Effects of geldanamycin on neurite outgrowth-related proteins and kinases in nerve growth factor-differentiated pheochromocytoma 12 cells
Effects of geldanamycin on neurite outgrowth-related proteins and kinases in nerve growth factor-differentiated pheochromocytoma 12 cells
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格尔德霉素对神经生长因子分化的嗜铬细胞瘤12细胞中神经突生长相关蛋白和激酶的影响
DOI：
10.1016/j.jphs.2019.07.011
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发表时间：
2019
期刊：
影响因子：
3.5
通讯作者：
Hara S
中科院分区：
文献类型：
--
作者：
Migita K;Matsumoto T;Terada K;Ono K;Hara S
热休克蛋白90 （HSP90）拮抗剂目前正被评价为潜在的抗癌药物。然而，与这些药物相关的副作用，如疲劳和疼痛，表明它们会影响神经元。因此，为了了解HSP90抑制剂对神经元的影响，我们研究了HSP90拮抗剂格尔达霉素对神经生长因子（NGF）分化的嗜铬细胞瘤12 （PC12）细胞的影响，特别是对NGF通路中蛋白质和激酶的表达和磷酸化的影响。格尔达霉素显著抑制ngf诱导的PC12细胞神经突生长和Akt和细胞外信号相关激酶1/2的磷酸化。此外，在NGF存在的情况下，格尔达霉素抑制了塌陷素反应介质蛋白2的磷酸化和周期蛋白依赖性激酶5的表达，但对糖原合成酶激酶3β的表达没有显著影响。这些结果表明，格尔达霉素影响与神经突生长有关的微管结合蛋白和激酶，从而诱导神经元损伤。
Heat shock protein 90 (HSP90) antagonists are currently being evaluated as potential anticancer drugs. However, adverse effects related to these drugs, such as fatigue and pain, suggest that they affect neurons. Therefore, to understand the influence of HSP90 inhibitors on neurons, we investigated the effects of geldanamycin, an HSP90 antagonist, on nerve growth factor (NGF)-differentiated pheochromocytoma 12 (PC12) cells, particularly, on the expression and phosphorylation of proteins and kinases in the NGF pathway. Geldanamycin significantly inhibited NGF-induced neurite outgrowth and phosphorylation of Akt and extracellular signal-related kinase 1/2 in PC12 cells. Furthermore, geldanamycin inhibited the phosphorylation of collapsin response mediator protein 2 and the expression of cyclin-dependent kinase 5 in the presence of NGF, but did not significantly affect the expression of glycogen synthase kinase 3β. These results suggest that geldanamycin influences microtubule-binding proteins and kinases relating to neurite outgrowth, thereby inducing neuronal impairment.