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白藜芦醇诱导旋毛形纤毛虫线粒体改变、自噬和类似隐生状态。

Resveratrol induces mitochondrial alterations, autophagy and a cryptobiosis-like state in scuticociliates.

机构信息

Laboratorio de Parasitología, Departamento de Microbiología y Parasitología, Instituto de Investigación y Análisis Alimentarios, Universidad de Santiago de Compostela, c/Constantino Candeira s/n, 15782, Santiago de Compostela (La Coruña), Spain.

出版信息

Protist. 2009 Nov;160(4):552-64. doi: 10.1016/j.protis.2009.04.004. Epub 2009 Jul 28.

DOI:10.1016/j.protis.2009.04.004
PMID:19640787
Abstract

The phytoalexin resveratrol (RESV), a defensive substance produced by plants in response to infection by pathogenic microorganisms, displays a wide range of biological effects in mammalian cells. In the present study, we analysed the in vitro effect of RESV on the amphizoic ciliate Philasterides dicentrarchi and demonstrated for the first time that this polyphenol causes cellular and metabolic abnormalities that generate an autophagic process and a state similar to cryptobiosis in the ciliate. At concentrations between 50 and 100 microM, RESV had a cytocidal effect when the ciliate was grown in medium with low levels of nutrients, and a cytostatic effect when the parasite was grown in culture media rich in nutrients. At these concentrations, RESV induced alterations in mitochondria, generated autophagy, provoked a reduction in the cell volume, and also drastically reduced the ciliate endocytic activity in small ciliates, generating a state compatible with cryptobiosis. The results demonstrate that RESV is a potent inducer of autophagy in the scuticociliate P. dicentrarchi. The ciliate may therefore be a good experimental organism for identifying autophagy-inducing drugs with therapeutic potential in diseases in which autophagy plays a protective role.

摘要

植物抗毒素白藜芦醇(RESV)是植物受到致病微生物感染时产生的一种防御物质,它在哺乳动物细胞中显示出广泛的生物学效应。在本研究中,我们分析了 RESV 对兼性纤毛虫 Philasterides dicentrarchi 的体外效应,并首次证明这种多酚会导致细胞和代谢异常,从而产生自噬过程和纤毛虫类似隐生的状态。在浓度为 50 至 100μM 时,当纤毛虫在营养水平低的培养基中生长时,RESV 具有细胞毒性作用,而当寄生虫在富含营养的培养基中生长时,RESV 则具有细胞抑制作用。在这些浓度下,RESV 会引起线粒体的改变,产生自噬,导致细胞体积减小,并且还会极大地降低小纤毛虫的内吞作用活性,从而产生与隐生状态相容的状态。结果表明,RESV 是 scuticociliate P. dicentrarchi 中自噬的有效诱导剂。因此,纤毛虫可能是一种很好的实验生物,可用于鉴定具有在自噬起保护作用的疾病中具有治疗潜力的自噬诱导药物。

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