Activation of adenosine A2B receptor impairs properties of trophoblast cells and involves mitogen-activated protein (MAP) kinase signaling

Darashchonak, Natallia; Sarisin, Akin; Kleppa, Marc-Jens; Powers, Robert W.; Versen‐Höynck, Frauke von

doi:10.1016/j.placenta.2014.06.369

Cited by 15 publications

(13 citation statements)

References 36 publications

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“…ADORA2B, encoding the Adenosine A2B receptor, was shown to play a role in placental development and possibly in the pathophysiology of hypoxia and preeclampsia (PE) in pregnant women (Acurio et al, 2014;Darashchonak et al, 2014;Jia et al, 2012), a pathology which has also been associated with air pollution exposure during pregnancy (M. Pedersen et al, 2014). In both mice and humans, it has been demonstrated that activation of ADORA2B signalling contributes to the pathogenesis of PE (Huang et al, 2017), to small foetuses, small placentas and foetal growth restriction (Iriyama et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Pregnancy exposure to atmospheric pollution and meteorological conditions and placental DNA methylation

Abraham

Rousseaux

Agier

et al. 2018

Environment International

107

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The methylation of ADORA2B, a gene whose expression was previously associated with hypoxia and pre-eclampsia, was consistently found here sensitive to atmospheric pollutants. In addition, air pollutants were associated to DMRs pointing towards genes previously implicated in preeclampsia, hypertensive and metabolic disorders. These findings demonstrate that air pollutants exposure at levels commonly experienced in the European population are associated with placental gene methylation and provide some mechanistic insight into some of the reported effects of air pollutants on preeclampsia.

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Section: Discussionmentioning

confidence: 99%

Pregnancy exposure to atmospheric pollution and meteorological conditions and placental DNA methylation

Abraham

Rousseaux

Agier

et al. 2018

Environment International

107

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“…It is well known that migration activity is a very important factor contributing to the implantation of trophoblasts into the maternal myometrium layer, and that hypoxia induces migration activity in trophoblasts through the activation of several signal molecules and adhesion molecules [ 15 16 17 ]. Therefore, we investigated whether selenium could control the migration of trophoblast cells.…”

Section: Resultsmentioning

confidence: 99%

Effects of selenium on the survival and invasion of trophoblasts

Na¹,

Seok

Park

et al. 2018

Clin Exp Reprod Med

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ObjectivePlacental oxidative stress is known to be a factor that contributes to pregnancy failure. The aim of this study was to determine whether selenium could induce antioxidant gene expression and regulate invasive activity and mitochondrial activity in trophoblasts, which are a major cell type of the placenta.MethodsTo understand the effects of selenium on trophoblast cells exposed to hypoxia, the viability and invasive activity of trophoblasts were analyzed. The expression of antioxidant enzymes was assessed by reverse-transcription polymerase chain reaction. In addition, the effects of selenium treatment on mitochondrial activity were evaluated in terms of adenosine triphosphate production, mitochondrial membrane potential, and reactive oxygen species levels.ResultsSelenium showed positive effects on the viability and migration activity of trophoblast cells when exposed to hypoxia. Interestingly, the increased heme oxygenase 1 expression under hypoxic conditions was decreased by selenium treatment, whereas superoxide dismutase expression was increased in trophoblast cells by selenium treatment for 72 hours, regardless of hypoxia. Selenium-treated trophoblast cells showed increased mitochondrial membrane potential and decreased reactive oxygen species levels under hypoxic conditions for 72 hours.ConclusionThese results will be used as basic data for understanding the mechanism of how trophoblast cells respond to oxidative stress and how selenium promotes the upregulation of related genes and improves the survival rate and invasive ability of trophoblasts through regulating mitochondrial activity. These results suggest that selenium may be used in reproductive medicine for purposes including infertility treatment.

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“…Iriyama et al [11] revealed that a local increase of adenosine in the placenta is sufficient to trigger key features of preeclampsia using mouse models, and adenosine was identified as one of pathogenic factors for preeclampsia. A2B receptor activation has been shown to blunt trophoblast migration, possibly as a result of reduced activation of the ERK1/2 and SAPK/JNK signaling pathway and lower proMMP-2 and VEGF levels, which are crucial for trophoblast function [9]. These observations suggest the possible involvement of adenosine receptors in placental developmental processes.…”

Section: Introductionmentioning

confidence: 94%

“…Adenosine is a potent immunomodulatory biomolecule that is produced by the ectoenzymes nucleoside triphosphate dephosphorylase (CD39) and ecto-5′-nucleotidase (CD73), which are highly expressed by several cell types, including leukocytes, during stress, injury, and infection [ 8 ]. Extracellular adenosine levels increase in response to hypoxia, ischemia and inflammation, preventing tissue damage during instances of cellular stress or injury [ 9 ]. The effects of adenosine are mediated via 4 adenosine receptor (AR) subtypes: A 1 AR, A 2A AR, A 2B AR, A 3 AR [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Adenosine A3 Receptor Mediates ERK1/2- and JNK-Dependent TNF-α Production in Toxoplasma gondii-Infected HTR8/SVneo Human Extravillous Trophoblast Cells

Sun

et al. 2020

Korean J Parasitol

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Toxoplasma gondii is an intracellular parasite that causes severe disease when the infection occurs during pregnancy. Adenosine is a purine nucleoside involved in numerous physiological processes; however, the role of adenosine receptors in T. gondii-induced trophoblast cell function has not been investigated until now. The goal of the present study was to evaluate the intracellular signaling pathways regulated by adenosine receptors using a HTR-8/SVneo trophoblast cell model of T. gondii infection. HTR8/SVneo human extravillous trophoblast cells were infected with or without T. gondii and then evaluated for cell morphology, intracellular proliferation of the parasite, adenosine receptor expression, TNF-α production and mitogen-activated protein (MAP) kinase signaling pathways triggered by adenosine A3 receptor (A3AR). HTR8/SVneo cells infected with T. gondii exhibited an altered cytoskeletal changes, an increased infection rate and reduced viability in an infection time-dependent manner. T. gondii significantly promoted increased TNF-α production, A3AR protein levels and p38, ERK1/2 and JNK phosphorylation compared to those observed in uninfected control cells. Moreover, the inhibition of A3AR by A3AR siRNA transfection apparently suppressed the T. gondii infection-mediated upregulation of TNF-α, A3AR production and MAPK activation. In addition, T. gondii-promoted TNF-α secretion was dramatically attenuated by pretreatment with PD098059 or SP600125. These results indicate that A3AR-mediated activation of ERK1/2 and JNK positively regulates TNF-α secretion in T. gondii-infected HTR8/SVneo cells.

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Activation of adenosine A2B receptor impairs properties of trophoblast cells and involves mitogen-activated protein (MAP) kinase signaling

Cited by 15 publications

References 36 publications

Pregnancy exposure to atmospheric pollution and meteorological conditions and placental DNA methylation

Pregnancy exposure to atmospheric pollution and meteorological conditions and placental DNA methylation

Effects of selenium on the survival and invasion of trophoblasts

Adenosine A3 Receptor Mediates ERK1/2- and JNK-Dependent TNF-α Production in Toxoplasma gondii-Infected HTR8/SVneo Human Extravillous Trophoblast Cells

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