Endoplasmic reticulum stress disrupts lysosomal homeostasis and induces blockade of autophagic flux in human trophoblasts

Akitoshi Nakashima, Shi Bin Cheng, Tae Kusabiraki, Kenichiro Motomura, Aiko Aoki, Akemi Ushijima, Yosuke Ono, Sayaka Tsuda, Tomoko Shima, Osamu Yoshino, Haruhiko Sago, Kenji Matsumoto, Surendra Sharma, Shigeru Saito

Research output: Contribution to journalArticlepeer-review

Abstract

Pregnancy is a stress factor culminating into mild endoplasmic reticulum (ER) stress, which is necessary for placental development. However, excessive or chronic ER stress in pre-eclamptic placentas leads to placental dysfunction. The precise mechanisms through which excessive ER stress impacts trophoblasts are not well understood. Here, we showed that ER stress reduces the number of lysosomes, resulting in inhibition of autophagic flux in trophoblast cells. ER stress also disrupted the translocation of lysosomes to the surface of trophoblast cells, and inhibited lysosomal exocytosis, whereby the secretion of lysosomal-associated membrane protein 1 (LAMP1) into culture media was significantly attenuated. In addition, we found that serum LAMP1 and beta-galactosidase levels were significantly decreased in pre-eclampsia patients compared to normal pregnant women, potentially indicating lysosomal dysfunction through ER stress in pre-eclamptic placentas. Thus, we demonstrated that excessive ER stress essentially disrupts homeostasis in trophoblasts in conjunction with autophagy inhibition by lysosomal impairment.

Original languageEnglish (US)
Article number11466
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • General

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