Sheng Hui, Sun Tingting, Cong Binhai, He Ping, Zhang Yanmin, Yan Jin, Lu Changlin, Ni Xin
Departments of Physiology, Second Military Medical University, Shanghai, China.
Am J Physiol Endocrinol Metab. 2008 Oct;295(4):E938-46. doi: 10.1152/ajpendo.90462.2008. Epub 2008 Aug 19.
Corticotropin-releasing hormone (CRH) has been shown to exhibit various functions in hippocampus. In the present study, we examined the effect of CRH on the expression of serum/glucocorticoid-inducible protein kinase-1 (SGK-1), a novel protein kinase, in primary cultured hippocampal neurons. A dose-dependent increase in mRNA and protein levels of SGK-1 as well as frequency of SGK-1-positive neurons occurred upon exposure to CRH (1 pmol/l to 10 nmol/l). These effects can be reversed by the specific CRH-R1 antagonist antalarmin but not by the CRH-R2 antagonist astressin 2B. Blocking adenylate cyclase (AC) activity with SQ22536 and PKA with H89 completely prevented CRH-induced mRNA and protein expression of SGK-1. Blockage of PLC or PKC did not block CRH-induced SGK-1 expression. Our results suggest that CRH act on CRH-R1 to stimulate SGK-1 mRNA and protein expression in cultured hippocampal neurons via a mechanism that is involved in AC/PKA signaling pathways.
促肾上腺皮质激素释放激素(CRH)已被证明在海马体中具有多种功能。在本研究中,我们检测了CRH对原代培养海马神经元中血清/糖皮质激素诱导蛋白激酶-1(SGK-1,一种新型蛋白激酶)表达的影响。暴露于CRH(1皮摩尔/升至10纳摩尔/升)后,SGK-1的mRNA和蛋白水平以及SGK-1阳性神经元的频率呈剂量依赖性增加。这些效应可被特异性CRH-R1拮抗剂安他乐明逆转,但不能被CRH-R2拮抗剂阿施力辛2B逆转。用SQ22536阻断腺苷酸环化酶(AC)活性以及用H89阻断蛋白激酶A(PKA)活性可完全阻止CRH诱导的SGK-1的mRNA和蛋白表达。阻断磷脂酶C(PLC)或蛋白激酶C(PKC)并不能阻断CRH诱导的SGK-1表达。我们的结果表明,CRH通过作用于CRH-R1,经由涉及AC/PKA信号通路的机制,刺激培养海马神经元中SGK-1的mRNA和蛋白表达。