• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Concurrent opposite effects of trichostatin A, an inhibitor of histone deacetylases, on expression of alpha-MHC and cardiac tubulins: implication for gain in cardiac muscle contractility.
【24h】

Concurrent opposite effects of trichostatin A, an inhibitor of histone deacetylases, on expression of alpha-MHC and cardiac tubulins: implication for gain in cardiac muscle contractility.

机译：组蛋白脱乙酰基酶抑制剂曲古抑菌素A对α-MHC和心脏微管蛋白的表达同时产生相反的作用：暗示心肌收缩力增加。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Histone deacetylases (HDACs) are a family of enzymes that catalyze the removal of acetyl groups from core histones, resulting in change of chromatin structure and gene transcription activity. In the heart, HDACs are targets of hypertrophic signaling, and their nonspecific inhibition by trichostatin A (TSA) attenuates hypertrophy of cultured cardiac myocytes. In this study, we examined the effect of TSA on two major determinants of cardiac contractility: alpha-myosin heavy chain (MHC) expression and microtubular composition and organization. TSA upregulated the expression of alpha-MHC in cultured cardiac myocytes, as well as in an in vivo model of hypothyroid rats. Studies designed to delineate mechanisms of alpha-MHC induction by TSA revealed an obligatory role of early growth response factor-1 on activation of the alpha-MHC promoter. Concurrently, TSA downregulated the expression of alpha- and beta-tubulins and prevented the induction of tubulins by a hypertrophy agonist, ANG II. The ANG II-mediated increased proportion of alpha- and beta-tubulins associated with polymerized microtubules was also markedly reduced after treatment of cells by TSA. Results obtained from immunofluorescent microscopy indicated that TSA had no noticeable effect on the organization of cardiac microtubules in control cells, whereas it prevented the ANG II-induced dense parallel linear arrays of microtubules to a profile similar to that of controls. Together, these results demonstrate that inhibition of HDACs by TSA regulates the cardiac alpha-MHC and tubulins in a manner predictive of improved cardiac contractile function. These studies improve our understanding of the role of HDACs on cardiac hypertrophy with implications in development of new therapeutic agents for treatment of cardiac abnormalities.
机译：组蛋白脱乙酰基酶（HDAC）是一类酶，可催化从核心组蛋白中除去乙酰基，从而导致染色质结构和基因转录活性的改变。在心脏中，HDACs是肥大信号的靶标，并且曲古抑菌素A（TSA）对HDAC的非特异性抑制可减弱培养的心肌细胞的肥大。在这项研究中，我们检查了TSA对心脏收缩力的两个主要决定因素的影响：α-肌球蛋白重链（MHC）表达以及微管组成和组织。 TSA上调了培养的心肌细胞以及甲状腺功能减退大鼠的体内模型中α-MHC的表达。旨在描述TSA诱导α-MHC的机制的研究表明，早期生长应答因子1对α-MHC启动子的激活具有强制性作用。同时，TSA下调了α-和β-微管蛋白的表达，并阻止了肥大激动剂ANGII诱导微管蛋白的诱导。用TSA处理细胞后，与聚合微管相关的ANG II介导的α-和β-微管蛋白比例也明显降低。从免疫荧光显微镜获得的结果表明，TSA对对照细胞中的心脏微管的组织没有明显的影响，而它却阻止了ANG II诱导的微管的密集平行线性阵列的分布与对照相似。总之，这些结果表明，TSA对HDAC的抑制以预示心脏收缩功能改善的方式调节心脏α-MHC和微管蛋白。这些研究提高了我们对HDAC在心脏肥大中作用的理解，对开发治疗心脏异常的新治疗剂具有重要意义。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号