Testosterone up-regulates seladin-1 expression by iAR and PI3-K/Akt signaling pathway in C6 cells

sThe 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 C6 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 (PI3-K)/Akt signaling pathway, while a specific PI3-K inhibitor LY294002 obviously prevented the activation of Akt phosphorylation. In addition, the PI3-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.

► Testosterone significantly promotes activation of Akt phosphorylation in C6 cells. ► Testosterone up-regulates the expression of seladin-1 via the AR-mediated genomic pathway. ► Testosterone up-regulates the expression of seladin-1 via the PI3-K/Akt pathway.