Functional Proteomics: Examining the Effects of Hypoxia on the Cytotrophoblast Protein Repertoire

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• 作者：Van M. Hoang ; Russell Foulk ; Karl Clauser ; Alma Burlingame ; Bradford W. Gibson ; and Susan J. Fisher
• 刊名：Biochemistry
• 出版年：2001
• 出版时间：April 3, 2001
• 年：2001
• 卷：40
• 期：13
• 页码：4077 - 4086
• 全文大小：366K
• 年卷期：v.40,no.13(April 3, 2001)
• ISSN：1520-4995

文摘

The outcome of human pregnancy depends on the differentiation of cytotrophoblasts, specializedplacental cells that physically connect the embryo/fetus to the mother. As cytotrophoblasts differentiate,they acquire tumor-like characteristics that enable them to invade the uterus. In a novel feedback loop,the increasingly higher levels of oxygen they encounter within the uterine wall influence their differentiationinto vascular-like cells. Together, the invasive and cell surface properties of cytotrophoblasts enable themto form vascular connections with uterine blood vessels that divert maternal blood flow to the placenta,a critical hurdle in pregnancy. It is therefore important to understand how cytotrophoblasts respond tochanges in oxygen tension. Here we used a proteomics approach, two-dimensional polyacrylamide gelelectrophoresis (2-D PAGE) combined with mass spectrometry, to characterize the protein repertoire offirst trimester human cytotrophoblasts that were maintained under standard tissue culture conditions (20%O₂). 2-D PAGE showed a unique protein map as compared to placental fibroblasts and human JEG-3choriocarcinoma cells. Mass spectrometry allowed the identification of 43 spots on the cytotrophoblastmap. Enzymes involved in glycolysis and responses to oxidative stress, as well as the 14-3-3 signaling/adapter proteins, were particularly abundant. Hypoxia in vitro (2% O₂) produced discrete changes in theexpression of a subset of proteins in all the aforementioned functional categories. Together, these dataoffer new information about the early gestation cytotrophoblast protein repertoire and the generalizedmechanisms the cells use to respond to changes in oxygen tension at the maternal-fetal interface.