Arkwright P D, Rademacher T W, Dwek R A, Redman C W
Oxford Glycobiology Institute, Department of Biochemistry, United Kingdom.
J Clin Invest. 1993 Jun;91(6):2744-53. doi: 10.1172/JCI116515.
Pre-eclampsia is a placental disorder, but until now, biochemical details of dysfunction have been lacking. During an analysis of the oligosaccharide content of syncytiotrophoblast microvesicles purified from the placental chorionic villi of 10 primigravid women with proteinuric pre-eclampsia, we found an excess of glycogen breakdown products. Further investigation revealed a 10-fold increase in glycogen content (223 +/- 117 micrograms glycogen/mg protein), when compared with controls matched for gestational age at delivery (23 +/- 18 micrograms glycogen/mg protein) (P < 0.01). This was confirmed by examination of electron micrographs of chorionic villous tissue stained for glycogen. The increase in glycogen content was associated with 16 times more glycogen synthase (1,323 +/- 1,013 relative to 83 +/- 96 pmol glucose/mg protein per min) (P < 0.001), and a threefold increase in glycogen phosphorylase activity (2,280 +/- 1,360 relative to 700 +/- 540 pmol glucose/mg protein per min; P < 0.05). Similar changes in glycogen metabolism were found in trophoblast microvesicles derived from hydatidiform moles. Glycogen accumulation in villous syncytiotrophoblast may be a metabolic marker of immaturity of this cell which is unable to divide. The implications of these findings with regard to the pathogenesis of pre-eclampsia are discussed.
子痫前期是一种胎盘紊乱疾病,但直到现在,其功能障碍的生化细节仍不清楚。在对从10名患有蛋白尿性子痫前期的初产妇胎盘绒毛膜绒毛中纯化的合体滋养层微泡的寡糖含量进行分析时,我们发现糖原分解产物过多。进一步研究发现,与分娩时孕周匹配的对照组相比,糖原含量增加了10倍(223±117微克糖原/毫克蛋白质)(对照组为23±18微克糖原/毫克蛋白质)(P<0.01)。对绒毛膜绒毛组织糖原染色的电子显微镜检查证实了这一点。糖原含量的增加与糖原合酶增加16倍有关(相对于每分钟83±96皮摩尔葡萄糖/毫克蛋白质,为1323±1013)(P<0.001),糖原磷酸化酶活性增加了三倍(相对于每分钟700±540皮摩尔葡萄糖/毫克蛋白质,为2280±1360;P<0.05)。在葡萄胎来源的滋养层微泡中也发现了糖原代谢的类似变化。绒毛合体滋养层中的糖原积累可能是这种无法分裂的细胞不成熟的代谢标志物。本文讨论了这些发现对子痫前期发病机制的意义。