Mitochondria from human term placenta. II. Characterization of respiratory pathways and coupling mechanisms

Olivera, Arturo A.; Meigs, Robert A.

doi:10.1016/0005-2728(75)90165-6

Cited by 20 publications

(4 citation statements)

References 23 publications

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“…The absence of apoptosis in the trophoblast models could suggest the presence of some unknown pro-survival factors, a defect in the apoptosis induction machinery or the absence of increased generation of reactive oxygen species. In the term trophoblast a large proportion of the mitochondria is uncoupled [42]. Mitochondrial activity in the presence of hyperglycaemia was depressed in JAR and JEG-3 cells and this was not the result of oxidative stress because the antioxidant N-acetylcysteine did not lessen or abrogate the hyperglycaemia-induced alteration in mitochondrial activity.…”

Section: Discussionmentioning

confidence: 94%

Hyperglycaemia in vitro alters the proliferation and mitochondrial activity of the choriocarcinoma cell lines BeWo, JAR and JEG-3 as models for human first-trimester trophoblast

Weiß¹,

Červar²,

Puerstner³

et al. 2001

Diabetologia

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Despite considerable advances in the treatment of diabetes in the past decades, diabetic pregnancies can still be associated with fetal growth disturbances even when an optimized and intensive metabolic control has been achieved. Macrosomia of the fetus is a common and well-known consequence of maternal diabetes with an increased obstetric risk. The increase in fetal fat mass that accounts for the fetal overweight [1] is the result of fetal hyperinsulinism as a consequence of maternal and, therefore, fetal hyperglycaemia [2]. According to the dynamics of fetal growth, macrosomia is caused by metabolic alterations or hyperglycaemic insults predominantly in later stages of pregnancy [3,4]. In contrast diabetes-associated metabolic derangements in the first trimester of pregnancy can lead to malformations [5] and to delayed growth of the developing embryo [6,7]. Whereas the molecular mechanisms underlying embryo malformations have received enormous attention, no data are available to explain early fetal growth delay. Because of the close link between placental and fetal growth, early intrauterine growth delay could be caused by a reduced growth of the pla- Diabetologia (2001) Abstract Aims/hypothesis. Early intrauterine growth delay in diabetes could be caused by a reduced growth of the placenta. Our study investigates whether hyperglycaemia in vitro reduces trophoblast proliferation. Methods. First-trimester trophoblast cell models (BeWo, JAR and JEG-3 choriocarcinoma cells) were cultured for 24 and 48 h with 5.5 mmol/l d-glucose, 25 mmol/l d-glucose (hyperglycaemia) and with an osmotic control. Cell number, total protein and nucleic acid content and mitochondrial activity (tetrazolium salt assay) were measured, the cell cycle analysed (FACS, cyclin B1 levels) and apoptosis (Annexin-V) measured.Results. In BeWo cells hyperglycaemia reduced cell number, protein, nucleic acid and cyclin B1 levels. The reduced G 2 /M and increased G 0 /G 1 population after 24 h reflects growth arrest at G 0 /G 1 . In JAR cells after 24 h the population was arrested in G 0 /G 1 , whereas after 48 h the G 0 /G 1 block was abrogated and the cells were arrested at G 2 /M. The net effect was an unchanged cell number. In JEG-3 cells hyperglycaemia resulted in fewer cells after 24 h but not after 48 h indicating some adaptation. Mitochondrial activity was either stimulated (BeWo) or reduced (JAR, JEG-3) under hyperglycaemia. Some of these effects were also induced by hyperosmolarity alone. Conclusion/interpretation. Hyperglycaemia has the potential to inhibit the proliferation of first-trimester trophoblast cell models. The mechanisms leading to growth arrest and to changes in mitochondrial activity are complex and depend on differentiation. We hypothesise a hyperglycaemia-induced impairment of placental growth in the first trimester of a poorly controlled diabetic pregnancy. [Diabetologia (2001) 44: 209±219]

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Section: Discussionmentioning

confidence: 94%

Hyperglycaemia in vitro alters the proliferation and mitochondrial activity of the choriocarcinoma cell lines BeWo, JAR and JEG-3 as models for human first-trimester trophoblast

Weiß¹,

Červar²,

Puerstner³

et al. 2001

Diabetologia

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“…However, no changes in either uterine or umbilical alanine uptakes were noted. Alternatively, fetal hyperglycemia may have caused a significant shift away from the use of glucose as a placental fuel in favor of other potential placental substrates (36).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Chronic Fetal Hyperglycemia on Substrate Uptake by the Ovine Fetus and Conceptus

