Effects of intermittent high glucose on BeWo choriocarcinoma cells in culture

Masumoto, Akio; Takamoto, Norio; Masuyama, Hisashi; Akahori, Yasushi; Inoue, Sumito; Hiramatsu, Yuji

doi:10.1111/j.1447-0756.2011.01539.x

Cited by 6 publications

(7 citation statements)

References 36 publications

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“…High-glucose treatment tended to increase BeWo cell counts modestly in the current study setting, although Weiss et al 26 and Masumoto et al 27 both reported that trophoblast growth was inhibited by in vitro hyperglycemia. Interestingly, expression of the cellular proliferative marker KI67 was significantly dampened in high glucose, whereas another proliferative marker PCNA was unchanged, despite the modest increase in cell counts.…”

Section: Discussioncontrasting

confidence: 58%

Effects of Choline on DNA Methylation and Macronutrient Metabolic Gene Expression in in Vitro Models of Hyperglycemia

Jiang

Greenwald

Jack-Roberts

2016

Nutr Metab Insights

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Choline is an essential nutrient that plays an important role in lipid metabolism and DNA methylation. Studies in rodents suggest that choline may adversely affect glycemic control, yet studies in humans are lacking. Using the human hepatic and placental cells, HepG2 and BeWo, respectively, we examined the interaction between choline and glucose treatments. In HepG2 cells, choline supplementation (1 mM) increased global DNA methylation and DNA methyltransferase expression in both low-glucose (5 mM) and high-glucose (35 mM) conditions. Choline supplementation increased the expression of peroxisomal acyl-coenzyme A oxidase 1 (ACOX1), which mediates fatty acid β-oxidation, especially in the high-glucose condition. High-glucose exposure increased the transcription of the gluconeogenic gene phosphoenolpyruvate carboxykinase (PEPCK), while choline supplementation mitigated such increase. Compared to HepG2 cells, the placenta-derived BeWo cells were relatively unresponsive to either high-glucose or -choline treatment. In conclusion, choline and glucose interacted to affect macronutrient metabolic genes, yet there was no indication that choline may worsen glycemic control in these in vitro human cell culture models.

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Section: Discussioncontrasting

confidence: 58%

Effects of Choline on DNA Methylation and Macronutrient Metabolic Gene Expression in in Vitro Models of Hyperglycemia

Jiang

Greenwald

Jack-Roberts

2016

Nutr Metab Insights

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“…Trophoblast cell viability can be suppressed by high glucose, but the understanding about the underlying mechanisms remains limited. A previous study investigated the effects of high glucose on trophoblast BeWo cells and stated that the inhibited cell proliferation induced by high glucose might be related with dysregulation of heparin-binding-EGF (HB-EGF), which is a known survival factor for trophoblasts [ 33 , 34 ]. In another study regarding the differentially expressed miRNA in GDM, high glucose induced the upregulated miR-137 in trophoblasts, and the miR-137/PRKAA1/IL-6 axis was proposed to mediate the inhibitory effects of high glucose on trophoblast cell proliferation [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of miR-136 in Gestational Diabetes Mellitus Mediates the High-Glucose-Induced Trophoblast Cell Injury through Targeting E2F1

