Acetylation of retinal histones in diabetes increases inflammatory proteins: Effects of minocycline and manipulation of histone acetyltransferase (HAT) and histone deacetylase (HDAC)

Chandra Sekhar Rao Kadiyala, Ling Zheng, Yunpeng Du, Elizabeth Yohannes, Hung Ying Kao, Masaru Miyagi, Timothy S. Kern

研究成果: Article

73 引文 斯高帕斯(Scopus)

摘要

Histone acetylation was significantly increased in retinas from diabetic rats, and this acetylation was inhibited in diabetics treated with minocycline, a drug known to inhibit early diabetic retinopathy in animals. Histone acetylation and expression of inflammatory proteins that have been implicated in the pathogenesis of diabetic retinopathy were increased likewise in cultured retinal Müller glia grown in a diabetes-like concentration of glucose. Both the acetylation and induction of the inflammatory proteins in elevated glucose levels were significantly inhibited by inhibitors of histone acetyltransferase (garcinol and antisense against the histone acetylase, p300) or activators of histone deacetylase (theophylline and resveratrol) and were increased by the histone deacetylase inhibitor, suberolylanilide hydroxamic acid. We conclude that hyperglycemia causes acetylation of retinal histones (and probably other proteins) and that the acetylation contributes to the hyperglycemia-induced upregulation of proinflammatory proteins and thereby to the development of diabetic retinopathy.

原文English
頁(從 - 到)25869-25880
頁數12
期刊Journal of Biological Chemistry
287
發行號31
DOIs
出版狀態Published - 2012 七月 27

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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