Yang Yoo Jung, Lee Hak Ju, Choi Don Ha, Huang Hai Shan, Lim Sung Cil, Lee Myung Koo
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, Republic of Korea.
Neurosci Lett. 2008 Jul 25;440(1):14-8. doi: 10.1016/j.neulet.2008.05.051. Epub 2008 May 18.
The neurite outgrowth-promoting effects of scoparone isolated from the stem bark of Liriodendron tulipifera were investigated in PC12 cells. At a concentration of 200 microM, scoparone markedly induced neurite outgrowth from PC12 cells. Scoparone at 200 microM also enhanced the outgrowth of neurites from cells in the presence of nerve growth factor (NGF, 2 ng/ml). The levels of intracellular cyclic AMP and concentration of Ca2+ were also increased by 200 microM scoparone. In addition, scoparone at 200 microM increased the activities of extracellular signal-regulated protein kinase (ERK), cyclic AMP-dependent protein kinase (PKA), protein kinase C (PKC) and Ca2+/calmodulin kinase II (CaMK II). However, scoparone-induced neurite outgrowth was blocked by a mitogen-activated protein kinase inhibitor (U0126), a PKA inhibitor (H89), a PKC inhibitor (GF109203X) and a CaMK II inhibitor (KN62). These kinase inhibitors also reduced the scoparone-induced neurite outgrowth associated with NGF. These results suggest that scoparone can induce neurite outgrowth by stimulating the upstream steps of ERK, PKA, PKC and CaMK II in PC12 cells.
研究了从北美鹅掌楸茎皮中分离出的滨蒿内酯对PC12细胞神经突生长的促进作用。在200微摩尔浓度下，滨蒿内酯显著诱导PC12细胞的神经突生长。200微摩尔的滨蒿内酯在存在神经生长因子（NGF，2纳克/毫升）的情况下也增强了细胞神经突的生长。200微摩尔的滨蒿内酯还使细胞内环磷酸腺苷水平和钙离子浓度升高。此外，200微摩尔的滨蒿内酯增加了细胞外信号调节蛋白激酶（ERK）、环磷酸腺苷依赖性蛋白激酶（PKA）、蛋白激酶C（PKC）和钙/钙调蛋白依赖性蛋白激酶II（CaMK II）的活性。然而，滨蒿内酯诱导的神经突生长被丝裂原活化蛋白激酶抑制剂（U0126）、PKA抑制剂（H89）、PKC抑制剂（GF109203X）和CaMK II抑制剂（KN62）阻断。这些激酶抑制剂也减少了与NGF相关的滨蒿内酯诱导的神经突生长。这些结果表明，滨蒿内酯可通过刺激PC12细胞中ERK、PKA、PKC和CaMK II的上游步骤来诱导神经突生长。
