scholarly journals NRF2-mediated signaling is a master regulator of transcription factors in bovine granulosa cells under oxidative stress condition

2021 ◽  
Author(s):  
Mohamed Omar Taqi ◽  
Mohammed Saeed-Zidane ◽  
Samuel Gebremedhn ◽  
Dessie Salilew-Wondim ◽  
Ernst Tholen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Endoplasmic Reticulum ◽  
Transcription Factors ◽  
Endoplasmic Reticulum Stress ◽  
Granulosa Cells ◽  
Mitochondrial Activity ◽  
Small Interference Rna ◽  
Nrf2 Signaling Pathway

AbstractTranscription factors (TFs) are known to be involved in regulating the expression of several classes of genes during folliculogenesis. However, the regulatory role of TFs during oxidative stress (OS) is not fully understood. The current study was aimed to investigate the regulation of the TFs in bovine granulosa cells (bGCs) during exposure to OS induced by H2O2 in vitro. For this, bGCs derived from ovarian follicles were cultured in vitro till their confluency and then treated with H2O2 for 40 min. Twenty-four hours later, cells were subjected to various phenotypic and gene expression analyses for genes related to TFs, endoplasmic reticulum stress, apoptosis, cell proliferation, and differentiation markers. The bGCs exhibited higher reactive oxygen species accumulation, DNA fragmentation, and endoplasmic reticulum stress accompanied by reduction of mitochondrial activity after exposure to OS. In addition, higher lipid accumulation and lower cell proliferation were noticed in H2O2-challenged cells. The mRNA level of TFs including NRF2, E2F1, KLF6, KLF9, FOS, SREBF1, SREBF2, and NOTCH1 was increased in H2O2-treated cells compared with non-treated controls. However, the expression level of KLF4 and its downstream gene, CCNB1, were downregulated in the H2O2-challenged group. Moreover, targeted inhibition of NRF2 using small interference RNA resulted in reduced expression of KLF9, FOS, SREBF2, and NOTCH1 genes, while the expression of KLF4 was upregulated. Taken together, bovine granulosa cells exposed to OS exhibited differential expression of various transcription factors, which are mediated by the NRF2 signaling pathway.

scholarly journals Methane Alleviates Acetaminophen-Induced Liver Injury by Inhibiting Inflammation, Oxidative Stress, Endoplasmic Reticulum Stress, and Apoptosis through the Nrf2/HO-1/NQO1 Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Yang Feng ◽  
Ruixia Cui ◽  
Zeyu Li ◽  
Xia Zhang ◽  
Yifan Jia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Liver Injury ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathway ◽  
Hepatic Injury ◽  
Protective Effects ◽  
Serum Aminotransferase ◽  
Anti Inflammatory

Acetaminophen- (APAP-) induced hepatic injury is an important clinical challenge. Oxidative stress, inflammation, apoptosis, and endoplasmic reticulum stress (ERS) contribute to the pathogenesis. Methane has potential anti-inflammatory, antioxidant, and antiapoptotic properties. This project was aimed at studying the protective effects and relative mechanisms of methane in APAP-induced liver injury. In the in vivo experiment, C57BL/6 mice were treated with APAP (400 mg/kg) to induce hepatic injury followed by methane-rich saline (MRS) 10 ml/kg i.p. after 12 and 24 h. We observed that MRS alleviated the histopathological lesions in the liver, decreased serum aminotransferase levels, reduced the levels of inflammatory cytokines, suppressed the nuclear factor-κB expression. Further, we found that MRS relieved oxidative stress by regulating the Nrf2/HO-1/NQO1 signaling pathway and their downstream products after APAP challenge. MRS also regulated proteins associated with ERS-induced apoptosis. In the in vitro experiment, the L-02 cell line was treated with APAP (10 mM) to induce hepatic injury. We found that a methane-rich medium decreased the levels of reactive oxygen species (DHE fluorescent staining), inhibited apoptosis (cell flow test), and regulated the Nrf2/HO-1/NQO1 signaling pathway. Our data indicated that MRS prevented APAP-induced hepatic injury via anti-inflammatory, antioxidant, anti-ERS, and antiapoptotic properties involving the Nrf2/HO-1/NQO1 signaling pathway.

scholarly journals Berberine Improved Aldo-Induced Podocyte Injury via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress Pathways both In Vivo and In Vitro

