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反,反-2,4-癸二烯醛诱导线粒体功能障碍和氧化应激。

trans,trans-2,4-decadienal induces mitochondrial dysfunction and oxidative stress.

作者信息

Sigolo Carlos A O, Di Mascio Paolo, Kowaltowski Alicia J, Garcia Camila C M, Medeiros Marisa H G

机构信息

Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, Av. Prof. Lineu Prestes 748, CEP 05508-900, São Paulo, Brazil.

出版信息

J Bioenerg Biomembr. 2008 Apr;40(2):103-9. doi: 10.1007/s10863-008-9137-y. Epub 2008 Mar 27.

Abstract

Lipid peroxidation produces a large number of reactive aldehydes as secondary products. We have previously shown that the reaction of cytochrome c with trans,trans-2,4-decadienal (DDE), an aldehyde generated as a product of lipid peroxidation in cell membranes, results in the formation of adducts. Mass spectrometry analysis indicated that His-33, Lys-39, Lys-72 and Lys-100 in cytochrome c were modified by DDE. In the present work, we investigated the effect of DDE on isolated rat liver mitochondria. DDE (162 microM) treatment increases the rate of mitochondrial oxygen consumption. Extensive mitochondrial swelling upon treatment with DDE (900 nM-162 microM) was observed by light scattering and transmission electron microscopy experiments. DDE-induced loss of inner mitochondrial membrane potentials, monitored by safranin O fluorescence, was also observed. Furthermore, DDE-treated mitochondria showed an increase in lipid peroxidation, as monitored by MDA formation. These results suggest that reactive aldehydes promote mitochondrial dysfunction.

摘要

脂质过氧化作用会产生大量作为次级产物的反应性醛类。我们之前已经表明,细胞色素c与反,反-2,4-癸二烯醛(DDE)(一种细胞膜脂质过氧化作用产生的醛类)反应会导致加合物的形成。质谱分析表明,细胞色素c中的组氨酸-33、赖氨酸-39、赖氨酸-72和赖氨酸-100被DDE修饰。在本研究中,我们研究了DDE对分离的大鼠肝脏线粒体的影响。DDE(162微摩尔)处理会增加线粒体的耗氧率。通过光散射和透射电子显微镜实验观察到,用DDE(900纳摩尔 - 162微摩尔)处理后线粒体出现广泛肿胀。还观察到通过番红O荧光监测的DDE诱导的线粒体内膜电位丧失。此外,通过丙二醛形成监测发现,经DDE处理的线粒体脂质过氧化作用增加。这些结果表明,反应性醛类会促进线粒体功能障碍。

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