The effect of hypoxia on human trophoblast in culture: Morphology, glucose transport and metabolism

Esterman, Abbie L.; Greco, M. Alba; Mitani, Yasuo; Finlay, Thomas H.; Ismail‐Beigi, Faramarz; Dancis, Joseph

doi:10.1016/s0143-4004(97)90084-9

Cited by 94 publications

(53 citation statements)

References 27 publications

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“…In this report, EPO-R, a recognized marker of hypoxia, increased in the high altitude syncytial membranes, as predicted from cellular studies. However, both nutrient transporters (TfR and GLUT1), in contrast to what is observed in vitro [7,9,10,12] showed decreased protein expression. The reduction in basal membrane GLUT1 is especially noteworthy, as the basal membrane is the rate-limiting step in transplacental glucose transfer [18].…”

Section: Discussioncontrasting

confidence: 61%

“…None of these systems are capable of determining the systemic effects of hypoxia on placental function and thus, while valuable for their insights into cellular and tissue responses to hypoxia, cannot provide information on the long-term developmental effects of chronically reduced maternal/placental pO 2 . Nonetheless, based on prior studies in vitro showing increase in GLUT1 [7], and decrease in the system A amino acid transporters in hypoxia [8], we hypothesized that chronic hypoxia might alter nutrient delivery to the fetus via changes in the expression of placental nutrient transporters. In this report we describe the effect of a reduction in maternal PaO 2 in vivo on the expression of the GLUT1 glucose transporters on syncytial microvillous and basal membranes of placentas from high (3100 m) versus low altitude (1600 m).…”

Section: Introductionmentioning

confidence: 99%

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Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters

2006

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Birth weight is reduced and the risk of preeclampsia is increased in human high altitude pregnancies. There has been little work to determine whether hypoxia acts directly to reduce fetal growth (e.g. reduced blood flow and oxygen delivery), or via changes in functional capacities such as nutrient transport. We therefore investigated the expression of a primary nutrient transporter, the GLUT1 glucose transporter and two in vitro markers of hypoxia (erythropoietin receptor, EPO-R, and transferrin receptor, TfR) in the syncytial microvillous (MVM) and basal membrane fractions (BMF) of 13 high (3100 m) and 12 low (1600 m) altitude placentas from normal term pregnancies. Birth weight was lower at 3100 m than at 1600 m despite similar gestational age, but none of the infants were clinically designated as fetal growth restriction. EPO-R, TfR and GLUT1 were examined by immunoblotting and maternal circulating erythropoietin and transferrin by ELISA. EPO-R was greater on the MVM (C75%) and BMF (C25%) at 3100 m. TfR was 32% lower on the MVM at 3100 m. GLUT1 was 40% lower in the BMF at 3100 m. Circulating EPO was greater at high altitude, while transferrin was similar, and neither correlated with their membrane receptors. BMF GLUT1 was positively correlated with birth weight at high, but not low altitude. In this in vivo model of chronic placental hypoxia, syncytial EPO-R increased as expected, while nutrient transporters decreased, opposite to what has been observed in vitro. Therefore, hypoxia acts to reduce fetal growth not simply by reducing oxygen delivery, but also by decreasing the density of nutrient transporters.

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Section: Discussioncontrasting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters

2006

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“…Thus, a variety of pathophysiological conditions during pregnancy are accompanied by hypoxia (10,34,37). It was shown by Esterman et al that in vitro cultures of trophoblasts can survive extreme hypoxia and that they react rapidly to restitution of normal oxygen tension by readopting their reduced metabolism and cell cycle (38). This is in line with the data from the present study.…”

Section: Discussionsupporting

confidence: 93%

Hypoxia-induced leptin production in human trophoblasts does not protect from apoptosis

et al. 2005

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Objective: The ob-gene product, leptin, is an important regulator of placental and fetal development during pregnancy. Leptin, being induced by hypoxia in the placenta, is a known pro-apoptotic molecule in adipose tissue but is also known to inhibit apoptosis in other tissues like neuroblastoma cells. Based on these findings, we investigated if leptin has a pro-or anti-apoptotic effect on a trophoblastic cell line (JAr cells) in the presence or absence of oxygen. Methods and results: Measurement of leptin in the supernatant by using ELISA showed hypoxiainduced leptin production in JAr cells in vitro. This could be confirmed by a leptin-specific RT-PCR. By analyzing leptin and/or hypoxia exposed cells with FACS cytometry we found that JAr cells can cope with hypoxia down to oxygen tensions of 1%. At this level, only a small number of cells underwent apoptosis. Interestingly, leptin added to the culture medium in high concentrations was not able to interfere with the rate of proliferation or apoptosis in these cells independent of the oxygen tension. Finally, an anti-caspase-3 and anti-caspase-9 Western blot was performed. Again, no difference in the expression of caspase-3 and -9 under the conditions tested was seen. Conclusions: These results show that leptin, produced by placental cells after hypoxia in vitro, has no influence on the rate of proliferation of these cells. Furthermore, it does not influence apoptotic pathways in the trophoblastic cell line tested under hypoxic and non-hypoxic conditions. European Journal of Endocrinology 153 455-461

