The flavonoid fisetin promotes nerve cell survival from trophic factor withdrawal by enhancement of proteasome activity
The flavonoid fisetin promotes nerve cell survival from trophic factor withdrawal by enhancement of proteasome activity
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DOI：
10.1016/j.abb.2008.03.023
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发表时间：
2008-08-15
影响因子：
3.9
通讯作者：
Maher, Pamela
中科院分区：
文献类型：
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作者：
Maher, Pamela
为了探索特定的黄酮类化合物可以替代神经营养因子的可能性，我们研究了黄酮醇非瑟酮和几种相关的黄酮类化合物支持大鼠皮层神经元低密度无血清培养物存活的能力。正常情况下，这些细胞在缺乏营养因子的情况下在24小时内死亡，但在非瑟酮和几种相关的类黄酮的存在下，细胞存活并产生长的神经突。虽然几种非瑟酮相关类黄酮的生存促进作用部分依赖于ERK激活，但非瑟酮的作用并非如此。非瑟酮可以促进谷胱甘肽的合成，但非瑟酮的促生存作用也不依赖于谷胱甘肽。然而，蛋白酶体抑制剂几乎完全阻断非瑟酮促进存活的能力。与此观察结果一致，非瑟酮增加蛋白酶体活性。总之，这些结果证明了非瑟酮的一种新活性，并将这种活性与其神经营养作用联系起来。(C)2008年爱思唯尔公司All rights reserved.
To explore the possibility that specific flavonoids can substitute for neurotrophic factors, we examined the ability of the flavonol fisetin and several related flavonoids to support the survival of low density, serum-free cultures of rat cortical neurons. Normally these cells die within 24 h in the absence of trophic factors but in the presence of fisetin and several related flavonoids the cells survive and produce long neurites. While the survival-promoting effect of several of the fisetin-related flavonoids was partially dependent on ERK activation, the effect of fisetin was not. Fisetin can enhance glutathione synthesis but the survival-promoting effect of fisetin was also not dependent on glutathione. However, proteasome inhibitors almost completely blocked the ability of fisetin to promote Survival, Consistent with this observation, fisetin increased proteasome activity. Together these results demonstrate a new activity for fisetin and tie this activity to its neurotrophic effects. (C) 2008 Elsevier Inc. All rights reserved.