Butyl paraben promotes apoptosis in human trophoblast cells through increased oxidative stress-induced endoplasmic reticulum stress

The genes involved in implantation and placentation are tightly regulated to ensure a healthy pregnancy. The endoplasmic reticulum aminopeptidase 2 (ERAP2) gene is associated with preeclampsia (PE). Our studies have determined that an isoform of ERAP2-arginine (N), expressed in trophoblast cells (TC), significantly activates immune cells, and ERAP2N-expressing TCs are preferentially killed by both cytotoxic T lymphocytes (CTLs) and Natural Killer cells (NKCs). To understand the cause of this phenomenon, we surveyed differentially expressed genes (DEGs) between ERAP2N expressing and non-expressing TCs. Our RNAseq data revealed 581 total DEGs between the two groups. 289 genes were up-regulated, and 292 genes were down-regulated. Interestingly, most of the down-regulated genes of significance were pro-survival genes that play a crucial role in cell survival (LDHA, EGLN1, HLA-C, ITGB5, WNT7A, FN1). However, the down-regulation of these genes in ERAP2N-expressing TCs translates into a propensity for cell death. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 64 DEGs were significantly enriched in nine pathways, including “Protein processing in endoplasmic reticulum” and “Antigen processing and presentation”, suggesting that the genes may be associated with peptide processes involved in immune recognition during the reproductive cycle.

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Galectin 14 protects human trophoblast cells from oxidative stress and promotes extravillous differentiation

Fertility and Sterility ◽

10.1016/j.fertnstert.2015.07.261 ◽

2015 ◽

Vol 104 (3) ◽

pp. e85

Author(s):

R. Fritz ◽

B. Kilburn ◽

H. Kohan-Ghadr ◽

S. Drewlo ◽

D. Armant

Keyword(s):

Oxidative Stress ◽

Trophoblast Cells ◽

Human Trophoblast ◽

Human Trophoblast Cells

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sFlt-1 commutes unfolded protein response into endoplasmic reticulum stress in trophoblast cells in preeclamptic pregnancies

10.1101/297374 ◽

2018 ◽

Author(s):

Sankat Mochan ◽

Manoj Kumar Dhingra ◽

Sunil Kumar Gupta ◽

Shobhit saxena ◽

Pallavi Arora ◽

...

Keyword(s):

Oxidative Stress ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Er Stress ◽

Late Onset ◽

Trophoblast Cells ◽

Bewo Cells ◽

Placental Cells

AbstractPreeclampsia (PE) and its subtypes (early and late onset) are serious concerns all across the globe affecting about 8% of total pregnancies and accounts for approximately 60,000 deaths annually with a predominance in developing under-developed and countries. The two-stage model in the progression of this disease, deficient spiral artery remodelling and an imbalance between angiogenic (VEGF) and anti-antigenic factor(s) (sFlt-1) are well established facts pertaining to this disease. The presence of increased sFlt-1, high oxidative stress and Endoplasmic reticulum stress (ER stress) have been proposed in preeclamptic pregnancies. Recently, the role of endoplasmic reticulum stress in the onset of the variant forms of PE highlighted a new window to explore further. In our previous studies, we demonstrated that sFlt-1 can induce apoptosis and oxidative stress in trophoblast cells. However the role of sFlt-1, in inducing ER stress is not known so far. In the present study, we for the first time demonstrated significant ER stress in the placental cells (BeWo Cells) (in vitro) when exposed to sera from preeclamptic pregnancies having increased concentration of sFlt-1. The expression of ER stress markers (GRP78, eIF2α, XBP1, ATF6 and CHOP) at both transcript and protein levels were compared (between preeclamptic and normotensive non-proteinuric women) at three different time points (8h, 14h and 24hrs), analyzed and found to be significant (p<0.05).ConclusionOur results suggested that sFlt-1, released from placental cells in preeclampsia may be one of the various factors having potential to induce endoplasmic reticulum stress in BeWo cells.

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Abstract #403: The Glutathione Mimic Ebselen Inhibits Oxidative Stress but not Endoplasmic Reticulum Stress in Endothelial Cells.

Endocrine Practice ◽

10.1016/s1530-891x(20)42618-7 ◽

2015 ◽

Vol 21 ◽

pp. 85-86

Author(s):

William Kurban ◽

Salma Makhoul Ahwach ◽

Melanie Thomas ◽

Luisa Onsteed-Haas ◽

Michael Haas

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress

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Abstract #402: Beta Blockers Suppress Dextrose-Induced Endoplasmic Reticulum Stress, Oxidative Stress and Apoptosis in Human Coronary Artery Endothelial Cells.

Endocrine Practice ◽

10.1016/s1530-891x(20)42617-5 ◽

2015 ◽

Vol 21 ◽

pp. 85

Author(s):

Harshit Shah ◽

William Kurban ◽

Luisa Onstead-Haas ◽

Michael Haas ◽

Arshag Mooradian

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Endoplasmic Reticulum ◽

Coronary Artery ◽

Endoplasmic Reticulum Stress ◽

Beta Blockers ◽

Human Coronary Artery ◽

Stress Oxidative

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Testicular Injury Attenuated by Rapamycin Through Induction of Autophagy and Inhibition of Endoplasmic Reticulum Stress in Streptozotocin- Induced Diabetic Rats

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530319666190102112844 ◽

2019 ◽

Vol 19 (5) ◽

pp. 665-675 ◽

Cited By ~ 4

Author(s):

Wenjiao Shi ◽

Zhixin Guo ◽

Ruixia Yuan

Keyword(s):

Oxidative Stress ◽

Endoplasmic Reticulum ◽

Endoplasmic Reticulum Stress ◽

Protective Effect ◽

Er Stress ◽

B Cell Lymphoma ◽

Diabetic Rats ◽

Pathological Changes ◽

Rapamycin Treatment ◽

Related Proteins

Background and Objective: This study investigated whether rapamycin has a protective effect on the testis of diabetic rats by regulating autophagy, endoplasmic reticulum stress, and oxidative stress. Methods: Thirty male Sprague-Dawley rats were randomly divided into three groups: control, diabetic, and diabetic treated with rapamycin, which received gavage of rapamycin (2mg.kg-1.d-1) after induction of diabetes. Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ, 65mg.Kg-1). All rats were sacrificed at the termination after 8 weeks of rapamycin treatment. The testicular pathological changes were determined by hematoxylin and eosin staining. The protein or mRNA expression of autophagy-related proteins (Beclin1, microtubule-associated protein light chain 3 (LC3), p62), ER stress marked proteins (CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP), caspase-12), oxidative stress-related proteins (p22phox, nuclear factor erythroid2-related factor 2 (Nrf2)) and apoptosis-related proteins (Bax, B cell lymphoma-2 (Bcl-2)) were assayed by western blot or real-time fluorescence quantitative PCR. Results: There were significant pathological changes in the testes of diabetic rats. The expression of Beclin1, LC3, Nrf2, Bcl-2 were significantly decreased and p62, CHOP, caspase12, p22phox, and Bax were notably increased in the testis of diabetic rats (P <0.05). However, rapamycin treatment for 8 weeks significantly reversed the above changes in the testis of diabetic rats (P <0.05). Conclusion: Rapamycin appears to produce a protective effect on the testes of diabetic rats by inducing the expression of autophagy and inhibiting the expression of ER-stress, oxidative stress, and apoptosis.

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