Scapagnini Giovanni, Butterfield D Allan, Colombrita Claudia, Sultana Rukhsana, Pascale Alessia, Calabrese Vittorio
Institute of Neurological Sciences, CNR, 95123 Catania, Italy.
Antioxid Redox Signal. 2004 Oct;6(5):811-8. doi: 10.1089/ars.2004.6.811.
In the CNS, the heme oxygenase (HO) system has been reported to be active and to operate as a fundamental defensive mechanism for neurons exposed to an oxidant challenge. We have recently shown that both curcumin and caffeic acid phenethyl ester, two phenolic natural compounds, potently induce HO-1 expression and activity in rat astrocytes. We have extended our previous findings examining the effects of two other plant-derived phenolic compounds, with analogous chemical structures, in rat astrocytes and neurons. Ethyl ferulate (ethyl 4-hydroxy-3-methoxycinnamate) (EFE), the naturally occurring ester of ferulic acid, was able to induce HO-1 protein expression. Maximal expression of HO-1 mRNA and protein and a significant increase in HO activity were detected after 6 h of incubation with 15 microM EFE in astrocytes and 5 microM EFE in neurons. Higher concentrations of EFE (50 microM) caused a substantial cytotoxic effect with no change in HO-1 protein expression and activity. Exposure of astrocytes to resveratrol, a phytoalexin derived from grapes, resulted in an increase of HO-1 mRNA, but it was not able to induce HO-1 protein expression and activity. Interestingly, preincubation (12 h) of neurons with EFE resulted in an enhanced cellular resistance to glucose oxidase-mediated oxidative damage; this cytoprotective effect was considerably attenuated by zinc protoporphyrin IX, an inhibitor of HO activity. This study identifies a novel natural compound that could be used for therapeutic purposes as a potent inducer of HO-1 for the protection of brain cells against oxidative and neurodegenerative conditions.
在中枢神经系统中，据报道血红素加氧酶（HO）系统具有活性，并作为暴露于氧化应激挑战的神经元的一种基本防御机制发挥作用。我们最近发现，姜黄素和咖啡酸苯乙酯这两种酚类天然化合物，能在大鼠星形胶质细胞中强烈诱导HO-1的表达和活性。我们扩展了之前的研究结果，检测了另外两种具有类似化学结构的植物源酚类化合物对大鼠星形胶质细胞和神经元的影响。阿魏酸乙酯（4-羟基-3-甲氧基肉桂酸乙酯）（EFE），阿魏酸的天然酯，能够诱导HO-1蛋白表达。在星形胶质细胞中用15 microM EFE孵育6小时以及在神经元中用5 microM EFE孵育6小时后，检测到HO-1 mRNA和蛋白的最大表达以及HO活性显著增加。更高浓度的EFE（50 microM）会产生显著的细胞毒性作用，而HO-1蛋白表达和活性无变化。将星形胶质细胞暴露于白藜芦醇（一种源自葡萄的植物抗毒素）中，会导致HO-1 mRNA增加，但它无法诱导HO-1蛋白表达和活性。有趣的是，神经元用EFE预孵育（12小时）会增强细胞对葡萄糖氧化酶介导的氧化损伤的抗性；这种细胞保护作用被HO活性抑制剂锌原卟啉IX显著减弱。本研究鉴定出一种新型天然化合物，它可作为HO-1的强效诱导剂用于治疗目的，以保护脑细胞免受氧化和神经退行性疾病的侵害。
