eNOS/iNOS and endoplasmic reticulum stress-induced apoptosis in the placentas of patients with preeclampsia

J Hum Hypertens. 2017 Jan;31(1):49-55. doi: 10.1038/jhh.2016.17. Epub 2016 Mar 31.

Abstract

Disruption of nitric oxide pathway and endoplasmic reticulum (ER) stress had been observed in preeclampsia (PE). However, the correlation and overall detailed expression profiles of ER stress-related markers and endothelial nitric oxide synthase/inducible nitric oxide synthase (eNOS/iNOS) in patients with PE were poorly understood. In this study, placental protein expression of ER stress-related markers as well as eNOS/iNOS in normotensive control (n=32) and PE pregnancies (n=32) was examined by western blot. In addition, apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick-end labelling (TUNEL) staining in placentas. Compared with control, we found elevated ER stress response was agreeable with iNOS upregulation in placenta tissue of PE patients. Placental protein expression of ER stress-related markers, including GRP78, GRP94, p-PERK, eIF2a, p-eIF2a, XBP1, CHOP, Ire1, p-Ire1 and iNOS, was higher, and eNOS expression was lower in PE (P<0.05 for all); however, the expression of ATF6 and PERK was similar in the PE and control groups. Upregulation of CHOP and iNOS was consistent of apoptosis increasing indicated by TUNEL staining and caspase 4 expression upregulation in PE placenta. Our datas suggest that the exaggerated ER stress response and upregulated iNOS are probably associated with increased apoptosis in placenta of PE patients and may contribute to the pathophysiology of PE.

MeSH terms

  • Adult
  • Apoptosis
  • Case-Control Studies
  • Caspases, Initiator / metabolism
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress*
  • Female
  • Humans
  • Nitric Oxide Synthase Type II / metabolism*
  • Nitric Oxide Synthase Type III / metabolism*
  • Placenta / metabolism*
  • Pre-Eclampsia / metabolism*
  • Pregnancy
  • Trophoblasts

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • NOS2 protein, human
  • NOS3 protein, human
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • CASP4 protein, human
  • Caspases, Initiator