Adenine Nucleotide Catabolism in the Human Trophoblast Early and Late in Gestation

Abstract

ABSTRACT. Trophoblastic cells were separated and cul-culture, perfusion, and serial samples of newly delivered, unpertured from human first trimester and term placentae for fused placental tissue. During hypoxia placental anaerobic glystudies on energy metabolism. Changes in the catabolism colysis is activated, as evidenced by increased uptake and conof prelabeled adenine nucleotides and the adenylate energy sumption of glucose and production of lactate (2,4,(7)(8)(9)(10)(11)(12). Stores charge (EC) were followed during energy deprivation. EC of glycogen, which are present in placental tissue throughout was 0.70 f 0.04 (mean f SD) in the first trimester and pregnancy, are well preserved, when exogenous glucose can be 0.65 + 0.08 in the term cells before experiments. Both used in accelerated glycolysis (2, 7). However, substantial glycoduring hypoxia (N2-atmosphere) and in the absence of genolysis takes place during hypoxia, when availability of free glucose, ATP and EC were preserved for up to 8 h. 2-glucose is limited (5,11,13). Despite the increase in ATP Deoxyglucose caused a fall in ATP to 12.1 + 5.0 and 14.8 production through anaerobic glycolysis, tissue ATP and total + 7.4% of initial levels, and in EC to 0.46 f 0.04 and 0.42 adenine nucleotides decrease under these circumstances. The EC + 0.05 in the first trimester and term cells, respectively. also declines from the normal range of 0.70-0.81 to 0.55-0.71In first trimester cells, inhibition of oxidative phosphoryl- (2,(7)(8)(9)(12)(13)(14). ation by rotenone in the absence of glucose resulted in aThe human placenta seems able to maintain major energysignificantly slower reduction of ATP and EC than after requiring processes (lipid and steroid synthesis, amino acid acdeoxyglucose, whereas in term cells, the initial responses cumulation, etc.) and a stable carbohydrate metabolism for were similar. Of total adenine nucleotides degraded, 7.1-several hours by anaerobic glycolysis alone (2, 4, 5, 11). When 10.5% were released extracellularly as adenosine, when its activity of glycolysis is decreased, these processes are rapidly deamination was inhibited. Human trophoblast appears to impaired (5, 7). tolerate transient hypoxia or deprivation of exogenousThe effects of energy substrate deprivation on the metabolically glucose. Susceptibility to energy deprivation increases with most active part of the placenta, the trophoblast, cannot be gestational age. The main pathway for AMP-catabolism is reliably judged on the basis of the studies referred to, because deamination, but the trophoblast is able to produce aden-the trophoblast constitutes only about 13-15 % of term placental osine during accelerated adenine nucleotide catabolism. weight (15). (Pediatr Res 24: 373-379,1988) It has also been shown that acute hypoxia enhances production of vasodilatatory prostaglandins in human placenta (16), and Abbreviations that adenosine is released from perfused tissue during ischemia (17). However, blood flow autoregulation reactive to hypoxia or EC, adenylate energy char...

Increased mitochondrial damage by lipid peroxidation in trophoblast cells of preeclamptic placentas

“…West (12) has demonstrated that trophoblast from a mutant mouse with a defect in the glycolytic pathway can survive in the uterus as a anembryonic pregnancy. Trophoblast cells increase susceptibility to hypoxia and energy deprivation with gestationai age (13). These findings suggest that the mitochondrial oxidative phosphorylation in the trophoblast cells is the major source of energy supporting the placental functions.…”

Key Enzymes of Purine Degradation and Reutilization in Human Fetal Liver and Brain

“…In the human trophoblast, the deamination of AMP to IMP has been shown to dominate over its déphosphoryla tion to adenosine [Vettenranta and Raivio, 1988b], Clearly, the role of this tightly regu lated enzyme [van den Berghe et al, 1977] in the fetoplacental tissues thus cannot be eval uated by in vitro enzymological studies alone, but studies on intact cells containing physiological concentrations of all the effec tors are also required.…”

“…Therefore, the path ways of purine nucleotide metabolism in hu man fetal tissues must be further evaluated in vitro using intact cultured cells, as we have done with the trophoblast [Vettenranta, 1988;Vettenranta and Raivio, 1988b], and/or perfusion of the fetal liver.…”

“…Each of these enzymes has been stud ied in human fetal tissues [Adams and Harkness, 1976;Amano et al, 1985;Boyle et al, 1970;Fujimoto et al, 1968;Kaletha et al, 1987;Kaletha and Nowak, 1988;Stout et al, 1985], Our aim was to follow the developmental changes in the activities and kinetic charac teristics of these three enzymes in the same tissue samples from human fetuses, to gain insight into the predominant metabolic pathways and their regulation. Additionally, we wanted to compare these enzyme activi ties to those present in the metabolically most active part of the placenta, the trophoblast [Vettenranta, 1988;Vcttenranta andRaivio, 1984, 1988a, b]. [8-l4C]AMP and -hypoxanthine (50-60 mCi/ mmol) were obtained from Amersham International, UK; a,P-mcthylcnc-adcnosine 5'-diphosphatc (ADP), and 5-phosphoribosyl-l -pyrophosphate from Sigma Chemical, St. Louis, Mo., USA; cellulose thin-layer plates from Eastman Kodak, N.Y., USA; polyethyleneimine (PEI) cellulose thin-layer plates from Macherey-Nagel, FRG, and Aquasol from New England Nuclear, Mass., USA.…”