MicroRNA-1 participates in nitric oxide-induced apoptotic insults to MC3T3-E1 cells by targeting heat-shock protein-70.
MicroRNA-1 participates in nitric oxide-induced apoptotic insults to MC3T3-E1 cells by targeting heat-shock protein-70.
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DOI：
10.7150/ijbs.11138
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发表时间：
2015
影响因子：
9.2
通讯作者：
Chen RM
中科院分区：
文献类型：
--
作者：
Lee YE;Hong CY;Lin YL;Chen RM
我们前期的研究表明一氧化氮（nitric oxide，NO）可诱导成骨细胞凋亡。MicroRNA-1（miR-1）是一种骨骼肌和心肌特异性小分子非编码RNA，参与多种细胞活动的调控。本研究旨在探讨miR-1在NO诱导的成骨细胞损伤中的作用及其可能机制。小鼠MC 3 T3-E1细胞暴露于硝普钠（SNP）增加细胞内NO和细胞内活性氧的量。随后，SNP降低细胞存活率，但诱导caspase-3激活，DNA片段化和细胞凋亡。与此同时，用SNP处理以时间依赖性方式诱导miR-1表达。miR-1反义抑制剂对成骨细胞的应用引起SNP诱导的miR-1表达的显著抑制。敲低miR-1同时减弱SNP诱导的细胞形态和存活的改变。SNP呈时间依赖性抑制热休克蛋白（HSP）-70信使RNA和蛋白表达。生物信息学搜索预测HSP-70 mRNA的3 '-非翻译区中存在miR-1特异性结合元件。miR-1表达下调同时减轻SNP诱导的HSP-70 mRNA和蛋白表达抑制。因此，SNP诱导的线粒体膜电位、caspase-3激活、DNA片段化和凋亡损伤的改变被miR-1反义抑制剂显著减轻。因此，本研究表明miR-1通过靶向HSP-70基因表达参与NO诱导的细胞凋亡损伤。
Our previous studies showed that nitric oxide (NO) could induce osteoblast apoptosis. MicroRNA-1 (miR-1), a skeletal- and cardiac muscle-specific small non-coding RNA, contributes to the regulation of multiple cell activities. In this study, we evaluated the roles of miR-1 in NO-induced insults to osteoblasts and the possible mechanisms. Exposure of mouse MC3T3-E1 cells to sodium nitroprusside (SNP) increased amounts of cellular NO and intracellular reactive oxygen species. Sequentially, SNP decreased cell survival but induced caspase-3 activation, DNA fragmentation, and cell apoptosis. In parallel, treatment with SNP induced miR-1 expression in a time-dependent manner. Application of miR-1 antisense inhibitors to osteoblasts caused significant inhibition of SNP-induced miR-1 expression. Knocking down miR-1 concurrently attenuated SNP-induced alterations in cell morphology and survival. Consecutively, SNP time-dependently inhibited heat-shock protein (HSP)-70 messenger (m)RNA and protein expressions. A bioinformatic search predicted the existence of miR-1-specific binding elements in the 3'-untranslational region of HSP-70 mRNA. Downregulation of miR-1 expression simultaneously lessened SNP-induced inhibition of HSP-70 mRNA and protein expressions. Consequently, SNP-induced modifications in the mitochondrial membrane potential, caspase-3 activation, DNA fragmentation, and apoptotic insults were significantly alleviated by miR-1 antisense inhibitors. Therefore, this study showed that miR-1 participates in NO-induced apoptotic insults through targeting HSP-70 gene expression.
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