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Molecular Mechanisms Linking Amino Acid (Leucine) Deprivation To Igfbp-1 Hyperphosphorylation In Fetal Growth Restriction, Niyati M. Malkani

Electronic Thesis and Dissertation Repository

In this study, we explore the molecular mechanisms linking amino acid (leucine) deprivation to IGFBP-1 hyperphosphorylation in vitro. During pregnancy, a maladaptive fetal response to in utero amino acid deprivation leads to Fetal Growth Restriction (FGR). FGR infants display elevated phosphorylated IGFBP-1, which is associated with decreased IGF-I bioavailability. Leucine deprivation inhibits mechanistic target of rapamycin (mTOR) signaling and stimulates the amino acid response (AAR). Using HepG2 cells, a model for fetal hepatocytes, we demonstrate that in leucine deprivation, the AAR modulates total and phosphorylated IGFBP-1 while mTOR mediates total IGFBP-1 secretion only. We also reveal that protein kinases …