蛋白质翻译后修饰调节突触蛋白的稳定性,分类和贩运,并且与情绪障碍有关。然而,调节情绪障碍的分子机制仍未阐明。在这里,我们报道了蛋白质棕榈酰化/亚硝基化串扰在调节大鼠焦虑样行为中的未知作用。根据高架迷宫试验中开臂持续时间的百分比,老鼠被分为高,中等焦虑人群和低焦虑人群。通过酰基-生物素交换试验检测棕榈酰化和亚硝基化水平,我们在高焦虑大鼠的基底外侧杏仁核(BLA)中发现了低棕榈酰化和高亚硝基化水平。此外,我们观察到2-溴棕榈酸酯(2-BP),棕榈酰化抑制剂,诱发焦虑样行为,伴随着BLA中mEPSCs和mIPSCs的振幅和频率降低。此外,我们还发现,在BLA中用7-硝基indazole(7-NI)抑制nNOS活性会引起抗焦虑作用并减少突触传递。有趣的是,地西泮(DZP)迅速提高了BLA中的蛋白质棕榈酰化水平并减弱了蛋白质亚硝基化水平。具体来说,类似于DZP,自愿运行的车轮施加了类似DZP的抗焦虑作用,并在BLA中诱导高棕榈酰化和低亚硝基化水平。最后,用2-BP阻断蛋白棕榈酰化诱导蛋白亚硝基化水平增加,通过7-NI减弱nNOS活性可提高蛋白质棕榈酰化水平。总的来说,这些结果表明,蛋白质棕榈酰化/亚硝基化串扰在协调大鼠焦虑行为中的关键作用,它可以作为抗焦虑干预的潜在目标。
Protein posttranslational modification regulates synaptic protein stability, sorting and trafficking, and is involved in emotional disorders. Yet the molecular mechanisms regulating emotional disorders remain unelucidated. Here we report unknown roles of protein palmitoylation/nitrosylation crosstalk in regulating anxiety-like behaviors in rats. According to the percentages of open arm duration in the elevated plus maze test, the rats were divided into high-, intermediate- and low-anxiety groups. The palmitoylation and nitrosylation levels were detected by acyl-biotin exchange assay, and we found low palmitoylation and high nitrosylation levels in the basolateral amygdala (BLA) of high-anxiety rats. Furthermore, we observed that 2-bromopalmitate (2-BP), a palmitoylation inhibitor, induced anxiety-like behaviors, accompanied with decreased amplitude and frequency of mEPSCs and mIPSCs in the BLA. Additionally, we also found that inhibiting nNOS activity with 7-nitroindazole (7-NI) in the BLA caused anxiolytic effects and reduced the synaptic transmission. Interestingly, diazepam (DZP) rapidly elevated the protein palmitoylation level and attenuated the protein nitrosylation level in the BLA. Specifically, similar to DZP, the voluntary wheel running exerted DZP-like anxiolytic action, and induced high palmitoylation and low nitrosylation levels in the BLA. Lastly, blocking the protein palmitoylation with 2-BP induced an increase in protein nitrosylation level, and attenuating the nNOS activity by 7-NI elevated the protein palmitoylation level. Collectively, these results show a critical role of protein palmitoylation/nitrosylation crosstalk in orchestrating anxiety behavior in rats, and it may serve as a potential target for anxiolytic intervention.