NGF AND BFGF PROTECT RAT HIPPOCAMPAL AND HUMAN CORTICAL-NEURONS AGAINST HYPOGLYCEMIC DAMAGE BY STABILIZING CALCIUM HOMEOSTASIS
NGF AND BFGF PROTECT RAT HIPPOCAMPAL AND HUMAN CORTICAL-NEURONS AGAINST HYPOGLYCEMIC DAMAGE BY STABILIZING CALCIUM HOMEOSTASIS
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DOI：
10.1016/0896-6273(91)90347-3
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发表时间：
1991-12-01
期刊：
影响因子：
16.2
通讯作者：
MATTSON, MP
中科院分区：
文献类型：
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作者：
CHENG, B;MATTSON, MP
神经生长因子和碱性成纤维细胞生长因子最近被证明在中枢神经元中具有生物活性，但其正常功能和作用机制尚不清楚。由于中枢神经元特别容易受到缺血或胰岛素过量引起的低血糖的影响，我们测试了生长因子可以保护神经元免受低血糖损伤的假设。在培养的人大脑皮层和大鼠海马细胞中，神经生长因子和碱性成纤维细胞生长因子均可预防缺糖所致的神经元损伤(表皮生长因子无效)。当在低血糖发生前(NGF和bFGF)或在NGF开始低血糖后12小时内给予生长因子时，提供了保护。细胞内钙水平的直接测量和钙内流的调节表明，细胞内钙水平的持续升高介导了低血糖损伤。神经生长因子和碱性成纤维细胞生长因子均可抑制低血糖引起的细胞内钙升高。这些发现表明，生长因子可以稳定中枢神经元的钙稳态，从而保护它们免受环境伤害。
NGF and bFGF have recently been shown to have biological activity in central neurons, but their normal functions and mechanisms of action are unknown. Since central neurons are particularly vulnerable to hypoglycemia that occurs with ischemia or insulin overdose, we tested the hypothesis that growth factors can protect neurons against hypoglycemic damage. NGF and bFGF each prevented glucose deprivation-induced neuronal damage in human cerebral cortical and rat hippocampal cell cultures (EGF was ineffective). Protection was afforded when the growth factors were administered before (NGF and bFGF) or up to 12 hr following (NGF) the onset of hypoglycemia. Direct measurements of intracellular calcium levels and manipulations of calcium influx demonstrated that sustained elevations in intracellular calcium levels mediated the hypoglycemic damage. NGF and bFGF each prevented the hypoglycemia-induced elevations of intracellular calcium. These findings indicate that growth factors can stabilize neuronal calcium homeostasis in central neurons and thereby protect them against environmental insults.