Acetylation of Retinal Histones in Diabetes Increases Inflammatory Proteins EFFECTS OF MINOCYCLINE AND MANIPULATION OF HISTONE ACETYLTRANSFERASE (HAT) AND HISTONE DEACETYLASE (HDAC)
Acetylation of Retinal Histones in Diabetes Increases Inflammatory Proteins EFFECTS OF MINOCYCLINE AND MANIPULATION OF HISTONE ACETYLTRANSFERASE (HAT) AND HISTONE DEACETYLASE (HDAC)
复制标题
糖尿病患者视网膜组蛋白的乙酰化会增加炎症蛋白的作用米诺环素以及组蛋白乙酰转移酶 (HAT) 和组蛋白脱乙酰酶 (HDAC) 的调控
DOI：
10.1074/jbc.m112.375204
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发表时间：
2012-07-27
影响因子：
4.8
通讯作者：
Kern, Timothy S.
中科院分区：
文献类型：
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作者：
Kadiyala, Chandra Sekhar Rao;Zheng, Ling;Kern, Timothy S.
组蛋白乙酰化在糖尿病大鼠视网膜中显著增加，并且这种乙酰化在用二甲胺四环素治疗的糖尿病患者中被抑制，二甲胺四环素是一种已知抑制动物早期糖尿病视网膜病变的药物。组蛋白乙酰化和炎症蛋白的表达，已牵连在糖尿病视网膜病变的发病机制同样增加培养的视网膜穆勒神经胶质细胞中生长的糖尿病样浓度的葡萄糖。无论是乙酰化和诱导的炎症蛋白在升高的葡萄糖水平显着抑制组蛋白乙酰转移酶抑制剂（garcinol和反义组蛋白乙酰化酶，p300）或组蛋白脱乙酰酶的激活剂（茶碱和白藜芦醇），并增加了组蛋白脱乙酰酶抑制剂，辛二酰苯胺异羟肟酸。我们的结论是高血糖导致视网膜组蛋白（可能还有其他蛋白质）的乙酰化，乙酰化有助于高血糖诱导的促炎蛋白的上调，从而促进糖尿病视网膜病变的发展。
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.