490-496. ISSN 1742-7835

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Abstract

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.

Item Type:	Journal article
Publication Title:	Basic & Clinical Pharmacology & Toxicology
Creators:	Sachana, M., Sidiropoulou, E., Flaskos, J., Harris, W., Robinson, A.J., Woldehiwet, Z. and Hargreaves, A.J.
Publisher:	Wiley
Date:	June 2014
Volume:	114
Number:	6
ISSN:	1742-7835
Identifiers:	Number Type 10.1111/bcpt.12192 DOI
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	26 Apr 2016 10:08
Last Modified:	13 Oct 2017 10:48
URI:	https://irep.ntu.ac.uk/id/eprint/27687

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