title: Stepholidine protects against H2O2 neurotoxicity in rat cortical neurons by activation of Akt.
abstract: The fundamental pathological process(es) associated with schizophrenia (SZ) remain(s) uncertain, but multiple lines of evidence suggest that this condition is associated with excessive stimulation of striatal dopamine (DA) D2 receptors, deficient stimulation of medial prefrontal cortex (mPFC) D1 receptors as well as neuronal apoptosis. Unlike typical antipsychotics, stepholidine (SPD), which is isolated from the Chinese herb stephania, has D1 and D2 dual properties and regulates neuronal cell differentiation and proliferation. It is unknown, however, whether it possesses a neuroprotective property. Here, we report that SPD prevented neuronal cell death from H2O2 exposure and increased the levels of phosphorylated Akt (pAkt), a serine/threonine protein kinase. The SPD-induced neuroprotection and activation of Akt were blocked by LY294002, a PI3-K inhibitor, suggesting that the anti-apoptotic action of SPD is mediated via the PI3-K/Akt signaling pathway. Thus, as a survival or anti-apoptotic factor for neuronal cells, SPD may contribute to the therapeutic action of SPD in SZ treatment.
authors.affiliation: Department of Psychiatry, USUHS, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. lezhang@usuhs.mil
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Rulun
authors.initials: R
authors.lastname: Zhou
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Xiang
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000166:cytology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism* / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D013997:Time Factors
chemical_list: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001599:Berberine; D002867:Chromones; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D006220:Haloperidol; D006861:Hydrogen Peroxide; D009025:Morpholines; D018696:Neuroprotective Agents; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C010513:stepholidine; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C044846:SKF83566; C494920:Akt1 protein, rat