title: Cytisine confers neuronal protection against excitotoxic injury by down-regulating GluN2B-containing NMDA receptors.
abstract: Cytisine (CYT), one of the principal bioactive components derived from the seeds of Cytisus laborinum L, has been widely used for central nervous system (CNS) diseases treatment. The present study investigated the protective effect of CYT on cultured cortical neural injury induced by N-methyl-d-aspartate (NMDA). Our data showed that CYT conferred protective effect against loss of cellular viability induced by brief exposure to 200 μM NMDA in a concentration-dependent manner. CYT significantly inhibited the neuronal apoptosis induced by NMDA exposure by reversing intracellular Ca(2+) overload and balancing Bcl-2 and Bax expression levels. Furthermore, CYT significantly reversed the up-regulation of GluN2B-containing NMDA receptors by exposure to NMDA, but it did not affect the level of GluN2A-containing NMDA receptors. These findings suggest that CYT protects cortical neurons, at least partially, by inhibiting the level of GluN2B-containing NMDA receptors and regulating Bcl-2 family.
authors.affiliation: Department of Pharmacology, School of Pharmacy, The Fourth Military Medical University, Xi'an, Shaanxi Province 710032, PR China.
authors.forename: Yu-Jiao
authors.initials: YJ
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Yang
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Guo
authors.forename: Xu-Bo
authors.initials: XB
authors.lastname: Li
authors.forename: Le
authors.initials: L
authors.lastname: Yang
authors.forename: Ming-Gao
authors.initials: MG
authors.lastname: Zhao
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Wu
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001392:Azocines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005865:Gestational Age; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011807:Quinolizines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D000093843:Quinolizidine Alkaloids
chemical_list: D000470:Alkaloids; D001392:Azocines; D002118:Calcium; D016202:N-Methylaspartate; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D011807:Quinolizines; D016194:Receptors, N-Methyl-D-Aspartate; D051028:bcl-2-Associated X Protein; C494827:Bax protein, mouse; C121001:NR2B NMDA receptor; C052617:Bcl2 protein, mouse; C004712:cytisine; D000093843:Quinolizidine Alkaloids