Fibroblast growth factor 2 induces apoptosis in the early primary culture of rat cortical neurons.
Fibroblast growth factor 2 induces apoptosis in the early primary culture of rat cortical neurons.
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DOI：
10.1016/j.yexcr.2010.03.023
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发表时间：
2010-08
影响因子：
3.7
通讯作者：
T. Yagami;K. Takase;Yasuhiro Yamamoto;K. Ueda;N. Takasu;N. Okamura;T. Sakaeda;M. Fujimoto
中科院分区：
文献类型：
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作者：
T. Yagami;K. Takase;Yasuhiro Yamamoto;K. Ueda;N. Takasu;N. Okamura;T. Sakaeda;M. Fujimoto
在中枢神经系统中，已知成纤维细胞生长因子2（FGF 2）在细胞存活和分化中具有重要功能。除了作为神经营养因子的作用外，我们发现FGF 2在皮层神经元的早期原代培养中引起细胞死亡。FGF 2诱导的神经元细胞死亡显示出凋亡特征，例如，染色质凝聚和DNA断裂。FGF 2处理的神经元的超微结构形态表明凋亡特征，如进行性细胞皱缩、质膜起泡、胞质细胞器丢失、染色质聚集和DNA片段化。酪氨酸激酶抑制剂显着拯救神经元从FGF 2诱导的凋亡。FGF 2在细胞凋亡前可明显促进神经元内钙内流。钙离子螯合剂和L型电压敏感性钙通道（L-VSCC）阻断剂均能减弱FGF 2诱导的细胞凋亡，而其他VSCC阻断剂如N型和P/Q型则不能。L-VSCC阻断剂显著抑制FGF 2增强的Ca 2+内流进入神经元。此外，FGF 2还在凋亡前产生活性氧（ROS）。自由基清除剂不仅减少FGF 2产生的ROS，而且减少FGF 2诱导的Ca 2+内流和细胞凋亡。总之，我们证明了在早期神经元培养中，FGF 2通过L-VSCC引起细胞凋亡。
In the central nervous system, fibroblast growth factor 2 (FGF2) is known to have important functions in cell survival and differentiation. In addition to its roles as a neurotrophic factor, we found that FGF2 caused cell death in the early primary culture of cortical neurons. FGF2-induced neuronal cell death showed apoptotic characters, e.g., chromatin condensation and DNA fragmentation. The ultrastructural morphology of FGF2-treated neurons indicated apoptotic features such as progressive cell shrinkage, blebbing of the plasma membrane, loss of cytosolic organelles, clumping of chromatin, and fragmentation of DNA. Tyrosine kinase inhibitors significantly rescued neurons from FGF2-induced apoptosis. FGF2 potentiated a marked influx of Ca2+into neurons before apoptosis. Both a calcium chelator and L-type voltage-sensitive Ca2+channel (L-VSCC) blockers attenuated FGF2-induced apoptosis, whereas other blockers of VSCCs such as N-type and P/Q-types did not. Blockers of L-VSCCs significantly suppressed FGF2-enhanced Ca2+influx into neurons. Moreover, FGF2 also generated reactive oxygen species (ROS) before apoptosis. Radical scavengers reduced not only the FGF2-generated ROS, but also the FGF2-induced Ca2+influx and apoptosis. In conclusion, we demonstrated that FGF2 caused apoptosis via L-VSCCs in the early neuronal culture.