title: Testosterone up-regulates seladin-1 expression by iAR and PI3-K/Akt signaling pathway in C6 cells.
abstract: 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 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.
authors.affiliation: Department of Neurology, Jinshan Hospital Affiliated to Fudan University, Shanghai 200540, China. hbzyy@hotmail.com
authors.forename: Hengbing
authors.initials: H
authors.lastname: Zu
authors.forename: Junfeng
authors.initials: J
authors.lastname: Wu
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Hong
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013739:Testosterone / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D009419:Nerve Tissue Proteins; D044925:Oxidoreductases Acting on CH-CH Group Donors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011944:Receptors, Androgen; D013739:Testosterone; C000600134:DHCR24 protein, rat