Punicalagin promotes autophagy to protect primary human syncytiotrophoblasts from apoptosis

Wang, Ying; Chen, Baosheng; Longtine, Mark S.; Nelson, D. Michael

doi:10.1530/rep-15-0287

Cited by 31 publications

(23 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Toward the end of pregnancy, preeclampsia is associated with high levels of placental autophagy, including the syncytiotrophoblast . The current results corroborate previous studies showing the activation of autophagy in in vitro models of human villous trophoblasts exposed to lower oxygen levels . As expected, the activation of the autophagic pathway was not modulated by melatonin in normoxia .…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

Melatonin modulates autophagy and inflammation protecting human placental trophoblast from hypoxia/reoxygenation

Sagrillo-Fagundes

Salustiano

Ruano

et al. 2018

Journal of Pineal Research

View full text Add to dashboard Cite

Melatonin has been proposed as a possible treatment for the deleterious effects of hypoxia/reoxygenation (H/R), such as autophagy, inflammation, and apoptosis. Pathological pregnancies, such as preeclampsia, are associated with placental H/R, and decreased placental melatonin synthesis as well as lower melatonin levels in the placenta and maternal plasma. However, the effects of exogenous melatonin on inflammation and autophagy induced by pregnancy complications associated with H/R await investigation. This study aimed to determine as to whether melatonin protects human primary villous trophoblasts against H/R-induced autophagy, inflammation, and apoptosis. Human primary villous cytotrophoblasts were isolated and immunopurified from normal term placentas. These cells were then exposed or not to 1 mmol/L melatonin for 72 hour in normoxia (8% O ), thereby inducing differentiation into syncytiotrophoblast that was then exposed to H/R (0.5% O , for 4 hour) or normoxia. H/R decreased endogenous melatonin synthesis (by 68%) and interleukin (IL)-10 levels (by 72%), coupled to increased tumor necrosis factor (TNF) (by 114%), IL-6 (by 55%), and NFκB (by 399%), compared to normoxia. Melatonin treatment reversed the H/R effect, restoring IL-10, TNF, and IL-6 levels to those of the normoxia condition. Melatonin, as well as NFκB inhibition, enhanced autophagy activation, consequently increasing syncytiotrophoblast survival in H/R conditions. This study suggests that H/R, which is present in pregnancy complications, inhibits endogenous melatonin production, thereby contributing to reduced syncytiotrophoblast viability. Results indicate that exogenous melatonin treatment may afford protection against H/R-induced damage, thereby enhancing placental cell survival, and contributing to improved fetal outcomes.

show abstract

Section: Discussionsupporting

confidence: 91%

“…Previous studies have shown that hypoxic conditions led to activation of autophagy in human primary villous cytotrophoblasts . Beclin‐1 is a major activator of macroautophagy, referred herein simply as autophagy .…”

Section: Resultsmentioning

confidence: 99%

Melatonin modulates autophagy and inflammation protecting human placental trophoblast from hypoxia/reoxygenation

Sagrillo-Fagundes

Salustiano

Ruano

et al. 2018

Journal of Pineal Research

View full text Add to dashboard Cite

show abstract

“…46 The downregulation of Prdx2 might promote apoptosis of cultured syncytiotrophoblasts or the reduced Prdx2 might influence the signal pathways that is involved in syncytialization. 14, 47 The exact reason is lack of evidences and need further exploration.…”

Section: Discussionmentioning

confidence: 99%

Role of peroxiredoxin2 downregulation in recurrent miscarriage through regulation of trophoblast proliferation and apoptosis

