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Chisu, V., Lepore, M. G., Zedda, M. & Farina, V. Testosterone induces neuroprotection from oxidative stress. Effects on catalase activity and 3-Nitro-L-styrosine incorporation into -tubulin in a mouse neuroblastoma cell line. Arch. Ital. Biol. 144, 63-73

Department of Animal Biology, University of Sassari.
Archives italiennes de biologie (Impact Factor: 1.49). 06/2006; 144(2):63-73. DOI: 10.4449/aib.v144i2.882
Source: PubMed

ABSTRACT

3-nitro-L-tyrosine is formed by nitric oxide following different pathways such as NADPH oxidase, xanthine oxidase or glutamate NMDA receptor activation and is involved in the pathology of different neurological disorders. Unlike estradiol, a neuroprotective role of androgens against oxidative cell injury has not been fully investigated. This work targets the possible effects of testosterone on neuroblastoma cells exposed to 3-nitro-L-tyrosine. C1300 mouse undifferentiated neuroblastoma cells exposed to 3-nitro-L-tyrosine were cultured in the presence of testosterone. Morphological examination, proliferation and nuclear viability assays were performed. The expression of tyrosinated alpha-tubulin and incorporation of 3-nitro-L-tyrosine into protein were also estimated. Cells exposed to 3-nitro-L-tyrosine showed globular shape, reduced cytoplasmic processes and growth inhibition in comparison with controls. When testosterone was added to the medium, these changes were not evident. In addition, testosterone induced an upregulation of tyrosinated alpha-tubulin, a marker of neuronal plasticity, and a decrease in 3-nitro-L-tyrosine incorporation into tubulin. Our results suggest that testosterone exposure can diminish 3-nitro-L-tyrosine toxic effects on the morphology and growth rate of neuroblastoma cells. The upregulation of tyrosinated alpha-tubulin in testosterone-exposed cells would be consistent with concurrent plasticity events. Failure in alpha-tubulin nitration detected in cells exposed to both 3-nitro-L-tyrosine and testosterone, may support the idea that testosterone interferes with 3-nitro-L-tyrosine protein incorporation. Moreover, testosterone-induced neuroprotection likely entails a linkage with the androgen receptor as is suggested by the flutamide-induced inhibition of the hormone activity. Finally, the neuroprotective effects of testosterone in neuroblastoma cells could deal with the cellular antioxidant defence system, as shown by testosterone-induced increase in catalase activity.

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Available from: Valentina Chisu
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    • "A different effect was demonstrated for the oxidative stress – induced neuronal injury: direct antioxidant mechanism may be not involved in neuroprotection induced by androgens since micromolar concentrations of testosterone have no protective effects against cell death induced by the oxidative stressors [189]. However, other Authors previously reported conflicting results as they showed that in neuroblastoma cells, neuroprotective effects of testosterone could deal with the cellular antioxidant defense system [190] [191]. Other studies support a neuroprotective role for androgens, in which androgens can protect against oxidative stress damage [192] [193]. "
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    • "After administration of TES or MP, CAT levels increased significantly revealing the antioxidant activity of both drugs. Also, previous studies demonstrated the antioxidant activity of TES [10] [19] [54] [57]. Furthermore, XO is another important source of reactive oxygen species [58]. "
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    • "However, evidence for a causal relationship between T release and cognitive functioning is still missing. Such an association might be assumed as T has shown to have a neuroprotective role in the central nervous system (reviewed by Bialek, Zaremba, Borowicz, & Czuczwar, 2004; Chisu et al., 2006). T receptors have been found in cortex regions and the hippocampus (e.g., Beyenburg et al., 2000; Goldstein et al., 2001). "
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