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Endoplasmic reticulum stress disrupts lysosomal homeostasis and induces blockade of autophagic flux in human trophoblasts.
Nakashima, Akitoshi; Cheng, Shi-Bin; Kusabiraki, Tae; Motomura, Kenichiro; Aoki, Aiko; Ushijima, Akemi; Ono, Yosuke; Tsuda, Sayaka; Shima, Tomoko; Yoshino, Osamu; Sago, Haruhiko; Matsumoto, Kenji; Sharma, Surendra; Saito, Shigeru.
Afiliación
  • Nakashima A; Department of Obstetrics and Gynecology, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
  • Cheng SB; Departments of Pediatrics, Women and Infants Hospital of Rhode Island, Warren Alpert Medical School of Brown University, 101 Dudley street, Providence, RI, 02905, USA.
  • Kusabiraki T; Department of Obstetrics and Gynecology, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
  • Motomura K; Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, 157-8535, Tokyo, Japan.
  • Aoki A; Department of Obstetrics and Gynecology, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
  • Ushijima A; Department of Obstetrics and Gynecology, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
  • Ono Y; Department of Obstetrics and Gynecology, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
  • Tsuda S; Department of Obstetrics and Gynecology, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
  • Shima T; Department of Obstetrics and Gynecology, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
  • Yoshino O; Department of Obstetrics and Gynecology, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
  • Sago H; Department of Obstetrics and Gynecology, Kitasato University School of Medicine, 1-15-1 Kitazato, Minami, Sagamihara, Kanagawa, 252-0374, Japan.
  • Matsumoto K; Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, 157-8535, Tokyo, Japan.
  • Sharma S; Department of Allergy and Clinical Immunology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, 157-8535, Tokyo, Japan.
  • Saito S; Department of Obstetrics and Gynecology, Kitasato University School of Medicine, 1-15-1 Kitazato, Minami, Sagamihara, Kanagawa, 252-0374, Japan.
Sci Rep ; 9(1): 11466, 2019 08 07.
Article en En | MEDLINE | ID: mdl-31391477
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Preeclampsia / Autofagia / Trofoblastos / Estrés del Retículo Endoplásmico / Lisosomas Tipo de estudio: Diagnostic_studies / Observational_studies Límite: Adult / Female / Humans / Pregnancy Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Preeclampsia / Autofagia / Trofoblastos / Estrés del Retículo Endoplásmico / Lisosomas Tipo de estudio: Diagnostic_studies / Observational_studies Límite: Adult / Female / Humans / Pregnancy Idioma: En Revista: Sci Rep Año: 2019 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido