Activation of phosphatidylinositol 3‐kinase by brain‐derived neurotrophic factor gene transfection in septo‐hippocampal cultures

Brain‐derived neurotrophic factor (BDNF) has therapeutic potential for treatment of the injured central nervous system. BDNF induces both differentiation and survival of neurons by binding to trkB receptors. This interaction stimulates the intrinsic tyrosine kinase activity of trkB, initiating a signal cascade involving the phosphorylation of intracellular protein on tyrosine, serine, and threonine residues. The purpose of this investigation was to examine the effects of cationic lipid‐mediated gene transfection of BDNF on phosphatidylinositol 3 (PI3)‐kinase activity in primary septo‐hippocampal cell cultures. Thirty‐six hours after BDNF gene transfection in the primary CNS cell culture, PI3‐kinase activity was significantly increased. The increased PI3‐kinase activity was inhibited by wortmannin, a selective and irreversible inhibitor of PI3‐kinase. In addition, wortmannin blocked neurofilament increases induced by BDNF gene transfection. This result suggests a possible role of PI3‐kinase activation in neuroprotective effects produced by BDNF gene transfection. J. Neurosci. Res. 52:192–200, 1998. © 1998 Wiley‐Liss, Inc.

脑源性神经营养因子（BDNF）对治疗受损的中枢神经系统具有治疗潜力。BDNF通过与TrkB受体结合，诱导神经元的分化和存活。这种相互作用刺激TrkB固有的酪氨酸激酶活性，启动一个涉及细胞内蛋白质的酪氨酸、丝氨酸和苏氨酸残基磷酸化的信号级联反应。本研究的目的是检测阳离子脂质介导的BDNF基因转染对原代隔海马细胞培养物中磷脂酰肌醇3（PI3）激酶活性的影响。在原代中枢神经系统细胞培养物中进行BDNF基因转染36小时后，PI3激酶活性显著增加。这种增加的PI3激酶活性被渥曼青霉素（一种选择性且不可逆的PI3激酶抑制剂）所抑制。此外，渥曼青霉素阻断了由BDNF基因转染诱导的神经丝增加。这一结果表明PI3激酶激活在BDNF基因转染产生的神经保护作用中可能起作用。《神经科学研究杂志》1998年第52卷第192 - 200页。© 1998威利 - 利斯公司