奶油
重氮氧化物
磷酸化
激活转录因子
免疫印迹
活性氧
化学
转录因子
内分泌学
内科学
蛋白激酶A
激酶
下调和上调
细胞生物学
生物
医学
生物化学
胰岛素
基因
作者
Gayathri Narasimhan,Elba D. Carrillo,Ascención Hernández,Maria C. García,Jorge A. Sánchez
标识
DOI:10.1097/fjc.0000000000000619
摘要
The effects of diazoxide on cardiac hypertrophy and miR-132 expression were characterized in adult rats and in cardiomyocytes. Diazoxide effects on reactive oxygen species (ROS) production and on the cAMP-response element binding (CREB) transcription factor's abundance in cardiomyocytes were also analyzed. ROS measurements used a fluorescent dye. Western blot analysis and quantitative Reverse Transcription Polymerase Chain Reaction were used to measure phosphorylated form of CREB (pCREB) abundance and miR-132 expression, respectively.Isoproterenol (ISO) induced cardiac hypertrophy, an effect that was mitigated by diazoxide. The rate of ROS production, CREB phosphorylation, and miR-132 expression increased after the addition of ISO. H2O2 increased pCREB abundance and miR-132 expression; upregulation of miR-132 was blocked by the specific inhibitor of CREB transcription, 666-15. Consistent with a role of ROS on miR-132 expression, diazoxide prevented the increase in ROS production, miR-132 expression, and pCREB abundance produced by ISO. Phosphorylation of CREB by ISO was prevented by U0126, an inhibitor of mitogen-activated protein kinase.Our data first demonstrate that diazoxide mitigates hypertrophy by preventing an increase in miR-132 expression. The mechanism likely involves less ROS production leading to less phosphorylation of CREB. Our data further show that ROS enhance miR-132 transcription, and that ISO effects are probably mediated by the mitogen-activated protein kinase pathway.
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