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“…This work suggests that nuclear factors Sp1/Sp3 may mediate the transcriptional activation of GLUT3 along with MSY-1 during neurodevelopment; whereas phosphorylated cAMP regulatory element-binding (pCREB) protein may regulate transactivation of GLUT3 expression during neurotransmission under conditions of substrate deficiency (104). Furthermore, posttranscriptional regulation of GLUT3 protein expression occurs in term placenta, suggesting a tight regulation of expression dependent on environmental conditions in the developing placenta (33). In the preimplantation embryo, a pulse of glucose or glucosamine for 1-2 h prior to compaction is necessary to induce expression of GLUT3 and thus to progress through normal development (101).…”

Section: Glut3: What Is In the Futurementioning

confidence: 97%

“…This developmental differential expression of GLUT3 protein and constant expression of GLUT3 mRNA at term suggests some form of active regulation that suppresses expression of the protein. Studies have demonstrated that this level of mRNA in term human trophoblast is regulated by hypoxia, suggesting that a constitutive block in translation of the mRNA does exist (33).…”

Section: Glut3 In the Embryomentioning

confidence: 99%

The facilitative glucose transporter GLUT3: 20 years of distinction

Simpson

Dwyer

Malide

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

403

322

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Glucose metabolism is vital to most mammalian cells, and the passage of glucose across cell membranes is facilitated by a family of integral membrane transporter proteins, the GLUTs. There are currently 14 members of the SLC2 family of GLUTs, several of which have been the focus of this series of reviews. The subject of the present review is GLUT3, which, as implied by its name, was the third glucose transporter to be cloned (Kayano T, Fukumoto H, Eddy RL, Fan YS, Byers MG, Shows TB, Bell GI. J Biol Chem 263: [15245][15246][15247][15248] 1988) and was originally designated as the neuronal GLUT. The overriding question that drove the early work on GLUT3 was why would neurons need a separate glucose transporter isoform? What is it about GLUT3 that specifically suits the needs of the highly metabolic and oxidative neuron with its high glucose demand? More recently, GLUT3 has been studied in other cell types with quite specific requirements for glucose, including sperm, preimplantation embryos, circulating white blood cells, and an array of carcinoma cell lines. The last are sufficiently varied and numerous to warrant a review of their own and will not be discussed here. However, for each of these cases, the same questions apply. Thus, the objective of this review is to discuss the properties and tissue and cellular localization of GLUT3 as well as the features of expression, function, and regulation that distinguish it from the rest of its family and make it uniquely suited as the mediator of glucose delivery to these specific cells.neurons; sperm; preimplantation embryo; white blood cells GLUCOSE METABOLISM IS VITAL to most mammalian cells, and the passage of glucose across cell membranes is facilitated by a family of integral membrane transporter proteins, the GLUTs. There are currently 14 members of the SLC2 family of GLUTs, several of which have been the focus of this series of reviews. The subject of the present review is GLUT3 which, as implied by its name, was the third glucose transporter to be cloned (62) and was originally designated as the neuronal glucose transporter. Together with GLUT1, -2, and -4, it comprises the Class 1 group of transporters (For review see Refs. 15,81,121). With the cloning of GLUT3, it became apparent that the brain did not rely exclusively on GLUT1 and that GLUT3 was highly and specifically expressed by neurons. Thus, GLUT3 became the third facilitative glucose transporter isoform with unique characteristics suited for cell-specific expression and function. GLUT2 is ideally suited for expression in liver and pancreas due to its high K m for glucose; GLUT4 and its translocation from intracellular vesicles to the cell surface facilitates insulin-stimulated glucose uptake in insulin-sensitive cells: muscle and fat. The overriding question that drove the early work in GLUT3 in the brain was: why would neurons need a separate glucose transporter isoform; what is it about GLUT3 that specifically suits the needs of the highly metabolic and oxidative neuron with its high glucose demand?...

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The effect of hypoxia on human trophoblast in culture: Morphology, glucose transport and metabolism

Cited by 94 publications

References 27 publications

Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters

Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters

Hypoxia-induced leptin production in human trophoblasts does not protect from apoptosis

The facilitative glucose transporter GLUT3: 20 years of distinction

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