Trollér U, Zeidman R, Svensson K, Larsson C
Lund University, Molecular Medicine, Malmö University Hospital, 205 02 Malmö, Sweden
FEBS Lett. 2001 Nov 9;508(1):126-30. doi: 10.1016/s0014-5793(01)03043-5.
Protein kinase C (PKC) activation induces neuronal differentiation of SH-SY5Y neuroblastoma cells. This study examines the role of PKCbeta isoforms in this process. The PKCbeta-specific inhibitor LY379196 had no effect on 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced neurite outgrowth from SH-SY5Y neuroblastoma cells. On the other hand, PKCbeta inhibition suppressed the TPA-stimulated increase in neuropeptide Y mRNA, activation of neuropeptide Y gene promoter elements, and phosphorylation of Erk1/2. The TPA-induced increase in neuropeptide Y expression was also inhibited by the MEK inhibitor PD98059. These data indicate that activation of a PKCbeta isoform, through a pathway involving Erk1/2, leads to increased expression of neuronal differentiation genes in neuroblastoma cells.
蛋白激酶C（PKC）激活可诱导SH-SY5Y神经母细胞瘤细胞发生神经元分化。本研究探讨了PKCβ亚型在此过程中的作用。PKCβ特异性抑制剂LY379196对12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的SH-SY5Y神经母细胞瘤细胞神经突生长没有影响。另一方面，PKCβ抑制可抑制TPA刺激的神经肽Y mRNA增加、神经肽Y基因启动子元件的激活以及Erk1/2的磷酸化。MEK抑制剂PD98059也抑制了TPA诱导的神经肽Y表达增加。这些数据表明，通过涉及Erk1/2的途径激活PKCβ亚型会导致神经母细胞瘤细胞中神经元分化基因的表达增加。
