4.7 Article

Inhibition of the cleaved half of tRNAGly enhances palmitic acid-induced apoptosis in human trophoblasts

Journal

JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 99, Issue -, Pages -

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2021.108866

Keywords

trophoblast; tRNA halves; Angiogenin; Apoptosis; Palmitic acid; Trophoblast

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This study investigated the role of tRNA-derived stress-induced RNAs (tiRNAs) in PA-induced apoptosis in human trophoblasts. The findings suggest that the tiRNA(GlyCCC/GCC) molecule may be involved in mediating the effects of PA on human trophoblasts, impacting intracellular signal transduction pathways and calcium homeostasis.
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(Gly)-derived tiRNAs decreased in PA-treated human trophoblasts. Moreover, inhibition of tiRNA(GlyCCC/GCC) enhanced the PA-induced apoptosis along with the induction of DNA fragmentation and mitochondrial depolarization. Inhibition of tiRNA(GlyCCC/GCC) enhanced the expression of endoplasmic reticulum stress-related proteins and increased Ca2+ levels in the cytoplasm and mitochondria. Moreover, the levels of cytochrome c released from the mitochondria were synergistically affected by tiRNA(GlyCCC/GCC) inhibitor and PA. Furthermore, artificial regulation of ANG inhibited the expression of tiRNA(GlyCCC/GCC) and similar effects were observed upon the inhibition of tiRNA(GlyCCC/GCC) in human trophoblasts. These results suggest that tiRNA(GlyCCC/GCC) might be the molecule via which PA induces its effects in human trophoblasts. (C) 2021 Elsevier Inc. All rights reserved.

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