Depto. de Fisiología y Biofísica, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Casilla 70005, Santiago 7, Chile.
J Membr Biol. 2011 Jun;241(3):127-40. doi: 10.1007/s00232-011-9369-3. Epub 2011 May 15.
Intrauterine growth restriction (IUGR) and preeclampsia (PE) are leading causes of perinatal and maternal morbidity and mortality. Previously we reported the expression of lipid rafts in classical microvillous membrane (MVM) and light microvillous membrane (LMVM), two subdomains in apical membrane from the human placental syncytiotrophoblast (hSTB), which constitute the epithelium responsible for maternal-fetal transport. Here the aim was to study the raft and cytoskeletal proteins from PE and IUGR. Microdomains from MVM and LMVM were tested with raft markers (placental alkaline phosphatase, lipid ganglioside, and annexin 2) and a nonraft marker (hTf-R). No changes were detected with those markers in whole purified apical membranes in normal, PE, and IUGR pregnancies; however, their patterns of distribution in lipid rafts were different in PE and IUGR. Cholesterol depletion modified their segregation, confirming their presence in lipid rafts, although unlike normal placenta, in these pathologies there is only one type of microdomain. Additionally, the cytoskeleton proteins actin, ezrin, and cytokeratin-7 showed clear differences between normal and pathological membranes. Cytokeratin-7 expression decreased to 50% in PE, and the distribution between LMVM and MVM (43 and 57%, respectively) changed in both PE and IUGR, in contrast with the asymmetrical enrichment obtained in normal LMVM (62%). In conclusion, lipid rafts from IUGR and PE have different features compared to rafts from normal placentae, and this is associated with alterations in the expression and distribution of cytoskeletal proteins.
胎儿宫内生长受限（IUGR）和子痫前期（PE）是围产期和孕产妇发病率和死亡率的主要原因。我们之前报道了脂质筏在经典微绒毛膜（MVM）和轻微绒毛膜（LMVM）中的表达，这两种亚域位于人胎盘合体滋养层（hSTB）的顶膜中，是负责母体-胎儿转运的上皮的组成部分。这里的目的是研究 PE 和 IUGR 中的筏和细胞骨架蛋白。用筏标记物（胎盘碱性磷酸酶、脂质神经节苷脂和膜联蛋白 2）和非筏标记物（hTf-R）测试 MVM 和 LMVM 的微域。在正常、PE 和 IUGR 妊娠的整个纯化顶膜中，这些标记物没有检测到变化；然而，它们在 PE 和 IUGR 中的分布模式不同。胆固醇耗竭改变了它们的分离，证实了它们在脂质筏中的存在，尽管与正常胎盘不同，在这些病理中只有一种类型的微域。此外，细胞骨架蛋白肌动蛋白、埃兹蛋白和细胞角蛋白-7在正常和病理膜之间表现出明显的差异。PE 中细胞角蛋白-7的表达下降到 50%，并且在 LMVM 和 MVM 之间的分布（分别约为 43%和 57%）在 PE 和 IUGR 中都发生了变化，与正常 LMVM 中获得的不对称富集（约 62%）形成对比。总之，与正常胎盘的筏相比，IUGR 和 PE 的脂质筏具有不同的特征，这与细胞骨架蛋白的表达和分布改变有关。
