title: AMPK knockdown in placental trophoblast cells results in altered morphology and function.
abstract: The placenta is a transient organ that develops upon the initiation of pregnancy and is essential for embryonic development and fetal survival. The rodent placenta consists of distinct lineages and includes cell types that are analogous to those that make up the human placenta. Trophoblast cells within the labyrinth layer, which lies closest to the fetus, fuse and come in contact with maternal blood, thus facilitating nutrient and waste exchange between the mother and the baby. Abnormalities of the placenta may occur as a result of cellular stress and have been associated with pregnancy-associated disorders: such as preeclampsia, intrauterine growth restriction, and placental insufficiency. Cellular stress has also been shown to alter proliferation and differentiation rates of trophoblast cells. This stress response is important for cell survival and ensures continued placental functionality. AMP-activated protein kinase is an important sensor of cellular metabolism and stress. To study the role of AMPK in the trophoblast cells, we used RNA interference to simultaneously knockdown levels of both the AMPK alpha isoforms, AMPKα1 and AMPKα2. SM10 trophoblast progenitor cells were transduced with AMPKα1/2 shRNA and stable clones were established to analyze the effects of AMPK knockdown on important cellular functions. Our results indicate that a reduction in AMPK levels causes alterations in cell morphology, growth rate, and nutrient transport, thus identifying an important role for AMPK in the regulation of placental trophoblast differentiation.
authors.affiliation: 1 Program in Microbiology and Immunology, Department of Neuroscience, Cell Biology and Physiology, Wright State University Boonshoft School of Medicine , Dayton, Ohio.
authors.forename: Erica A K
authors.initials: EA
authors.lastname: Carey
authors.forename: Renee E
authors.initials: RE
authors.lastname: Albers
authors.forename: Savannah R
authors.initials: SR
authors.lastname: Doliboa
authors.forename: Martha
authors.initials: M
authors.lastname: Hughes
authors.forename: Christopher N
authors.initials: CN
authors.lastname: Wyatt
authors.forename: David R C
authors.initials: DR
authors.lastname: Natale
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Brown
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D051379:Mice; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology*; D014327:Trophoblasts / Q000166:cytology / Q000201:enzymology*
chemical_list: C548179:Prkaa1 protein, mouse; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases