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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Basic fibroblast growth factor: Lysine 134 is essential for its neuroprotective activity.
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Basic fibroblast growth factor: Lysine 134 is essential for its neuroprotective activity.

机译：碱性成纤维细胞生长因子：赖氨酸134对其神经保护活性至关重要。

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摘要

Basic fibroblast growth factor (bFGF) is a heparin-binding growth factor known to cause cell proliferation, angiogenesis and neuroprotection. We have performed site-directed mutagenesis to identify the amino acids that are essential for heparin/growth factor interaction and for neuroprotection. Binding to heparin-acrylic beads was markedly reduced when lysine in position 134 of bFGF was replaced by alanine. Wildtype (wt)-bFGF was shown to protect rat primary cultures of embryonic hippocampal neurons against damage caused by staurosporine and to reduce the infarct size in mice after focal cerebral ischemia. These neuroprotective effects of wt-bFGF could not be shown for the mutant bFGF(K134A). Furthermore, phosphorylation of Akt and ERK1/2 was significantly reduced in cultured neurons treated with bFGF(K134A) indicating diminished intracellular signaling compared to neurons treated with wt-bFGF. In conclusion, lysine at position 134 of bFGF is essential for bFGF to bind heparin, then to interact with its receptor and, subsequently, to protect neurons against damage.
机译：碱性成纤维细胞生长因子（bFGF）是肝素结合生长因子，已知会导致细胞增殖，血管生成和神经保护。我们已经进行了定点诱变，以鉴定对于肝素/生长因子相互作用和神经保护至关重要的氨基酸。当bFGF 134位的赖氨酸被丙氨酸替代时，与肝素-丙烯酸珠的结合显着降低。已显示野生型（wt）-bFGF可保护大鼠海马神经元原代培养物免受星形孢菌素引起的损害，并减少局灶性脑缺血后小鼠的梗塞面积。 wt-bFGF的这些神经保护作用未显示出突变bFGF（K134A）。此外，与用wt-bFGF处理的神经元相比，在用bFGF（K134A）处理的培养神经元中Akt和ERK1 / 2的磷酸化显着降低。总之，bFGF 134位的赖氨酸对于bFGF结合肝素，然后与其受体相互作用并随后保护神经元免受损害至关重要。

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