当前位置： SCI文献检索 > Cell Death & Disease期刊下所有文献 > A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis.

A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis.

Abstract：

:Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspase-dependent apoptosis through miRNA-101-3p downregulation, without altering expression of its host gene RNA 3'-terminal phosphate cyclase-like 1, which was highly correlated with suppressed expression levels of Dicer and Argonaute 2 (Ago2), indicating that miR-101-3p is post-transcriptionally elevated in serum-deprived conditions. The decreased miR-101-3p caused elevated Bim expression by targeting its 3'-untranslated region (3'-UTR). This resulted in activation of the intrinsic pathway of apoptosis via interaction with Bcl-2, decreased mitochondrial membrane potential, cytochrome c release, mitochondrial reactive oxygen species (ROS) production, and caspase activation. These events were abrogated by miR-101-3p mimic and the proapoptotic Bim siRNA, which suggest a determinant role of the miR-101-3p/Bim axis in serum deprivation-induced apoptosis. The apoptosis induced by miR-101-3p-mediated Bim expression is mediated by both caspase-3 and -1, which are activated by two distinct intrinsic mechanisms, cytochrome c release and ROS-induced inflammasome activation, respectively. In other words, the antioxidant inhibited endothelial cell death mediated by caspase-1 that activated caspase-7, but not caspase-3. These findings provide mechanistic insight into a novel function of miR-101-3p in serum withdrawal-induced apoptosis triggered by activating two different intrinsic or mitochondrial apoptosis pathways, implicating miR-101-3p as a therapeutic target that limits endothelial cell death associated with vascular disorders.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Kim JH,Lee DK,Kim J,Choi S,Park W,Ha KS,Kim TH,Choe J,Won MH,Kwon YG,Kim YM

doi

10.1038/cddis.2017.219

subject

Has Abstract

pub_date

2017-05-18 00:00:00

pages

e2808

issue

issn

2041-4889

pii

cddis2017219

journal_volume

pub_type

杂志文章

在线工具

A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis.