Rivero Guadalupe, Gabilondo Ane M, García-Sevilla Jesús A, La Harpe Romano, Morentín Benito, Meana J Javier
Department of Pharmacology, University of te Basque Country (UPV/EHU), Leioa, Bizkaia, Spain; BioCruces Health Research Institute and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
Department of Pharmacology, University of te Basque Country (UPV/EHU), Leioa, Bizkaia, Spain; BioCruces Health Research Institute and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
Schizophr Res. 2015 Feb;161(2-3):446-51. doi: 10.1016/j.schres.2014.12.014. Epub 2014 Dec 27.
14-3-3 is a family of conserved regulatory proteins that bind to a multitude of functionally diverse signalling proteins. Various genetic studies and gene expression and proteomic analyses have involved 14-3-3 proteins in schizophrenia (SZ). On the other hand, studies about the status of these proteins in major depressive disorder (MD) are still missing. Immunoreactivity values of cytosolic 14-3-3β and 14-3-3ζ proteins were evaluated by Western blot in prefrontal cortex (PFC) of subjects with schizophrenia (SZ; n=22), subjects with major depressive disorder (MD; n=21) and age-, gender- and postmortem delay-matched control subjects (n=52). The modulation of 14-3-3β and 14-3-3ζ proteins by psychotropic medication was also assessed. The analysis of both proteins in SZ subjects with respect to matched control subjects showed increased 14-3-3β (Δ=33±10%, p<0.05) and 14-3-3ζ (Δ=29±6%, p<0.05) immunoreactivity in antipsychotic-free but not in antipsychotic-treated SZ subjects. Immunoreactivity values of 14-3-3β and 14-3-3ζ were not altered in MD subjects. These results show the specific up-regulation of 14-3-3β and 14-3-3ζ proteins in PFC of SZ subjects and suggest a possible down-regulation of both proteins by antipsychotic treatment.
14-3-3是一类保守的调节蛋白家族，可与多种功能各异的信号蛋白结合。各种遗传学研究以及基因表达和蛋白质组学分析均表明14-3-3蛋白与精神分裂症（SZ）有关。另一方面，关于这些蛋白在重度抑郁症（MD）中的状态的研究仍很缺乏。通过蛋白质印迹法评估了精神分裂症患者（SZ；n=22）、重度抑郁症患者（MD；n=21）以及年龄、性别和死后延迟时间匹配的对照受试者（n=52）前额叶皮质（PFC）中细胞溶质14-3-3β和14-3-3ζ蛋白的免疫反应性值。还评估了精神药物对14-3-3β和14-3-3ζ蛋白的调节作用。与匹配的对照受试者相比，对SZ受试者中这两种蛋白的分析显示，在未接受抗精神病药物治疗的SZ受试者中，14-3-3β（Δ=33±10%，p<0.05）和14-3-3ζ（Δ=29±6%，p<0.05）的免疫反应性增加，而在接受抗精神病药物治疗的SZ受试者中则未增加。MD受试者中14-3-3β和14-3-3ζ的免疫反应性值未改变。这些结果表明SZ受试者PFC中14-3-3β和14-3-3ζ蛋白有特异性上调，并提示抗精神病药物治疗可能会下调这两种蛋白。
