The Parkinsonism-associated protein DJ-1/Park7 prevents glycation damage in human keratinocyte
The Parkinsonism-associated protein DJ-1/Park7 prevents glycation damage in human keratinocyte
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DOI：
10.1016/j.bbrc.2016.03.056
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发表时间：
2016-04-22
影响因子：
3.1
通讯作者：
Richarme, Gilbert
中科院分区：
文献类型：
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作者：
Advedissian, Tamara;Deshayes, Frederique;Richarme, Gilbert
还原糖和二羰基化合物通过称为糖化的非酶过程与蛋白质形成共价加合物，糖化使蛋白质失活，在糖尿病患者中增加，并与糖尿病并发症有关，包括视网膜病变、白内障、肾病、神经病变、心肌病和皮肤缺损。我们最近将DJ-1/Park 7描述为一种蛋白质脱糖酶，可以修复蛋白质被乙二醛和甲基乙二醛（两种主要的糖基化剂，导致高达65%的糖基化事件）的糖基化。在这项研究中，我们研究了DJ-1的能力防止角质形成细胞中的蛋白质糖基化。胶原蛋白和角质形成细胞蛋白的糖基化通过测量紫外吸收和荧光发射来测试。HaCaT角质形成细胞中的蛋白质糖基化通过用抗晚期糖基化终产物抗体的免疫检测来研究，在DJ-1耗尽或过表达之后。在体外，DJ-1阻止胶原蛋白和角质形成细胞蛋白提取物的糖化。在细胞培养中，小干扰RNA导致DJ-1耗竭导致蛋白质糖化水平增加3倍。此外，在加入Nrf 2诱导剂萝卜硫素或用DJ-1质粒转染后，过表达DJ-1的细胞中蛋白质糖化水平降低了数倍。因此，DJ-1 deglycase在防止真核细胞中的蛋白质糖化中起主要作用，并且可能对于防止皮肤糖化是重要的。(C)2016 Elsevier Inc. All rights reserved.
Reducing sugars and dicarbonyls form covalent adducts with proteins through a nonenzymatic process known as glycation, which inactivates proteins, is increased in diabetic patients and is associated with diabetic complications, including retinopathy, cataracts, nephropathy, neuropathy, cardiomyopathy and skin defects. We recently characterized DJ-1/Park7 as a protein deglycase that repairs proteins from glycation by glyoxal and methylglyoxal, two major glycating agents which are responsible for up to 65% of glycation events.In this study, we investigated the ability of DJ-1 to prevent protein glycation in keratinocytes. Glycation of collagen and keratinocyte proteins was tested by measuring ultraviolet absorption and fluorescence emission. Protein glycation in HaCaT keratinocytes was investigated by immunodetection with anti advanced glycation endproduct antibodies, after DJ-1 depletion or overexpression. In vitro, DJ-1 prevented glycation of collagen and keratinocyte protein extracts. In cell culture, DJ-1 depletion by small interfering RNAs resulted in a 3-fold increase in protein glycation levels. Moreover, protein glycation levels were decreased several-fold in cells overexpressing DJ-1 after addition of the Nrf2 inducer sulforaphane or after transfection with a DJ-1 plasmid. Thus, the DJ-1 deglycase plays a major role in preventing protein glycation in eukaryotic cells and might be important for preventing skin glycation. (C) 2016 Elsevier Inc. All rights reserved.