Maher Pamela
The Salk Institute for Biological Studies, Cellular Neurobiology, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Arch Biochem Biophys. 2008 Aug 15;476(2):139-44. doi: 10.1016/j.abb.2008.03.023. Epub 2008 Mar 26.
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 24h 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.
为了探究特定类黄酮能否替代神经营养因子的可能性，我们检测了黄酮醇漆黄素和几种相关类黄酮支持低密度、无血清培养的大鼠皮质神经元存活的能力。通常情况下，这些细胞在没有营养因子时会在24小时内死亡，但在漆黄素和几种相关类黄酮存在的情况下，细胞能够存活并长出长神经突。虽然几种与漆黄素相关的类黄酮的促存活作用部分依赖于ERK激活，但漆黄素的作用并非如此。漆黄素可增强谷胱甘肽的合成，但漆黄素的促存活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了漆黄素促进存活的能力。与这一观察结果一致，漆黄素增加了蛋白酶体活性。这些结果共同证明了漆黄素的一种新活性，并将这种活性与其神经营养作用联系起来。
