The previous study indicated that DHCR24/seladin-1 was an important neuroprotective effector. However, the molecular mechanisms that androgen modulates the expression of seladin-1 remain incompletely defined. In this paper, we showed that the expression of seladin-1 was significantly increased by testosterone at all concentrations tested at the protein and mRNA levels in CO cells, the selective AR antagonist flutamide obviously inhibited the effect in a concentration-dependent manner. Furthermore, we found that testosterone significantly increased the phosphorylation level of V-akt murine thymoma viral oncogene (Akt), a key effector of the phosphoinositide 3-kinase (P13-K)/Akt signaling pathway, while a specific P13-K inhibitor LY294002 obviously prevented the activation of Akt phosphorylation. In addition, the P13-K inhibitor LY294002 also markedly blocked the up-regulation expression of seladin-1 gene induced by testosterone at the protein and mRNA levels. Collectively, the above results suggested that testosterone regulated the expression of seladin-1 by the intracellular androgen receptor (iAR)-mediated genomic signaling pathway and the non-genomic Pi3-K/Akt signaling pathway in C6 glial cells. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
[1]Fudan Univ, Dept Neurol, Jinshan Hosp, Shanghai 200540, Peoples R China.
[2]Fudan Univ, Minist Educ, Key Lab Mol Med, Shanghai 200032, Peoples R China.
[3]Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai 200040, Peoples R China.
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