Premium
Nuclear and cytosolic expression of placental PKM2 in preeclampsia and intrauterine growth restriction
Author(s) -
Mejia Camilo,
Bahr Brigham,
Reynolds Paul,
Arroyo Juan
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.684.9
Subject(s) - syncytiotrophoblast , placenta , pkm2 , biology , andrology , pyruvate kinase , cytotrophoblast , intrauterine growth restriction , fetus , endocrinology , medicine , glycolysis , pregnancy , metabolism , genetics
The placenta facilitates nutrient and gas exchange between the mother and the fetus. As such, placental metabolism is important for successful pregnancies. Intrauterine growth restriction (IUGR) and preeclampsia (PE) are placental pathologies that cause pre‐term delivery and disorders in neonates. Pyruvate kinase M2 (PKM2) is a metabolic enzyme expressed in embryos and cancer tissues. Our objective was to determine the cytosolic and nuclear expression of placental PKM2 protein and related signaling molecules in normal human control, PE and IUGR placentas. Placental samples were homogenized and cytoplasmic and nuclear proteins were extracted for western blot analysis. Placental tissues were also embedded for histological studies. Syncytiotrophoblast and cytotrophoblast cell lines were cultured and stained for PKM2. We observed: 1) localization of PKM2 to the villi of the human placenta; 2) increased total PKM2 expression during PE with no difference during IUGR (1.4‐fold, p<0.02); 3) elevated PKM2 nuclear expression in PE (1.65‐fold, p<0.01) and IUGR (1.5‐fold, p<0.01); 4) increased activation of ERK in PE (2.6 fold, p<0.02) and in IUGR (1.5 fold, p<0.05); 5) increased immunostaining of beta‐catenin and lactose dehydrogenase (LDH) in the villi of PE placenta; and 6) increased PKM2 nuclear expression in the invasive cytotrophoblasts cells when compared to syncytiotrophoblast cells. We conclude that PKM2 is expressed in normal, PE and IUGR placentas, but that its expression is increased in the PE placenta when compared to controls. Furthermore, our results suggest that PKM2 is a mediator of trophoblast cell invasion and its abundance influences the development of PE and IUGR. (Supported by NIH grant 7K99HD055054‐02).