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DJ-1缺失通过干扰表皮黑素细胞中线粒体的功能增强氧化应激。

Ablation of DJ-1 Enhances Oxidative Stress by Disturbing the Function of Mitochondria in Epidermal Melanocytes.

作者信息

Li Man, Wang Fang, Du Juan, Wang Lijuan, Zhang Jianzhong, Ding Xiaolan

机构信息

Department of Dermatology, Peking University People's Hospital, Beijing, China.

出版信息

Indian J Dermatol. 2020 Mar-Apr;65(2):85-91. doi: 10.4103/ijd.IJD_593_18.

DOI:10.4103/ijd.IJD_593_18
PMID:32180592
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7059463/
Abstract

BACKGROUND

Oxidative stress is implicated in the pathogenesis of vitiligo. The function of DJ-1 in oxidative damage of melanocytes is still elusive.

AIMS

The aim of this study was to investigate the role of DJ-1 in oxidative damage of melanocytes.

MATERIAL AND METHODS

The expression of DJ-1 in melanocytes was studied by reverse transcription-quantitative polymerase chain reaction and Western blot. Short-interfering RNAs (siRNA) were employed to downregulate DJ-1. The cells were pooled into three groups: mock group (cells with transfection reagent), negative control (NC) group (negative siRNA control), and siRNA group. After HO treatment for 24 h, the morphological changes, cell viability, apoptosis, intracellular reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), and mitochondrial respiration were measured in different groups.

RESULTS

DJ-1 was highly expressed in PIG1 melanocytes. DJ-1 knockdown rendered PIG1 melanocytes more susceptible to oxidative stress. Loss of DJ-1 led to apoptosis of PIG1 cells by impairing the function of mitochondria, including morphological abnormalities, ROS accumulation, depolarization of MMP, less adenosine-triphosphate (ATP) production, and less proton leak.

CONCLUSIONS

DJ-1 plays a role in maintaining the antioxidative capacity in epidermal melanocytes.

摘要

背景

氧化应激与白癜风的发病机制有关。DJ-1在黑素细胞氧化损伤中的作用仍不清楚。

目的

本研究旨在探讨DJ-1在黑素细胞氧化损伤中的作用。

材料与方法

采用逆转录-定量聚合酶链反应和蛋白质免疫印迹法研究DJ-1在黑素细胞中的表达。使用小干扰RNA(siRNA)下调DJ-1。将细胞分为三组:模拟组(转染试剂处理的细胞)、阴性对照组(阴性siRNA对照)和siRNA组。在过氧化氢(HO)处理24小时后,检测不同组细胞的形态变化、细胞活力、凋亡、细胞内活性氧(ROS)水平、线粒体膜电位(MMP)和线粒体呼吸。

结果

DJ-1在PIG1黑素细胞中高表达。DJ-1基因敲低使PIG1黑素细胞对氧化应激更敏感。DJ-1缺失通过损害线粒体功能导致PIG1细胞凋亡,包括形态异常、ROS积累、MMP去极化、三磷酸腺苷(ATP)生成减少和质子泄漏减少。

结论

DJ-1在维持表皮黑素细胞的抗氧化能力中起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e25/7059463/7605d3e24eb0/IJD-65-85-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e25/7059463/3629598a6259/IJD-65-85-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e25/7059463/f52d3324d57c/IJD-65-85-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e25/7059463/7605d3e24eb0/IJD-65-85-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e25/7059463/3629598a6259/IJD-65-85-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e25/7059463/f52d3324d57c/IJD-65-85-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e25/7059463/7605d3e24eb0/IJD-65-85-g003.jpg

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本文引用的文献

1
The Role of the Antioxidant Protein DJ-1 in Type 2 Diabetes Mellitus.抗氧化蛋白DJ-1在2型糖尿病中的作用
Adv Exp Med Biol. 2017;1037:173-186. doi: 10.1007/978-981-10-6583-5_11.
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Vitiligo Pathogenesis and Emerging Treatments.白癜风的发病机制与新兴治疗方法
Dermatol Clin. 2017 Apr;35(2):257-265. doi: 10.1016/j.det.2016.11.014.
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Mitochondrial ROS signaling in organismal homeostasis.线粒体活性氧信号在机体稳态中的作用
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DJ-1 links muscle ROS production with metabolic reprogramming and systemic energy homeostasis in mice.DJ-1将小鼠肌肉活性氧生成与代谢重编程及全身能量稳态联系起来。
Nat Commun. 2015 Jun 16;6:7415. doi: 10.1038/ncomms8415.
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Highlights in pathogenesis of vitiligo.白癜风发病机制要点。
World J Clin Cases. 2015 Mar 16;3(3):221-30. doi: 10.12998/wjcc.v3.i3.221.
6
Decreased DJ-1 leads to impaired Nrf2-regulated antioxidant defense and increased UV-A-induced apoptosis in corneal endothelial cells.DJ-1 减少导致角膜内皮细胞中 Nrf2 调节的抗氧化防御受损和增加 UV-A 诱导的细胞凋亡。
Invest Ophthalmol Vis Sci. 2014 Jul 31;55(9):5551-60. doi: 10.1167/iovs.14-14580.
7
Upregulated Parkin expression protects mitochondrial homeostasis in DJ-1 konckdown cells and cells overexpressing the DJ-1 L166P mutation.Parkin 表达上调可保护 DJ-1 敲低细胞和过表达 DJ-1 L166P 突变细胞中的线粒体动态平衡。
Mol Cell Biochem. 2014 Feb;387(1-2):187-95. doi: 10.1007/s11010-013-1884-3. Epub 2013 Nov 16.
8
Neuroprotective function of DJ-1 in Parkinson's disease.DJ-1 在帕金森病中的神经保护作用。
Oxid Med Cell Longev. 2013;2013:683920. doi: 10.1155/2013/683920. Epub 2013 May 16.
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Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis.氧化应激:细胞凋亡的线粒体依赖性和非线粒体依赖性途径。
Arch Toxicol. 2013 Jul;87(7):1157-80. doi: 10.1007/s00204-013-1034-4. Epub 2013 Mar 30.
10
The Parkinson disease-related protein DJ-1 counteracts mitochondrial impairment induced by the tumour suppressor protein p53 by enhancing endoplasmic reticulum-mitochondria tethering.帕金森病相关蛋白 DJ-1 通过增强内质网-线粒体连接来拮抗肿瘤抑制蛋白 p53 诱导的线粒体损伤。
Hum Mol Genet. 2013 Jun 1;22(11):2152-68. doi: 10.1093/hmg/ddt068. Epub 2013 Feb 14.