Insulin induced alteration in post-translational modifications of histone H3 under a hyperglycemic condition in L6 skeletal muscle myoblasts.
Insulin induced alteration in post-translational modifications of histone H3 under a hyperglycemic condition in L6 skeletal muscle myoblasts.
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DOI：
10.1016/j.bbadis.2009.03.003
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发表时间：
2009-06-01
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影响因子：
--
通讯作者：
Tikoo, Kulbhushan
中科院分区：
文献类型：
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作者：
Kabra, Dhiraj G;Gupta, Jeena;Tikoo, Kulbhushan
染色质重塑事件，特别是组蛋白修饰被认为是大多数生物过程的主要组成部分。然而，这些组蛋白修饰在糖尿病进展中的作用仍然未知。高血糖在糖尿病及其并发症中起着重要作用。本研究旨在检查胰岛素对高血糖状态下L6成肌细胞组蛋白H3翻译后修饰改变的影响。我们提供了第一个证据，证明在高血糖状态下胰岛素通过增强活性氧的产生来改变多种组蛋白修饰。胰岛素诱导组蛋白H3的赖氨酸4和9甲基化、丝氨酸10磷酸化和乙酰化发生剂量依赖性变化。有趣的是，胰岛素诱导活性氧的产生可诱导组蛋白H3的去磷酸化和去乙酰化。过氧化氢酶和DPI预孵育可阻止组蛋白H3翻译后修饰的这些变化。此外，发现组蛋白H3磷酸化的变化与ERK、p38、RSK2和MSK1无关。此外，丝氨酸/苏氨酸磷酸酶抑制剂冈田酸可减弱胰岛素诱导的组蛋白H3的去磷酸化和去乙酰化，提示丝氨酸/苏氨酸磷酸酶在改变组蛋白H3修饰中的作用。这些表观遗传修饰的变化可以为糖尿病的发病机制提供新的见解。
Chromatin remodelling events, especially histone modifications are proposed to form the mainstay for most of the biological processes. However, the role of these histone modifications in the progression of diabetes is still unknown. Hyperglycemia plays a major role in diabetes and its complications. The present study was undertaken to check the effect of insulin on alterations in post-translational modifications of histone H3 in L6 myoblasts under a hyperglycemic condition. We provide first evidence that insulin under hyperglycemic condition alters multiple histone modifications by enhanced production of reactive oxygen species. Insulin induces dose dependent changes in Lysine 4 and 9 methylation, Ser 10 phosphorylation and acetylation of histone H3. Interestingly, insulin induced generation of reactive oxygen species induces dephosphorylation and deacetylation of histone H3. Preincubation with catalase and DPI prevents these changes in post-translational modifications of histone H3. Furthermore, changes in histone H3 phosphorylation was found to be independent of ERK, p38, RSK2 and MSK1. Moreover, serine/threonine phosphatase inhibitor, okadaic acid attenuates insulin induced dephosphorylation and deacetylation of histone H3, suggesting a role of serine/threonine phosphatases in altering modifications of histone H3. These changes in epigenetic modifications can provide new insights into pathogenesis of diabetes.