2016 ◽  
Vol 39 (1) ◽  
pp. 217-228 ◽  
Author(s):  
Bin Wang ◽  
Xianlin Xu ◽  
Xiaozhou He ◽  
Zhigang Wang ◽  
Min Yang
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Annexin V ◽  
Isoquinoline Alkaloid ◽  
Sprague Dawley ◽  
Podocyte Injury ◽  
Transmission Electron

Background/Aims: Berberine, a naturally occurring isoquinoline alkaloid, acts against oxidative stress (OS) and endoplasmic reticulum stress (ERS), both of which are responsible for Aldosterone (Aldo) -induced podocyte injury. However, the direct effects of berberine on Aldo-induced OS, ERS, and podocyte injury are not well defined. Methods: Uninephrectomized Sprague-Dawley rats were given 1% NaCl (salt) in their water and an Aldo infusion (0.75 µg/h) for 28 days to induce podocyte injury in the Aldo group. In the Aldo/berberine group, in addition to Aldo infusion, rats were administered 150 mg/kg berberine per day by gastric gavage for 4 weeks. Podocytes were incubated in media containing either buffer or Aldo in the presence or absence of berberine for variable time periods. The kidney tissues and podocytes were then investigated using morphological analysis, immunohistochemistry, transmission electron microscopy, western blot, DHE staining, DCFDA fluorescence, and Annexin V staining. Results: Here, we have reported that berberine attenuated Aldo-induced OS, ERS, and podocyte injury both in vivo and in vitro. Additionally, berberine treatment improved the extensive fusion of foot processes in electron micrographs resulting from Aldo/salt infusion in rats. Conclusion: Berberine may be examined as an effective agent against Aldo-induced podocyte injury.

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

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.

scholarly journals Curcumin Improves Epithelial Barrier Integrity of Caco-2 Monolayers by Inhibiting Endoplasmic Reticulum Stress and Subsequent Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xinxin Zhou ◽  
Mengting Ren ◽  
Jinpu Yang ◽  
Hanghai Pan ◽  
Mosang Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Cell Apoptosis ◽  
Epithelial Barrier ◽  
Intestinal Epithelial ◽  
Barrier Integrity ◽  
Protein Levels ◽  
Coculture Model

Curcumin is a natural polyphenol and is supposed to possess antioxidant, anti-inflammatory, anticancer, and antiapoptotic properties. Although some studies have reported the therapeutic effects of curcumin on ulcerative colitis (UC), the specific mechanism remains unclear. An in vitro coculture model of Caco-2 and differentiated THP-1 cells was established. After administration of curcumin (10 μM), Western blot analysis was performed to evaluate the protein levels of tight junction (TJ) proteins zonula occludens- (ZO-) 1 and claudin-1. Annexin V-APC/7-AAD assays and flow cytometry were conducted to assess Caco-2 cell apoptosis. The expression levels of oxidative stress and endoplasmic reticulum stress- (ERS-) related molecules were determined by Western blot analysis. Curcumin administration significantly upregulated ZO-1 and claudin-1 protein levels and reduced Caco-2 cell apoptosis. The protein levels of oxidative stress markers inducible nitric oxide synthase (iNOS) and γH2AX and ERS-induced apoptosis-related molecules C/EBP homologous protein (CHOP) and cleaved caspase-12 were significantly downregulated upon curcumin treatment. Furthermore, curcumin administration greatly blocked the protein kinase-like endoplasmic reticulum kinase- (PERK-) eukaryotic translation initiation factor 2α- (eIF2α-) activating transcription factor 4- (ATF4-) CHOP signaling pathway. Curcumin enhanced intestinal epithelial barrier integrity in the in vitro coculture model by upregulating TJ protein expressions and reducing intestinal epithelial cell apoptosis. The potential mechanisms may be suppression of ERS and subsequent apoptosis.

Mdivi-1 Protects Epileptic Hippocampal Neurons from Apoptosis via Inhibiting Oxidative Stress and Endoplasmic Reticulum Stress in Vitro

2016 ◽  
Vol 41 (6) ◽  
pp. 1335-1342 ◽  
Author(s):  
Nanchang Xie ◽  
Cui Wang ◽  
Chuanjie Wu ◽  
Xuan Cheng ◽  
Yanlun Gao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Hippocampal Neurons

scholarly journals Effects of Grape Seed Extract and Proanthocyanidin B2 on In Vitro Proliferation, Viability, Steroidogenesis, Oxidative Stress, and Cell Signaling in Human Granulosa Cells

