Acetylation of Retinal Histones in Diabetes Increases Inflammatory Proteins EFFECTS OF MINOCYCLINE AND MANIPULATION OF HISTONE ACETYLTRANSFERASE (HAT) AND HISTONE DEACETYLASE (HDAC)

作者:Kadiyala Chandra Sekhar Rao; Zheng Ling; Du Yunpeng; Yohannes Elizabeth; Kao Hung Ying; Miyagi Masaru*; Kern Timothy S
来源:Journal of Biological Chemistry, 2012, 287(31): 25869-25880.
DOI:10.1074/jbc.M112.375204

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 Muller 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 up-regulation of proinflammatory proteins and thereby to the development of diabetic retinopathy.