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糖尿病大鼠视网膜组蛋白甲基化水平异常，米诺环素治疗可逆转。

Abnormal levels of histone methylation in the retinas of diabetic rats are reversed by minocycline treatment.

机构信息

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan, 430072, P.R. China.

Department of Biochemistry and Molecular Biology and VILLUM Center for Bioanalytical Sciences, University of Southern Denmark, DK-5230 Odense M, Denmark.

出版信息

Sci Rep. 2017 Mar 24;7:45103. doi: 10.1038/srep45103.

DOI:10.1038/srep45103
PMID:28338045
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5364468/
Abstract

In this study we quantified the alterations of retinal histone post-translational modifications (PTMs) in diabetic rats using a liquid chromatography - tandem mass spectrometry (LC-MS/MS) approach. Some diabetic rats were subsequently treated with minocycline, a tetracycline antibiotic, which has been shown to inhibit the diabetes-induced chronic inflammation in the retinas of rodents. We quantified 266 differentially modified histone peptides, including 48 out of 83 methylation marks with significantly different abundancein retinas of diabetic rats as compared to non-diabetic controls. About 67% of these marks had their relative abundance restored to non-diabetic levels after minocycline treatment. Mono- and di-methylation states of histone H4 lysine 20 (H4K20me1/me2), markers related to DNA damage response, were found to be up-regulated in the retinas of diabetic rats and restored to control levels upon minocycline treatment. DNA damage response biomarkers showed the same pattern once quantified by western blotting. Collectively, this study indicates that alteration of some histone methylation levels is associated with the development of diabetic retinopathy in rodents, and the beneficial effect of minocycline on the retinas of diabetic rodents is partially through its ability to normalize the altered histone methylation levels.

摘要

在这项研究中，我们使用液相色谱-串联质谱（LC-MS/MS）方法定量了糖尿病大鼠视网膜组蛋白翻译后修饰（PTMs）的变化。随后，一些糖尿病大鼠用米诺环素（一种四环素抗生素）治疗，该抗生素已被证明可抑制啮齿动物视网膜中糖尿病引起的慢性炎症。我们定量了 266 种差异修饰的组蛋白肽，包括 83 种甲基化标记中的 48 种，与非糖尿病对照组相比，糖尿病大鼠视网膜中的丰度有显著差异。大约 67%的这些标记在米诺环素治疗后其相对丰度恢复到非糖尿病水平。与 DNA 损伤反应相关的组蛋白 H4 赖氨酸 20 的单甲基化和二甲基化状态（H4K20me1/me2）在糖尿病大鼠的视网膜中上调，并在米诺环素治疗后恢复到对照水平。用 Western blot 定量时，DNA 损伤反应生物标志物也表现出相同的模式。总的来说，这项研究表明，一些组蛋白甲基化水平的改变与啮齿动物糖尿病性视网膜病变的发展有关，米诺环素对糖尿病啮齿动物视网膜的有益作用部分是通过其使改变的组蛋白甲基化水平正常化的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/75f8d9f9a270/srep45103-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/5973971be05d/srep45103-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/bd7d991a8574/srep45103-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/26c115bf3b74/srep45103-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/e062c92d9c01/srep45103-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/75f8d9f9a270/srep45103-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/5973971be05d/srep45103-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/e7da8c7dbf04/srep45103-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/ae2f32138bdc/srep45103-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/bd7d991a8574/srep45103-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/26c115bf3b74/srep45103-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/e062c92d9c01/srep45103-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78f9/5364468/75f8d9f9a270/srep45103-f7.jpg

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