Inhibition of mitochondrial proton F0F1-ATPase/ATP synthase by polyphenolic phytochemicals
Inhibition of mitochondrial proton F0F1-ATPase/ATP synthase by polyphenolic phytochemicals
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DOI：
10.1038/sj.bjp.0703397
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发表时间：
2000-07-01
影响因子：
7.3
通讯作者：
Ramirez, VD
中科院分区：
文献类型：
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作者：
Zheng, JB;Ramirez, VD
1线粒体质子FOF 1-ATP酶/ATP合成酶在氧化磷酸化过程中合成ATP。在这项研究中，我们研究了几组多酚植物化学物质对酶活性的影响。2白藜芦醇，一种存在于葡萄和红葡萄酒中的二苯乙烯植物抗毒素，浓度依赖性地抑制大鼠脑和肝FOF 1-ATP酶/ATP合酶的酶活性（IC 50为12-28 μ M）。3使用大鼠脑F0 F1-ATP酶活性筛选其它多酚植物化学物质导致以下等级效力（括号中为IC 50）：白藜芦醇（8 μ M）>白藜芦醇（19 μ M）=（-）表没食子儿茶素没食子酸酯（17 μ M）>（-）表儿茶素没食子酸酯，姜黄素（45 μ M）>染料木黄酮=鹰嘴豆芽素A =槲皮素=山奈酚=桑色素（55 - 65 μ M）>根皮素=芹菜素=大豆苷元（约100 μ M）。染料木苷、槲皮苷、根皮苷、（+）儿茶素、（+）表儿茶素、（-）表儿茶素和（-）表没食子儿茶素在相似浓度下几乎没有影响。单宁酸、茶黄素（茶提取物）和葡萄籽原花青素提取物（GSPE）的IC 50值分别为5、20和30 μ g/ml。几种单酚类抗氧化剂和非酚类化合物在210 μ M或更高的浓度下无效。4白藜芦醇和染料木素对F0 F1-ATP酶的抑制在自然界是非竞争性的。5多酚类植物化学物质的作用是相加的。6白藜芦醇和染料木素对猪大脑皮层Na+/K+-ATP酶活性几乎没有影响，而槲皮素具有与F0 F1-ATP酶类似的抑制效力。7总之，ATP合酶是膳食植物化学物质的靶标。这些植物化学物质的药理学特性应包括在其健康益处以及潜在细胞毒性的检查中。
1 Mitochondrial proton FOF1-ATPase/ATP synthase synthesizes ATP during oxidative phosphorylation. In this study, we examined the effects of several groups of polyphenolic phytochemicals on the activity of the enzyme.2 Resveratrol, a stilbene phytoalexin that is present in grapes and red wine, concentration-dependently inhibited the enzymatic activity of both rat brain and liver FOF1-ATPase/ATP synthase (IC50 of 12-28 mu M).3 Screening of other polyphenolic phytochemicals using rat brain F0F1-ATPase activity resulted in the following ranking potency (IC50 in parenthesis): piceatannol (8 mu M) > resveratrol (19 mu M)= (-)epigallocatechin gallate (17 mu M)>(-)epicatechin gallate, curcumin (45 mu M) > genistein = biochanin A = quercetin = kaempferol = morin (55 - 65 mu M) > phloretin = apigenin = daidzein (approx. 100 mu M). Genistin, quercitrin, phloridzin, (+)catechin, (+)epicatechin, (-)epicatechin and (-)epigallocatechin had little effect at similar concentrations. Tannic acid, theaflavins (tea extract) and grape seed proanthocyanidin extract (GSPE) had IC50 values of 5, 20 and 30 mu g ml(-1), respectively. Several monophenolic antioxidants and non-phenolic compounds were ineffective at concentrations of 210 mu M or higher.4 The inhibition of F0F1-ATPase by resveratrol and genistein was non-competitive in nature.5 The effects of polyphenolic phytochemicals were additive.6 Both resveratrol and genistein had little effect on the Na+/K+-ATPase activity of porcine cerebral cortex, whereas quercetin had similar inhibitory potency as for F0F1-ATPase.7 In conclusion, the ATP synthase is a target for dietary phytochemicals. This pharmacological property of these phytochemicals should be included in the examination of their health benefits as well as potential cytotoxicity.