Induction of PC12 cell differentiation by flavonoids is dependent upon extracellular signal-regulated kinase activation

Induction of PC12 cell differentiation by flavonoids is dependent upon extracellular signal-regulated kinase activation
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DOI:
10.1111/j.1471-4159.2004.02563.x
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发表时间:
2004-09-01
影响因子:
4.7
通讯作者:
Maher,P
Maher,P
中科院分区:
医学2区
文献类型:
--
作者:
Sagara,Y;Vanhnasy,J;Maher,P

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许多归因于类黄酮的生理益处被认为源于其有效的抗氧化剂和自由基清除特性。最近,研究表明,黄酮类化合物通过多种机制保护神经细胞免受氧化应激,其中只有一种机制与其抗氧化活性直接相关,这表明特定的黄酮类化合物可能具有其他特性,可以使它们用于治疗导致神经细胞死亡的疾病。特别是,有人问是否有任何类黄酮可以模仿神经营养蛋白。为了检验这种可能性,我们使用PC12细胞观察了类黄酮诱导神经细胞分化的能力。用各种黄酮类化合物处理PC12细胞,以确定它们的神经保护活性与它们的神经突生长促进活性之间是否存在相关性。此外,还检查了类黄酮诱导分化所需的信号通路。我们发现,只有一小部分具有神经保护作用的类黄酮可以通过细胞外信号调节激酶依赖性过程诱导神经突生长。具有神经保护作用的类黄酮的浓度与诱导分化的浓度之间存在很强的相关性。这些结果表明,在病理条件下或正常衰老中,食用特定的黄酮类化合物可以对损伤后的神经细胞产生进一步的有益影响。
Many of the physiological benefits attributed to flavonoids are thought to stem from their potent antioxidant and free radical scavenging properties. Recently, it was shown that flavonoids protect nerve cells from oxidative stress by multiple mechanisms, only one of which is directly related to their antioxidant activity, suggesting that specific flavonoids may have other properties that could make them useful in the treatment of conditions that lead to nerve cell death. In particular, it was asked if any flavonoid could mimic neurotrophic proteins. To examine this possibility, we looked at the ability of flavonoids to induce nerve cell differentiation using PC12 cells. PC12 cells were treated with a variety of flavonoids to determine if there was a correlation between their neuroprotective activity and their neurite outgrowth‐promoting activity. In addition, the signaling pathways required for flavonoid‐induced differentiation were examined. We found that only a small subset of the flavonoids that were neuroprotective could induce neurite outgrowth by an extracellular signal‐regulated kinase‐dependent process. There was a strong correlation between the concentrations of the flavonoids that were neuroprotective and the concentrations that induced differentiation. These results suggest that the consumption of specific flavonoids could have further beneficial effects on nerve cells following injury, in pathological conditions or in normal aging.