G T Lee1, M D Price2, C A Mejia2, H L Galan3, J A Arroyo4. 1. Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS, USA. 2. Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, USA. 3. Department of Obstetrics and Gynaecology, University of Colorado Denver and Health Sciences Center, Aurora, CO, USA. 4. Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT, USA. Electronic address: jarroyo@byu.edu.
Abstract
OBJECTIVES: To assess the concentrations of inositol and sorbitol, and determine the expression of related osmolyte factors [nuclear factor of activated T cells 5, also known as tonicity responsive binding protein (NFAT5/TonEBP); sodium myo-inositol transporter (SLC5A3); and aldose reductase] in placentas of pre-eclamptic (PE) patients and trophoblast BeWo cells subjected to hypertonic stress in vitro. STUDY DESIGN: Control and PE placentas were collected. BeWo cells were cultured and subjected to a hyperosmolar solution for 4h. Western blot analysis was performed on NFAT5, SLC5A3, aldose reductase and ERK proteins. High-performance liquid chromatography was used to determine the levels of inositol and sorbitol in cell lysates. RESULTS: Compared with control placentas, PE placentas showed higher levels of inositol and NFAT5, and lower levels of SLC5A3. Treated BeWo cells showed higher levels of inositol, sorbitol, NFAT5 total protein, SLC5A3 and aldose reductase, and increased ERK activation compared with control BeWo cells. CONCLUSIONS: Hyperosmolar conditions increase the expression of NFAT5 in PE placentas and BeWo cells, and may account for the increased osmolyte levels. NFAT5 may accomplish this through aldose reductase and SLC5A3 in trophoblast cells.
OBJECTIVES: To assess the concentrations of inositol and sorbitol, and determine the expression of related osmolyte factors [nuclear factor of activated T cells 5, also known as tonicity responsive binding protein (NFAT5/TonEBP); sodium myo-inositol transporter (SLC5A3); and aldose reductase] in placentas of pre-eclamptic (PE) patients and trophoblast BeWo cells subjected to hypertonic stress in vitro. STUDY DESIGN: Control and PE placentas were collected. BeWo cells were cultured and subjected to a hyperosmolar solution for 4h. Western blot analysis was performed on NFAT5, SLC5A3, aldose reductase and ERK proteins. High-performance liquid chromatography was used to determine the levels of inositol and sorbitol in cell lysates. RESULTS: Compared with control placentas, PE placentas showed higher levels of inositol and NFAT5, and lower levels of SLC5A3. Treated BeWo cells showed higher levels of inositol, sorbitol, NFAT5 total protein, SLC5A3 and aldose reductase, and increased ERK activation compared with control BeWo cells. CONCLUSIONS: Hyperosmolar conditions increase the expression of NFAT5 in PE placentas and BeWo cells, and may account for the increased osmolyte levels. NFAT5 may accomplish this through aldose reductase and SLC5A3 in trophoblast cells.
Authors: Jeremy A Sandgren; Guorui Deng; Danny W Linggonegoro; Sabrina M Scroggins; Katherine J Perschbacher; Anand R Nair; Taryn E Nishimura; Shao Yang Zhang; Larry N Agbor; Jing Wu; Henry L Keen; Meghan C Naber; Nicole A Pearson; Kathy A Zimmerman; Robert M Weiss; Noelle C Bowdler; Yuriy M Usachev; Donna A Santillan; Matthew J Potthoff; Gary L Pierce; Katherine N Gibson-Corley; Curt D Sigmund; Mark K Santillan; Justin L Grobe Journal: JCI Insight Date: 2018-10-04
Authors: Juan F Mejia; Kelsey M Hirschi; Kary Y F Tsai; Matthew G Long; Benton C Tullis; Eliza E K Bitter; Benjamin T Bikman; Paul R Reynolds; Juan A Arroyo Journal: Reprod Biol Endocrinol Date: 2019-10-23 Impact factor: 5.211