2019 ◽  
Vol 20 (17) ◽  
pp. 4215 ◽  
Author(s):  
Alix Barbe ◽  
Christelle Ramé ◽  
Namya Mellouk ◽  
Anthony Estienne ◽  
Alice Bongrani ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Granulosa Cells ◽  
Grape Seed Extract ◽  
Grape Seed ◽  
Seed Extract ◽  
Cell Content ◽  
Human Granulosa Cells

Reactive oxygen species (ROS) which lead to oxidative stress affect ovarian function. Grape seed extract (GSE) could be proposed as an effective antioxidant, particularly due to its proanthocyanidin content. In this study, we investigated a dose effect (0, 0.01, 0.1, 1, 10, 50, and 100 μg/mL) of GSE and proanthocyanidin B2 (GSPB2) on the ROS content, cell proliferation, cell viability, and steroidogenesis in both primary luteinized granulosa cells (hGC) and the tumor granulosa cell line (KGN). The levels of ROS were measured using ROS-Glo assay. Cell proliferation and viability were evaluated by [3H]-thymidine incorporation and Cell Counting Kit-8 (CCK8) assay, respectively. Steroid secretion was evaluated by radioimmunoassay. We also analyzed the cell cycle component protein level and signaling pathways by immunoblot and the NOX4 mRNA expression by RTqPCR. From 0.1 to 1 μg/mL, GSE and GSBP2 reduced the ROS cell content and the NOX4 mRNA levels, whereas, GSE and GSBP2 increased the ROS cell content from 50 to 100 μM in both hGC and KGN. GSE and GSPB2 treatments at 50 and 100 μg/mL induced a delay in G1 to S phase cell cycle progression as determined by fluorescence-activated cell sorting. Consequently, they reduced cell growth, cyclin D2 amount, and Akt phosphorylation, and they increased protein levels of p21 and p27 cyclin-dependent kinase inhibitors. These data were also associated with an increase in cell death that could be due to a reduction in Bcl-2-associated death promoter (BAD) phosphorylation and an increase in the cleaved-caspase-3 level. All these negative effects were not observed at lower concentrations of GSE and GSPB2 (0.01 to 10 μg/mL). Interestingly, we found that GSE and GSPB2 treatments (0.1 to 100 μg/mL) improved progesterone and estradiol secretion and this was associated with a higher level of the cholesterol carriers, StAR (steroidogenic acute regulatory protein), CREB (Cyclic adenosine monophosphate Response Element-binding protein), and MAPK ERK1/2 (Mitogen-Activated Protein Kinases Extracellular signal-Regulated Kinases 1/2) phosphorylation in both hGC and KGN cells. Taken together, GSE and GSPB2 (0.1–10 μg/mL) in vitro treatments decrease oxidative stress and increase steroidogenesis without affecting cell proliferation and viability in human granulosa cells.

scholarly journals Acetaldehyde Induces Neurotoxicity In Vitro via Oxidative Stress- and Ca2+ Imbalance-Mediated Endoplasmic Reticulum Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Jiahui Cui ◽  
Yang Liu ◽  
Xing Chang ◽  
Wenfeng Gou ◽  
Xuejiao Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Early Stage ◽  
Neuronal Cells ◽  
Toxic Metabolite ◽  
Related Protein ◽  
Ht22 Cells ◽  
Induced Apoptosis

Excessive drinking can damage brain tissue and cause cognitive dysfunction. Studies have found that the early stage of neurodegenerative disease is closely related to heavy drinking. Acetaldehyde (ADE) is the main toxic metabolite of alcohol. However, the exact mechanisms of ADE-induced neurotoxicity are not fully clear. In this article, we studied the cytotoxic effect of ADE in HT22 cells and primary cultured cortical neuronal cells. We found that ADE exhibited cytotoxicities against HT22 cells and primary cultured cortical neuronal cells in dose-dependent manners. Furthermore, ADE induced apoptosis of HT22 cells by upregulating the expression of caspase family proapoptotic proteins. Moreover, ADE treatment could significantly increase the intracellular Ca2+ and reactive oxygen species (ROS) levels and activate endoplasmic reticulum stress (ERS) in HT22 cells. ADE upregulated ERS-related CHOP expression dose-dependently in primary cultured cortical neuronal cells. In addition, inhibition of ROS with antioxidant N-acetyl-L-cysteine (NAC) reduced the accumulation of ROS and reversed ADE-induced increase of ERS-related protein and apoptosis-related protein levels. Mitigation of ERS with ERS inhibitor 4-PBA obviously suppressed ADE-induced apoptosis and the expression of ERS-related proteins. Therefore, ADE induces neurotoxicity of HT22 cells via oxidative stress- and Ca2+ imbalance-mediated ERS.

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