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

Wenjun Wang, Simone Sidoli, Wenquan Zhang, Qing Wang, Leilei Wang, Ole N. Jensen, Lin Guo, Xiaolu Zhao, Ling Zheng

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number45103
JournalScientific Reports
Volume7
DOIs
StatePublished - Mar 24 2017
Externally publishedYes

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Minocycline
Histones
Methylation
Retina
Rodentia
DNA Damage
Diabetic Retinopathy
Post Translational Protein Processing
Tandem Mass Spectrometry
Tetracycline
Liquid Chromatography
Lysine
Biomarkers
Western Blotting
Anti-Bacterial Agents
Inflammation
Peptides

ASJC Scopus subject areas

  • General

Cite this

Abnormal levels of histone methylation in the retinas of diabetic rats are reversed by minocycline treatment. / Wang, Wenjun; Sidoli, Simone; Zhang, Wenquan; Wang, Qing; Wang, Leilei; Jensen, Ole N.; Guo, Lin; Zhao, Xiaolu; Zheng, Ling.

In: Scientific Reports, Vol. 7, 45103, 24.03.2017.

Research output: Contribution to journalArticle

Wang, Wenjun ; Sidoli, Simone ; Zhang, Wenquan ; Wang, Qing ; Wang, Leilei ; Jensen, Ole N. ; Guo, Lin ; Zhao, Xiaolu ; Zheng, Ling. / Abnormal levels of histone methylation in the retinas of diabetic rats are reversed by minocycline treatment. In: Scientific Reports. 2017 ; Vol. 7.
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