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Testosterone attenuates morpho-fiunctional alterations by 2-methoxyestradiol exposure and induces differentiation in C6 cells

Manca, Paolo and Chisu, Valentina (2011) Testosterone attenuates morpho-fiunctional alterations by 2-methoxyestradiol exposure and induces differentiation in C6 cells. Journal of Cellular Physiology, Vol. 226 (6), p. 1510-1518. eISSN 1097-4652. Article.

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DOI: 10.1002/jcp.22480

Abstract

2-Methoxyestradiol (2ME) is a cytotoxic drug that interacts with tubulin and alters microtubule dynamics. It has been reported that testosterone (T) has a neuroprotective effect against oxidative stress and induces differentiation in mouse C1300 neuroblastoma cells. Here, we investigated the ability of T to attenuate the cytotoxic effects of 2ME and to induce cell differentiation in an immortalized rat glial cell line, known as C6. C6 cells were exposed for 5 days to 5 µM 2ME, 50 nM T, or both. We evaluated the morphological changes, growth rate, vitality, catalase activity, and glial fibrillary acidic protein (GFAP) immunoreactivity in control and treated C6 cells. Western Blot analyses were used to quantify expression of tyrosinated tubulin (Tyr-Tub), acetylated tubulin (Acet-Tub), total α-tubulin (TOT-Tub), and GFAP. After 2ME exposure, the cells displayed a globular, shrunken shape and retraction or absence of cytoplasmic processes; moreover, 2ME treatment significantly decreased cell growth, cell viability, catalase activity, and expression of both Tyr-Tub and Acet-Tub. However, when T was added, the cells exhibited a glial-like shape, elongated cell processes, and enhanced cell growth, cell vitality, catalase activity, and GFAP immunoreactivity. Densitometric values of Tyr-Tub, Acet-Tub, and GFAP increased significantly when T was present, while Tot-Tub values were unaltered. These results indicate that, in C6 cells, T: i) attenuated the morpho-functional changes caused by 2ME exposure; ii) induced glial differentiation; iii) exerted a direct action on the microtubule system.

Item Type:Article
ID Code:5469
Status:Published
Refereed:Yes
Uncontrolled Keywords:2-Methoxyestradiol, C6 rat glioma, testosterone, cell differentiation, tubulin
Subjects:Area 07 - Scienze agrarie e veterinarie > VET/01 Anatomia degli animali domestici
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > Istituto zooprofilattico sperimentale della Sardegna, Sassari
001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:Wiley-Liss
eISSN:1097-4652
Deposited On:10 Feb 2011 11:22

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