Autophagy and mitochondrial alterations in human retinal pigment epithelial cells induced by ethanol: implications of 4-hydroxy-nonenal.
Autophagy and mitochondrial alterations in human retinal pigment epithelial cells induced by ethanol: implications of 4-hydroxy-nonenal.
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DOI：
10.1038/cddis.2014.288
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发表时间：
2014-07-17
影响因子：
9
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视网膜色素上皮的位置和代谢在视网膜的生理和病理生理中起着至关重要的作用。氧化损伤已被证明是几种视网膜疾病的致病机制，而活性氧是乙醇代谢的重要副产物。自噬在不同的细胞和动物模型中显示出保护作用。因此，在我们的模型中，EtOH处理以浓度依赖的方式增加自噬通量。线粒体形态似乎在EtOH暴露下明显改变，导致线粒体裂变明显增加。2 ',7 ' -二氯荧光素荧光增加，脂质过氧化产物积累，如4-羟基壬烯醛（4-HNE）等均得到证实。这些结构的特性证实了它们是聚合体的性质。因此，自噬似乎在EtOH损伤的ARPE-19细胞中具有细胞保护作用，通过降解碎片化线粒体和4-HNE聚合体。在本文中，我们描述了EtOH诱导氧化应激时人视网膜色素上皮细胞自噬的中心含义，以及可能对其他病症和疾病的影响。
Retinal pigment epithelium has a crucial role in the physiology and pathophysiology of the retina due to its location and metabolism. Oxidative damage has been demonstrated as a pathogenic mechanism in several retinal diseases, and reactive oxygen species are certainly important by-products of ethanol (EtOH) metabolism. Autophagy has been shown to exert a protective effect in different cellular and animal models. Thus, in our model, EtOH treatment increases autophagy flux, in a concentration-dependent manner. Mitochondrial morphology seems to be clearly altered under EtOH exposure, leading to an apparent increase in mitochondrial fission. An increase in 2′,7′-dichlorofluorescein fluorescence and accumulation of lipid peroxidation products, such as 4-hydroxy-nonenal (4-HNE), among others were confirmed. The characterization of these structures confirmed their nature as aggresomes. Hence, autophagy seems to have a cytoprotective role in ARPE-19 cells under EtOH damage, by degrading fragmented mitochondria and 4-HNE aggresomes. Herein, we describe the central implication of autophagy in human retinal pigment epithelial cells upon oxidative stress induced by EtOH, with possible implications for other conditions and diseases.