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异甘草素通过抑制 A375 人黑素瘤细胞中的 mitoNEET 以依赖活性氧的方式诱导线粒体功能障碍和细胞凋亡。

Isoliquiritigenin Induces Mitochondrial Dysfunction and Apoptosis by Inhibiting mitoNEET in a Reactive Oxygen Species-Dependent Manner in A375 Human Melanoma Cells.

机构信息

School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai, 264003 Shandong, China.

Key Laboratory of Xinjiang Endemic Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi, 832002 Xinjiang, China.

出版信息

Oxid Med Cell Longev. 2019 Jan 21;2019:9817576. doi: 10.1155/2019/9817576. eCollection 2019.

DOI:10.1155/2019/9817576
PMID:30805086
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6360568/
Abstract

The mitochondrial protein mitoNEET is a type of iron-sulfur protein localized to the outer membrane of mitochondria and is involved in a variety of human pathologies including cystic fibrosis, diabetes, muscle atrophy, and neurodegeneration. In the current study, we found that isoliquiritigenin (ISL), one of the components of the root of , could decrease the expression of mitoNEET in A375 melanoma cells. We also demonstrated that mitoNEET could regulate the content of reactive oxygen species (ROS), by showing that the ISL-mediated increase in the cellular ROS content could be mitigated by the mitoNEET overexpression. We also confirmed the important role of ROS in ISL-treated A375 cells. The increased apoptosis rate and the decreased mitochondrial membrane potential were mitigated by the overexpression of mitoNEET in A375 cells. These findings indicated that ISL could decrease the expression of mitoNEET, which regulated ROS content and subsequently induced mitochondrial dysfunction and apoptosis in A375 cells. Our findings also highlight mitoNEET as a promising mitochondrial target for cancer therapy.

摘要

线粒体蛋白 mitoNEET 是一种位于线粒体外膜的铁硫蛋白,参与多种人类疾病,包括囊性纤维化、糖尿病、肌肉萎缩和神经退行性变。在本研究中,我们发现甘草中的一种成分异甘草素(ISL)可以降低 A375 黑色素瘤细胞中 mitoNEET 的表达。我们还表明,mitoNEET 可以通过显示 ISL 介导的细胞 ROS 含量增加可以通过 mitoNEET 的过表达来缓解,从而调节活性氧(ROS)的含量。我们还证实了 ROS 在 ISL 处理的 A375 细胞中的重要作用。在 A375 细胞中过表达 mitoNEET 可以减轻细胞凋亡率的增加和线粒体膜电位的降低。这些发现表明,ISL 可以降低 mitoNEET 的表达,从而调节 ROS 含量,随后诱导 A375 细胞中线粒体功能障碍和细胞凋亡。我们的研究结果还强调了 mitoNEET 作为癌症治疗的有前途的线粒体靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6d7/6360568/b7dfa40ff71b/OMCL2019-9817576.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6d7/6360568/9d7e5082b71b/OMCL2019-9817576.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6d7/6360568/74aac5723d7f/OMCL2019-9817576.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6d7/6360568/1836c18210d3/OMCL2019-9817576.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6d7/6360568/b7dfa40ff71b/OMCL2019-9817576.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6d7/6360568/9d7e5082b71b/OMCL2019-9817576.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6d7/6360568/74aac5723d7f/OMCL2019-9817576.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6d7/6360568/1836c18210d3/OMCL2019-9817576.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6d7/6360568/b7dfa40ff71b/OMCL2019-9817576.004.jpg

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