Zhang

Wang

Chen

et al. 2020

International Journal of Genomics

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Background. Gestational diabetes mellitus (GDM) seriously affects the health of mothers and infants. The high-glucose-induced inhibition in trophoblast cell viability is an important event in GDM pathogenesis. This study evaluated the expression and clinical significance of miR-136 in GDM patients, and the biological function and related mechanisms of miR-136 in the regulation of trophoblast cell proliferation were explored. Methods. The expression of miR-136 in serum and placenta of GDM patients was measured using quantitative Real-Time PCR. Trophoblast cells were stimulated with high-glucose medium to mimic the pathological changes of GDM, and the effect of miR-136 was examined by CCK-8 assay. A luciferase reporter assay was used to confirm the target gene of miR-136, and the relationship of E2F transcription factor 1 (E2F1) with miR-136 in GDM was further analyzed. Results. miR-136 expression was significantly elevated in GDM serum and tissue samples. By high-glucose treatment, trophoblast cell proliferation was inhibited and miR-136 expression was promoted. The knockdown of miR-136 could promote the proliferation of trophoblast cells exposed to high glucose, whereas the overexpression of miR-136 could suppress it. In addition, E2F1 was identified as a target gene of miR-136, which could mediate the regulatory effect of miR-136 on trophoblast cell proliferation. Conclusion. Collectively, miR-136 expression is increased in both serum and placental tissues in GDM patients, and miR-136 mediates the inhibiting effect of high glucose on trophoblast cell viability by targeting E2F1.

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“…Raw CT values were processed using the DCT method relative to the geometric mean of two reference genes, ACTB and GAPDH. These reference genes have been widely utilized in other studies of choriocarcinoma cell line mRNA expression levels (Lee et al, 2004;Chiu et al, 2007;Li et al, 2008;Masumoto et al, 2011;Mparmpakas et al, 2012;Chen et al, 2013). DCT values generated relative to ACTB and GAPDH were highly correlated in all assays included in this study (Supplementary data, Fig.…”

Section: Quantitative Real-time Pcrmentioning

confidence: 98%

Activation of endocrine-related gene expression in placental choriocarcinoma cell lines following DNA methylation knock-down

Hogg

Robinson

Beristain

2014

MHR: Basic Science of Reproductive Medicine

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Increasingly, placental DNA methylation is assessed as a factor in pregnancy-related complications, yet the transcriptional impact of such findings is not always clear. Using a proliferative in vitro placental model, the effect of DNA methylation loss on gene activation was evaluated at a number of genes selected for being differentially methylated in pre-eclampsia-associated placentae in vivo. We aimed to determine whether reduced DNA methylation at specific loci was associated with transcriptional changes at the corresponding gene, thus providing mechanistic underpinnings for previous clinical findings and to assess the degree of transcriptional response amongst our candidate genes. BeWo and JEG3 choriocarcinoma cells were exposed to 1 mM 5-Aza-2 ′ -deoxycytidine (5-Aza-CdR) or vehicle control for 48 h, and re-plated and cultured for a further 72 h in normal media before cells were harvested for RNA and DNA. Bisulphite pyrosequencing confirmed that DNA methylation was reduced by 30 -50% points at the selected loci studied in both cell lines. Gene activation, measured by qRT-PCR, was highly variable and transcript specific, indicating differential sensitivity to DNA methylation. Most notably, loss of DNA methylation at the leptin (LEP) promoter corresponded to a 200-fold and 40-fold increase in LEP expression in BeWo and JEG3 cells, respectively (P , 0.01). Transcripts of steroidogenic pathway enzymes CYP11A1 and HSD3B1 were up-regulated 40-fold in response to 5-Aza-CdR exposure in BeWo cells (P , 0.01). Other transcripts, including aromatase (CYP19), HSD11B2, inhibin (INHBA) and glucocorticoid receptor (NR3C1) were more moderately, although significantly, affected by loss of associated DNA methylation. These data present a mixed effect of DNA methylation changes at selected loci supporting cautionary interpretation of DNA methylation results in the absence of functional data.

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Effects of intermittent high glucose on BeWo choriocarcinoma cells in culture

Cited by 6 publications

References 36 publications

Effects of Choline on DNA Methylation and Macronutrient Metabolic Gene Expression in in Vitro Models of Hyperglycemia

Effects of Choline on DNA Methylation and Macronutrient Metabolic Gene Expression in in Vitro Models of Hyperglycemia

Differential Expression of miR-136 in Gestational Diabetes Mellitus Mediates the High-Glucose-Induced Trophoblast Cell Injury through Targeting E2F1

Activation of endocrine-related gene expression in placental choriocarcinoma cell lines following DNA methylation knock-down

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