Inhibition of the cleaved half of tRNAGly enhances palmitic acid-induced apoptosis in human trophoblasts,The Journal of Nutritional Biochemistry

当前位置： X-MOL 学术 › J. Nutr. Biochem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Inhibition of the cleaved half of tRNAGly enhances palmitic acid-induced apoptosis in human trophoblasts
The Journal of Nutritional Biochemistry ( IF 4.8 ) Pub Date : 2021-09-24 , DOI: 10.1016/j.jnutbio.2021.108866
Changwon Yang ₁ , Sunwoo Park ₂ , Gwonhwa Song ₁ , Whasun Lim ₃

Affiliation

Palmitic acid (PA) induces apoptosis in the human trophoblast cell line HTR8/SVneo. However, the molecular mechanism underlying this effect remains unclear. Although small noncoding RNAs are involved in trophoblast growth and invasion during early pregnancy, the functional roles of tRNA-derived species are currently unknown. Therefore, the purpose of this study was to examine the involvement of tRNA-derived species in PA-induced apoptosis in human trophoblasts. In this study, we investigate the expression and function of tRNA-derived stress-induced RNAs (tiRNAs) in HTR8/SVneo. We determined the expression of tiRNAs in HTR8/SVneo cells in response to PA. Then, we transfected inhibitor of target tiRNA in HTR8/SVneo with or without PA to examine the tRNA-derived species-regulated intracellular signal transduction by detecting calcium homeostasis, mitochondrial membrane potential, and signaling proteins. We found that the expression of tRNA-derived tiRNAs decreased in PA-treated human trophoblasts. Moreover, inhibition of tiRNA enhanced the PA-induced apoptosis along with the induction of DNA fragmentation and mitochondrial depolarization. Inhibition of tiRNA enhanced the expression of endoplasmic reticulum stress-related proteins and increased Ca levels in the cytoplasm and mitochondria. Moreover, the levels of cytochrome c released from the mitochondria were synergistically affected by tiRNA inhibitor and PA. Furthermore, artificial regulation of ANG inhibited the expression of tiRNA and similar effects were observed upon the inhibition of tiRNA in human trophoblasts. These results suggest that tiRNA might be the molecule via which PA induces its effects in human trophoblasts.

中文翻译：

抑制 tRNAGly 的裂解半部可增强棕榈酸诱导的人滋养层细胞凋亡

棕榈酸 (PA) 诱导人滋养层细胞系 HTR8/SVneo 凋亡。然而，这种效应背后的分子机制仍不清楚。尽管小非编码 RNA 参与妊娠早期滋养层的生长和侵袭，但 tRNA 衍生物种的功能作用目前尚不清楚。因此，本研究的目的是检查 tRNA 衍生物种在 PA 诱导的人类滋养层细胞凋亡中的参与情况。在本研究中，我们研究了 HTR8/SVneo 中 tRNA 衍生的应激诱导 RNA (tiRNA) 的表达和功能。我们确定了 HTR8/SVneo 细胞中 tiRNA 响应 PA 的表达。然后，我们在有或没有PA的HTR8/SVneo中转染靶tiRNA抑制剂，通过检测钙稳态、线粒体膜电位和信号蛋白来检查tRNA衍生物种调节的细胞内信号转导。我们发现经 PA 处理的人滋养层中 tRNA 衍生的 tiRNA 的表达下降。此外，tiRNA 的抑制增强了 PA 诱导的细胞凋亡以及 DNA 断裂和线粒体去极化的诱导。 tiRNA 的抑制增强了内质网应激相关蛋白的表达，并增加了细胞质和线粒体中的 Ca 水平。此外，线粒体释放的细胞色素c水平受到tiRNA抑制剂和PA的协同影响。此外，ANG的人工调节抑制了tiRNA的表达，并且在人滋养层中抑制tiRNA时观察到类似的效果。这些结果表明 tiRNA 可能是 PA 在人类滋养层中诱导其作用的分子。

更新日期：2021-09-24

点击分享查看原文

点击收藏

阅读更多本刊最新论文