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

Changwon Yang, Sunwoo Park, Gwonhwa Song, Whasun Lim

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4 Scopus citations

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
StatePublished - Jan 2022

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea ( NRF ) grant funded by the Korea government(MSIT) (grant number: 2021R1C1C1009807 and 2021R1A2C2005841 ) and supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number: 2020R1I1A1A01067648 ).

Publisher Copyright:
© 2021

Keywords

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

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