et al. 1985

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ABSTRACT. Hyperglycemia in fetal sheep has been shown to increase the fetal metabolic rate. Fetal venous glucose infusion was performed in eight late gestation, chronically catheterized fetal lambs to assess any changes in substrate uptake by the ovine uterus and conceptus. Fetal glucose infusion (1 1.9 f 0.6 mg glucose. kg-'. min-') caused a stable increase in fetal plasma glucose concentration approximately 3-fold above baseline. The fetal glucose entry rate increased from 6.6 f 0.7 to 9.3 f 0.6 mg.kg-'. min-' by day 3 of infusion (p < 0.01) despite a net umbilical glucose excretion during the period of fetal hyperglycemia. Due to a concomitant increase in fetal oxygen consumption, no change in fetal glucose/02 quotient was observed. A significant relationship was noted (p < 0.02) between the fetal glucose entry rate and the rate of fetal oxygen consumption. Fetal glucose infusion caused a decrease in uterine glucose uptake as well. No changes were observed in calculated net placental glucose uptake although the relative fetal contribution increased from net placental exit to fetus to a placental uptake amounting to 20.8 f 5.8% of the total placental glucose uptake ( p < 0.01). Although no changes in fetal lactate concentration occurred, both maternal and fetal lactate entry rates increased, the magnitude of increase being significantly related to fetal glucose concentration. Both maternal and fetal insulin concentrations rose during the period of fetal hyperglycemia and were related to the respective increases of maternal or fetal substrate uptakes but not to fetal oxygen consumption. These studies suggest that glucose induces significant stimulation of fetal oxidative metabolism and that fuel needs during this period are met by accelerated fetal glucose entry as well as accelerated placental production of lactate. Superimposed hypoxemia during these circumstances might be expected to have a greater effect on fetal oxygenation and pH than during normoxemic circumstances. (Pediatr Res 19: 659-666, 1985) Abbreviations f, umbilical blood flow (ml. kg-'. min-') F, uterine blood flow (ml -min-') glu, glucose concentration (mgldl) lac, lactate concentration (mM) ala, alanine concentration (mM) Common abnormalities in human infants of diabetic mothers include gross fetal macrosomia and visceromegaly with attendant postnatal hyperinsulinemia and hypoglycemia (1, 2). Autopsied infants of diabetic mothers have shown evidence of significant pancreatic islet hyperplasia (3,4) to support the hypothesis that excesses in maternal-fetal ducose transfer are responsible for fetal pancreatic islet stimulation and subsequent signs of fetal insulin excess. However, some features shared by fetuses of severely diabetic mothers such as an increased late stillborn rate and a poor ability to tolerate labor have not been adequately explained by the mechanism of excessive substrate transfer. Previous information obtained from chronically catheterized fetal sheep has suggested that fetal glucose infusion is associated with stimulation...

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“…Using GPD2 KO mice, it was further shown that sperm capacitation requires GPD2 activity for ROS generation in spermatozoa 107 . The placenta has disproportionately higher GPD2 levels among mitochondrial respiratory enzymes than other tissues 108 , 109 and exhibits high GPD2-dependent generation of hydrogen peroxide (H 2 O 2 ) 110 , the physiological meaning of which is not clear at this point. More relevant to pathological conditions is probably the role of GPD2-mediated ROS in ischemia‒reperfusion injury (IRI), where resumed blood flow after blood vessel blockage induces paradoxical tissue damage 111 .…”

Section: Glycerol 3-phosphate Dehydrogenases: Individual Enzymes and ...mentioning

confidence: 99%

Glycerol 3-phosphate dehydrogenases (1 and 2) in cancer and other diseases

Oh,

Mai,

Kim

et al. 2024

Exp Mol Med

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The glycerol 3-phosphate shuttle (GPS) is composed of two different enzymes: cytosolic NAD+-linked glycerol 3-phosphate dehydrogenase 1 (GPD1) and mitochondrial FAD-linked glycerol 3-phosphate dehydrogenase 2 (GPD2). These two enzymes work together to act as an NADH shuttle for mitochondrial bioenergetics and function as an important bridge between glucose and lipid metabolism. Since these genes were discovered in the 1960s, their abnormal expression has been described in various metabolic diseases and tumors. Nevertheless, it took a long time until scientists could investigate the causal relationship of these enzymes in those pathophysiological conditions. To date, numerous studies have explored the involvement and mechanisms of GPD1 and GPD2 in cancer and other diseases, encompassing reports of controversial and non-conventional mechanisms. In this review, we summarize and update current knowledge regarding the functions and effects of GPS to provide an overview of how the enzymes influence disease conditions. The potential and challenges of developing therapeutic strategies targeting these enzymes are also discussed.

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Mitochondria from human term placenta. II. Characterization of respiratory pathways and coupling mechanisms

Cited by 20 publications

References 23 publications

Hyperglycaemia in vitro alters the proliferation and mitochondrial activity of the choriocarcinoma cell lines BeWo, JAR and JEG-3 as models for human first-trimester trophoblast

Hyperglycaemia in vitro alters the proliferation and mitochondrial activity of the choriocarcinoma cell lines BeWo, JAR and JEG-3 as models for human first-trimester trophoblast

The Effects of Chronic Fetal Hyperglycemia on Substrate Uptake by the Ovine Fetus and Conceptus

Glycerol 3-phosphate dehydrogenases (1 and 2) in cancer and other diseases

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