Green tea polyphenols potentiate the action of nerve growth factor to induce neuritogenesis: possible role of reactive oxygen species.
Green tea polyphenols potentiate the action of nerve growth factor to induce neuritogenesis: possible role of reactive oxygen species.
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DOI：
10.1002/jnr.22519
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发表时间：
2010-12
影响因子：
4.2
通讯作者：
Gopalakrishna, Rayudu
中科院分区：
文献类型：
--
作者：
Gundimeda, Usha;Mcneill, Thomas H.;Schiffman, Jason E.;Hinton, David R.;Gopalakrishna, Rayudu
外源性神经生长因子（NGF）可以修复受损的轴突，但不能穿过血脑屏障。因此，能够增强内源性NGF的神经突发生能力的药剂在治疗神经损伤中将具有很大的效用。使用PC 12细胞模型，在这里，我们表明，未分级的绿色茶多酚（GTPP）在低浓度（0.1 μg/ml）增强的能力，低浓度的神经生长因子（2 ng/ml）诱导神经突发生的水平与最佳高浓度的神经生长因子（50 ng/ml）单独诱导的水平相当。在我们的实验中，GTPP本身不诱导轴突发生或增加β-微管蛋白III的免疫荧光染色;然而，它增加了神经元标记物neuroadminent-L和GAP-43的mRNA和蛋白质的表达。在GTPP中存在的多酚中，表没食子儿茶素-3-没食子酸酯（EGCG）单独明显增强了NGF诱导的神经突生长。虽然GTPP中存在的其他多酚，特别是表没食子儿茶素和表儿茶素，缺乏这种活性，但它们协同促进了EGCG的这种作用。GTPP还诱导细胞外信号调节激酶（ERK）的激活。ERK通路抑制剂PD 98059阻断GAP-43的表达。TrkA相关酪氨酸激酶抑制剂K252 a部分阻断了这些基因的表达和ERK激活。抗氧化剂，过氧化氢酶（细胞渗透形式）和N-乙酰半胱氨酸（L和D-形式）抑制这些事件，并取消GTPP增强神经生长因子诱导的轴突发生。两者合计，这些结果表明，第一次，GTPP可能通过参与亚致死水平的活性氧增强神经生长因子诱导的轴突发生，并表明，未分级GTPP在这方面比其分级多酚更有效。
Exogenously administered nerve growth factor (NGF) repairs injured axons, but it does not cross the blood-brain barrier. Thus, agents that could potentiate the neuritogenic ability of endogenous NGF would be of great utility in treating neurological injuries. Using the PC12 cell model, here we show that unfractionated green tea polyphenols (GTPP) at low concentrations (0.1 μg/ml) potentiate the ability of low concentrations of NGF (2 ng/ml) to induce neuritogenesis at a level comparable to that induced by optimally high concentrations of NGF (50 ng/ml) alone. In our experiments, GTPP by itself did not induce neuritogenesis or increase immunofluorescent staining for β-tubulin III; however, it increased expression of mRNA and proteins for the neuronal markers neurofilament-L and GAP-43. Among the polyphenols present in GTPP, epigallocatechin-3-gallate (EGCG) alone appreciably potentiated NGF-induced neurite outgrowth. Although other polyphenols present in GTPP, particularly epigallocatechin and epicatechin, lack this activity, they synergistically promoted this action of EGCG. GTPP also induced an activation of extracellular signal-regulated kinases (ERKs). PD98059, an inhibitor of the ERK pathway, blocked the expression of GAP-43. K252a, an inhibitor of TrkA-associated tyrosine kinase, partially blocked the expression of these genes and ERK activation. Antioxidants, catalase (cell-permeable form) and N-acetylcysteine (both L and D-forms) inhibited these events and abolished GTPP potentiation of NGF-induced neuritogenesis. Taken together, these results show for the first time that GTPP potentiates NGF-induced neuritogenesis likely through the involvement of sublethal levels of reactive oxygen species and suggest that unfractionated GTPP is more effective in this respect than its fractionated polyphenols.
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影响因子：
3.5
作者：
Li, P;Yamakuni, T;Ohizumi, Y
通讯作者：
Ohizumi, Y
影响因子：
3.4
作者：
Qi, Jianhua;Han, Chunguang;Ojika, Makoto
通讯作者：
Ojika, Makoto
DOI：
10.1016/j.ijdevneu.2006.09.323
发表时间：
2007-02-01
影响因子：
1.8
作者：
Ina, Atsutoshi;Hayashi, Ken-Ichiro;Kamei, Yuto
通讯作者：
Kamei, Yuto
DOI：
10.1016/j.bbrc.2003.11.178
发表时间：
2004-01-23
影响因子：
3.1
作者：
Hur, JY;Lee, P;Kim, SY
通讯作者：
Kim, SY
DOI：
10.1158/1940-6207.capr-09-0083
发表时间：
2009-06
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Bode AM;Dong Z
通讯作者：
Dong Z