Tian

Zeng

et al. 2017

Cell Death Dis

View full text Add to dashboard Cite

Peroxiredoxin (Prdx) 2 is an antioxidant protein that utilizes its redox-sensitive cysteine groups to reduce hydrogen peroxide molecules and protect cells against oxidative damage from reactive oxygen species (ROS). However, its function in trophoblasts at the maternal–fetal interface has not been clarified yet. In this study, significantly lower Prdx2 expression was found in the first-trimester villous cytotrophoblasts of patients with recurrent miscarriage (RM) than in cytotrophoblasts from healthy controls. Further, Prdx2 knockdown inhibited proliferation and increased apoptosis of trophoblast cells. The reason for this may be an increase in the level of cellular ROS after knockdown of Prdx2, which may subsequently lead to an increase in the expression of phosphorylated p53 (p-p53) and p38-MAPK/p21. Prdx2 knockdown also impaired the fusion of BeWo cells induced by forskolin. Bioinformatics analysis identified a c-Myc-binding site in the Prdx2 promoter region, and chromatin immunoprecipitation verified that c-Myc directly bound to a site in this locus. Suppression and overexpression of c-Myc resulted in reduction and increase of Prdx2 expression respectively. Furthermore, we demonstrated that c-Myc was downregulated in the first-trimester cytotrophoblasts of patients with RM, and its downregulation is also related with inhibited cell proliferation, increased apoptosis, as well as upregulated p21 expression and p-p53/p53 ratio. Our findings indicate that Prdx2 might have an important role in the regulation of trophoblast proliferation and apoptosis during early pregnancy, and that its expression is mediated by c-Myc. Thus, these two proteins may be involved in the pathogenesis of RM and may represent potential therapeutic targets.

show abstract

“…ELISA of cell extracts for active, DNA-binding NF-κB (1007889, Caymen Chemical), and of culture supernatants for secreted CD14 (DY382, R&D Systems), secreted IL-6 (DY206, R&D Systems), secreted IL-8 (DY208, R&D Systems) and secreted TNF-α (DY201, R&D Systems) were performed according to the manufacturer's instructions. hCG ELISA were performed as described previously (Chen et al 2016).…”

Section: Elisamentioning

confidence: 99%

Calcitriol regulates immune genes CD14 and CD180 to modulate LPS responses in human trophoblasts

Longtine¹,

Cvitic²,

Colvin³

et al. 2017

Reproduction

Self Cite

View full text Add to dashboard Cite

We assessed the response of primary cultures of placental villous mononucleated trophoblasts and multinucleated syncytiotrophoblast to calcitriol, the most biologically active form of vitamin D. Whole-genome microarray data showed that calcitriol modulates the expression of many genes in trophoblasts within 6 hours of exposure and RT-qPCR revealed similar responses in cytotrophoblasts, syncytiotrophoblasts and villous explants. Both cytotrophoblasts and syncytiotrophoblasts expressed genes for the vitamin D receptor, for LRP2 and CUBN that mediate internalization of calcidiol, for that encodes the enzyme that converts calcidiol into active calcitriol, and for that encodes the enzyme that modifies calcitriol and calcidiol to inactive calcitetrol. Notably, we found an inverse effect of calcitriol on expression of CD14 and CD180/RP105, proteins that differentially regulate toll-like receptor 4-mediated immune responses. Supported by gene ontology analysis, we tested the hypothesis that CD14 and CD180 modulate the inflammatory response of syncytiotrophoblast to bacterial lipopolysaccharide (LPS). These cells showed a robust response to a wide range of LPS concentrations, with induction of active NF-κB and increased secretion of IL-6 and IL-8. SiRNA-mediated knockdown of reduced the secretion of IL-6 and IL-8 in response to LPS. Collectively, our data showed that calcitriol has a rapid and widespread effect on villous trophoblast gene expression in general, and a specific effect on the innate immune response by syncytiotrophoblast.

show abstract

Punicalagin promotes autophagy to protect primary human syncytiotrophoblasts from apoptosis

Cited by 31 publications

References 36 publications

Melatonin modulates autophagy and inflammation protecting human placental trophoblast from hypoxia/reoxygenation

Melatonin modulates autophagy and inflammation protecting human placental trophoblast from hypoxia/reoxygenation

Role of peroxiredoxin2 downregulation in recurrent miscarriage through regulation of trophoblast proliferation and apoptosis

Calcitriol regulates immune genes CD14 and CD180 to modulate LPS responses in human trophoblasts

Contact Info

Product

Resources

About