CREB丝氨酸129位点磷酸化提高miR-132的水平  

Phosphorylation at serine 129 site of CREB for increasing miR-132 level

作　　者：王翔[1] 胡家劭[1] 

机构地区：[1]江汉大学医学院,湖北武汉430056

出　　处：《现代医药卫生》2016年第20期3125-3127,共3页Journal of Modern Medicine & Health

摘　　要：目的通过磷酸化的环磷酸腺苷效应元件结合蛋白(CREB)的激活,使表达记忆的相关蛋白获得长时记忆,探讨CREB丝氨酸(Ser)129位点的磷酸化对微小RNA-132(miR-132)的影响。方法采用长时程增强作用(LTP)电刺激,尾静脉注射方法给予糖原合成酶激酶3β抑制剂SB216763,应用蛋白质印迹法检测大鼠脑内海马区CREB的磷酸化水平,逆转录-聚合酶链反应检测miR-132的表达情况。结果高频刺激CA3-CA1神经环路可成功诱导LTP,使大鼠海马的CREB Ser129位点的磷酸化水平和miR-132的表达明显升高;SB216763可抑制糖原合成酶激酶3β的活性,从而抑制CREB Ser129的磷酸化,使LTP的斜率增幅明显降低,CREB Ser129的磷酸化水平及miR-132的表达明显降低。结论CREB Ser129位点的磷酸化通过调节miR-132的表达促进LTP形成,LTP形成过程中CREB Ser129位点的磷酸化可调节miR-132的表达,从而影响长期记忆形成。Objective To investigate the influence ofphosphorylation at serine（Ser） 129 site of cAMP-response element binging （CREB） protein on micro RNA-132 （miR-132） by activating phosphorylated CREB for the related protein expressing memory obtaining the long term memory. Methods The long-term potentiation（LTP） electric stimulation and tail vein injection were adopted to give glycogen synthase kinase-3β （GSK-3β） inhibitor SB216763, the level of CREB phosphorylation in rat hippocampus area was detected by using the Western blot and the miR-132 expression was detected by using RT-PCR. Results High frequency stimulation at CA3-CA1 neurocircuit could successfully induce LTP, which significantly increased the expres- sion level of phosphorylated CREB Ser 129 in rat hippocampus and miR-132 level;SB216763 could inhibit the GSK-3~ activity, thereby inhibited serine 129 phosphorylation of CREB and significantly decreased the LTP slope amplification and reduced the CREB Ser phosphorylation level and miR-132 expression. Conclusion The phosphorylation of CREB at the serine 129 site could promote the LTP formation by regulating miR-132 expression ,the phosphorylation of CREB Ser 129 site regulates the miR-132 expression during the LTP formation process, thus influences the long term memory formation.

关 键 词：CAMP反应元件结合蛋白质 微RNAs 蛋白质丝氨酸苏氨酸激酶 磷酸转移酶类 糖原合成酶激酶3 长时程增强 电位测定法 记忆 

分 类 号：R345.57[医药卫生—基础医学]