Byts Nadiya, Samoylenko Anatoly, Woldt Helge, Ehrenreich Hannelore, Sirén Anna-Leena
Division of Clinical Neuroscience, Max-Planck-Institute of Experimental Medicine, Hermann-Rein-Str. 3, Göttingen, D-37075, Germany.
Neurochem Res. 2006 Oct;31(10):1219-30. doi: 10.1007/s11064-006-9149-0. Epub 2006 Oct 5.
Correct timing and spatial location of growth factor expression is critical for undisturbed brain development and functioning. In terminally differentiated cells distinct biological responses to growth factors may depend on cell type specific activation of signalling cascades. We show that the hematopoietic growth factors thrombopoietin (TPO) and granulocyte colony-stimulating factor (GCSF) exert cell type specific effects on survival, proliferation and the degree of phosphorylation of Akt1, ERK1/2 and STAT3 in rat hippocampal neurons and cortical astrocytes. In neurons, TPO induced cell death and selectively activated ERK1/2. GCSF protected neurons from TPO- and hypoxia-induced cell death via selective activation of Akt1. In astrocytes, neither TPO nor GCSF had any effect on cell viability but inhibited proliferation. This effect was accompanied by activation of ERK1/2 and inhibition of STAT3 activity. A balance between growth factors, their receptors and signalling proteins may play an important role in regulation of neural cell survival.
生长因子表达的正确时间和空间定位对于大脑的正常发育和功能至关重要。在终末分化细胞中，对生长因子的不同生物学反应可能取决于信号级联的细胞类型特异性激活。我们发现，造血生长因子血小板生成素（TPO）和粒细胞集落刺激因子（GCSF）对大鼠海马神经元和皮质星形胶质细胞的存活、增殖以及Akt1、ERK1/2和STAT3的磷酸化程度具有细胞类型特异性影响。在神经元中，TPO诱导细胞死亡并选择性激活ERK1/2。GCSF通过选择性激活Akt1保护神经元免受TPO和缺氧诱导的细胞死亡。在星形胶质细胞中，TPO和GCSF对细胞活力均无影响，但抑制增殖。这种作用伴随着ERK1/2的激活和STAT3活性的抑制。生长因子、其受体和信号蛋白之间的平衡可能在神经细胞存活的调节中起重要作用。
