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黄酮类化合物与线粒体的相互作用:对能量代谢过程的影响。

The interaction of flavonoids with mitochondria: effects on energetic processes.

作者信息

Dorta Daniel J, Pigoso Acácio A, Mingatto Fábio E, Rodrigues Tiago, Prado Ieda M R, Helena Anaísa F C, Uyemura Sérgio A, Santos Antonio C, Curti Carlos

机构信息

Departamento de Física e Química, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av.Café s/n, 14040-903 Ribeirão Preto, São Paulo, Brazil.

出版信息

Chem Biol Interact. 2005 Apr 15;152(2-3):67-78. doi: 10.1016/j.cbi.2005.02.004.

Abstract

The study addressed aspects of energetics of isolated rat liver mitochondria exposed to the flavonoids quercetin, taxifolin, catechin and galangin, taking into account influences of the 2,3 double bond/3-OH group and 4-oxo function on the C-ring, and o-di-OH on the B-ring of their structures, as well as mitochondrial mechanisms potentially involved in cell necrosis and apoptosis. The major findings/hypothesis, were: The 2,3 double bond/3-OH group in conjugation with the 4-oxo function on the C-ring in the flavonoid structure seems favour the interaction of these compounds with the mitochondrial membrane, decreasing its fluidity either inhibiting the respiratory chain of mitochondria or causing uncoupling; while the o-di-OH on the B-ring seems favour the respiratory chain inhibition, the absence of this structure seems favour the uncoupling activity. The flavonoids not affecting the respiration of mitochondria, induced MPT. The ability of flavonoids to induce the release of mitochondria-accumulated Ca(2+) correlated well with their ability to affect mitochondrial respiration on the one hand, and their inability to induce MPT, on the other. The flavonoids causing substantial respiratory chain inhibition or mitochondrial uncoupling, quercetin and galangin, respectively, also decreased the mitochondrial ATP levels, thus suggesting an apparent higher potential for necrosis induction in relation to the flavonoids inducing MPT, taxifolin and cathechin, which did not decrease significantly the ATP levels, rather suggesting an apparent higher potential for apoptosis induction.

摘要

该研究探讨了分离的大鼠肝线粒体在暴露于黄酮类化合物槲皮素、紫杉叶素、儿茶素和高良姜素时的能量代谢方面,考虑了其结构中C环上的2,3双键/3-OH基团和4-氧代官能团以及B环上的邻二羟基的影响,以及可能参与细胞坏死和凋亡的线粒体机制。主要发现/假设如下:黄酮类化合物结构中C环上的2,3双键/3-OH基团与4-氧代官能团结合似乎有利于这些化合物与线粒体膜的相互作用,降低其流动性,要么抑制线粒体呼吸链,要么导致解偶联;而B环上的邻二羟基似乎有利于呼吸链抑制,缺乏该结构似乎有利于解偶联活性。这些黄酮类化合物不影响线粒体的呼吸作用,但会诱导线粒体通透性转换(MPT)。黄酮类化合物诱导线粒体积累的Ca(2+)释放的能力一方面与其影响线粒体呼吸的能力密切相关,另一方面与其不能诱导MPT的能力密切相关。分别导致显著呼吸链抑制或线粒体解偶联的黄酮类化合物槲皮素和高良姜素,也降低了线粒体ATP水平,因此表明与诱导MPT的黄酮类化合物紫杉叶素和儿茶素相比,它们诱导坏死的潜力明显更高,后者并未显著降低ATP水平,反而表明其诱导凋亡的潜力明显更高。

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