Department of Physiology and The Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai 200433, PR China.
Neuropeptides. 2012 Apr;46(2):93-8. doi: 10.1016/j.npep.2011.12.004. Epub 2012 Jan 14.
Corticotropin-releasing hormone (CRH) family peptides as well as their receptors have been shown to exhibit various functions in hippocampus. However, effects of CRH receptors activation on collapsin response mediator protein 3 (CRMP3), the key protein for dendrite outgrowth and cell apoptosis, remain unclear. In the present study, we determined the effects of CRHR1 and CRHR2 on CRMP3 expression in cultured hippocampal neurons. CRH and urocortin II (UCNII) dose-dependently suppressed CRMP3 mRNA and protein expression. The inhibitory effect on CRMP3 expression was completely reversed by CRHR2 antagonist but not by CRHR1 antagonist. Investigations on the signaling pathways of UCNII showed that CRHR2 mediated UCNII-induced increase in phosphorylated phospholipase C (PLC)-β3 expression. Blocking PLC activity with U73122 and PKC with Gö6976 completely prevented UCNII-inhibited CRMP3 expression. Our results suggest that CRHR2 activation decrease CRMP3 expression in hippocampal neurons via a mechanism that is dependent on PLC/PKC signaling pathways.
促肾上腺皮质释放激素（CRH）家族肽及其受体在海马体中表现出多种功能。然而，CRH 受体激活对树突生长和细胞凋亡的关键蛋白 collapsin 反应介质蛋白 3（CRMP3）的影响尚不清楚。在本研究中，我们确定了 CRHR1 和 CRHR2 对培养的海马神经元中 CRMP3 表达的影响。CRH 和孤啡肽 II（UCNII）剂量依赖性地抑制 CRMP3 mRNA 和蛋白表达。CRHR2 拮抗剂完全逆转了对 CRMP3 表达的抑制作用，但 CRHR1 拮抗剂则没有。对 UCNII 信号通路的研究表明，CRHR2 介导 UCNII 诱导的磷酸化磷脂酶 C（PLC）-β3 表达增加。用 U73122 和 PKC 抑制剂 Gö6976 阻断 PLC 活性可完全阻止 UCNII 抑制 CRMP3 表达。我们的结果表明，CRHR2 激活通过依赖于 PLC/PKC 信号通路的机制降低海马神经元中 CRMP3 的表达。
