Wang Haijun, Shen Jianying, Xiong Nanxiang, Zhao Hongyang, Chen Yan
Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, People's Republic of China.
Neuroreport. 2011 Oct 26;22(15):733-8. doi: 10.1097/WNR.0b013e32834a58e8.
Nogo-A, a member of the reticulon family, is one of the most important myelin-associated inhibitors for axonal growth, regeneration, and plasticity in the central nervous system. RhoA has been targeted pharmacologically to promote neurite outgrowth and functional recovery in the brain and spinal cord. However, the underlying mechanism of the inhibition of neurite outgrowth by Nogo-A has not yet been fully defined. Protein kinase B (PKB, also known as Akt) is a protein serine/threonine kinase that plays a key role in intracellular signaling and cellular homeostasis. This study reports the role of PKB signaling on Nogo-A-treated PC12 neuronal cells. An inhibitory fragment of Nogo-A (Nogo-66) activated RhoA and reduced the phosphorylation of PKB at Ser473 in a time-dependent manner. In contrast, pretreatment with Y27632, a specific inhibitor of Rho-A, resulted in an increase of the phosphorylation of PKB. Nogo-66 also inhibited the neurite outgrowth of PC12 cells, whereas pretreatment with LY294002, a specific inhibitor of PKB, ameliorated the neurite outgrowth. These data suggest that PKB is involved in the inhibition of neurite outgrowth by Nogo-A in PC12 cells.
Nogo-A是网织蛋白家族的一员，是中枢神经系统中轴突生长、再生和可塑性最重要的髓鞘相关抑制因子之一。RhoA已成为促进脑和脊髓中神经突生长及功能恢复的药理学靶点。然而，Nogo-A抑制神经突生长的潜在机制尚未完全明确。蛋白激酶B（PKB，也称为Akt）是一种蛋白丝氨酸/苏氨酸激酶，在细胞内信号传导和细胞内稳态中起关键作用。本研究报道了PKB信号在Nogo-A处理的PC12神经元细胞中的作用。Nogo-A的一个抑制片段（Nogo-66）以时间依赖性方式激活RhoA并降低Ser473位点的PKB磷酸化水平。相反，用Rho-A特异性抑制剂Y27632预处理会导致PKB磷酸化水平升高。Nogo-66也抑制PC12细胞的神经突生长，而用PKB特异性抑制剂LY294002预处理可改善神经突生长。这些数据表明，PKB参与了Nogo-A对PC12细胞神经突生长的抑制作用。
