Cell Invasion, Placenta, PKM2, Trophoblast
The Pyruvate kinase isozymes M2 (PKM2) protein is a metabolic enzyme that regulates the final step of glycolysis. This enzyme is present in highly proliferating cells such as those present in embryonic tissues, cancer and in the placental trophoblast. We recently studied PKM2 protein in the human placenta at term. Our results demonstrated upregulated placental PKM2 during preeclampsia (PE) where trophoblast invasion is decreased and hypoxia is present. Our objective was to determine the cytosolic and nuclear PKM2 expression pattern and determine PKM2 regulation of trophoblast cell invasion. Trophoblast cells were cultured in normoxic and hypoxic conditions and real time cell invasion was determined during activation (Fructose-6-bisphosphate) or inhibition (Shikonin) of PKM2. Treated cells were lysed for western blot analysis of PKM2. During normoxia, we observed: 1) 2-fold increase (p<0.002) in trophoblast invasion when PKM2 was activated; 2) a 68-fold reduction (p<0.002) in trophoblast invasion when PKM2 activation was inhibited; 3) a 1.4-fold induction (p<0.03) of nuclear PKM2 in the trophoblast when PKM2 was activated; 4) a 1.6-fold induction (p<0.04) of nuclear PKM2 after PKM2 inactivation; and 5) a 1.4-fold decrease (p<0.03) in cytosolic PKM2 after PKM2 inactivation. During hypoxia we observed: 1) decreased cell invasion (~3.0-fold; p<0.005) in treated cells; 2) decreased cytosolic PKM2 expression (~1.6-fold; p<0.03) in treated cells; and 3) no significant differences in the expression of cytosolic PKM2. We conclude that PKM2 regulates trophoblast cell invasion depending of its cellular localization. Furthermore, our results suggest that PKM2 regulation is affected by hypoxia. These results suggest that PKM2 could be a mediator of trophoblast cell invasion and its abundance influences the development of complicated pregnancies like PE.
BYU ScholarsArchive Citation
Mejia, Juan; Hall, Parker; Hirschi, Kelsey; Reynolds, Paul R.; and Arroyo, Juan, "Regulation of Trophoblast Invasion by Pyruvate Kinase Isozyme M2 (PKM2)" (2018). All Student Publications. 234.
Physiology and Developmental Biology
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