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

Changwon Yang, Sunwoo Park, Gwonhwa Song, Whasun Lim

Research output: Contribution to journalArticlepeer-review

Abstract

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 tRNAGly-derived tiRNAs decreased in PA-treated human trophoblasts. Moreover, inhibition of tiRNAGlyCCC/GCC enhanced the PA-induced apoptosis along with the induction of DNA fragmentation and mitochondrial depolarization. Inhibition of tiRNAGlyCCC/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 tiRNAGlyCCC/GCC inhibitor and PA. Furthermore, artificial regulation of ANG inhibited the expression of tiRNAGlyCCC/GCC and similar effects were observed upon the inhibition of tiRNAGlyCCC/GCC in human trophoblasts. These results suggest that tiRNAGlyCCC/GCC might be the molecule via which PA induces its effects in human trophoblasts.

Original languageEnglish
Article number108866
JournalJournal of Nutritional Biochemistry
Volume99
DOIs
Publication statusPublished - 2022 Jan

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Fingerprint

Dive into the research topics of 'Inhibition of the cleaved half of tRNA<sup>Gly</sup> enhances palmitic acid-induced apoptosis in human trophoblasts'. Together they form a unique fingerprint.

Cite this