scholarly journals MiR-133a-3p Relieves the Oxidative Stress Induced Trophoblast Cell Apoptosis Through the BACH1/Nrf2/HO-1 Signaling Pathway

2021 ◽  
pp. 67-78
Author(s):  
H GUO ◽  
Y WANG ◽  
W JIA ◽  
L LIU
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Trophoblast Cell ◽  
Trophoblast Cells ◽  
Antioxidant Genes ◽  
Binding Effect ◽  
Pregnancy Morbidity ◽  
Regulatory Effects ◽  
New Perspective ◽  
Induced Apoptosis

Preeclampsia (PE) is a major cause of the pregnancy morbidity and mortality over the world. Disorganized placentation caused by trophoblast cell abnormity is one of main risk factors to induce PE. MiR-133a-3p has been shown to contain regulatory effects on oxidative stress in the cardiomyocytes. But the effects of miR-133a-3p on oxidative stress-induced apoptosis in the trophoblast cells remain unknown. In this study, trophoblast HTR-8/SVneo cells were transfected with miR-133a-3p mimics and inhibitor. H2O2 (250 μM) treatment of cells was adopted to induce oxidative stress. A series of typical molecular and cellular experiments was subsequently performed in order to investigate this issue. It was found that miR-133a-3p overexpression attenuated the oxidative stress induced by H2O2 through reduced ROS and MDA levels and enhanced antioxidase activities in the trophoblast cells. Overexpressed miR-133a-3p was shown to relieve the oxidative stress-induced apoptosis of HTR-8/SVneo cells. At molecular levels, a direct binding effect of miR-133a-3p on BACH1 was verified. Moreover, miR-133a-3p overexpression also enhanced BACH1 downstream Nrf2/HO-1 signaling to activate antioxidant genes. It is collectively demonstrated that miR-133a-3p can relieve the oxidative stress-induced apoptosis in the trophoblast cells through the BACH1/Nrf2/HO-1 signaling pathway via targeting BACH1 directly. This regulatory mechanism of miR-133a-3p in the trophoblast cells under oxidative stress may give a new perspective for oxidative stress-induced trophoblast cell abnormality and be useful to study more pathological mechanisms of PE.

HSP20 Exerts a Protective Effect on Preeclampsia by Regulating Function of Trophoblast Cells Via Akt Pathways

2018 ◽  
Vol 26 (7) ◽  
pp. 961-971 ◽  
Author(s):  
Fanfan Li ◽  
Yin Xie ◽  
Yuanyuan Wu ◽  
Mengzhou He ◽  
Meitao Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Extravillous Trophoblast ◽  
Akt Signaling Pathway ◽  
Trophoblast Cells ◽  
Heat Shock Protein 20 ◽  
Apoptosis Index ◽  
Proliferation And Apoptosis ◽  
Associated Proteins

Preeclampsia (PE) remains the leading cause of maternal and fetal morbidity and mortality. Excessive apoptosis of the placenta and poor remodeling of spiral arteries caused by insufficient invasion of trophoblast cells into uterus have been implicated in the pathogenesis of PE. Accumulating evidence showed that heat shock protein 20 (HSP20) is closely associated with the proliferation, apoptosis, and metastasis of tumor cells. However, little is known about whether HSP20 plays a role in the development of PE. In this study, we detected the apoptosis index and the expressions of HSP20 and apoptosis-associated proteins in the placentas from PE and normal pregnancies. We found that HSP20 was reversely related to the apoptosis rate and the levels of proapoptotic proteins. Moreover, we identified that HSP20 could suppress the proliferation and apoptosis of trophoblast cells, turning them into a more invasive phenotype. Additionally, H2O2-induced oxidative stress was significantly alleviated, and several key proteins on the Akt signaling pathway were upregulated in HSP20-overexpressing trophoblast cells. These findings strongly suggested that HSP20 might play a role in the remodeling of spiral arteries through affecting the invasiveness of extravillous trophoblast cells via Akt signaling pathway, and the dysregulation of it might contribute to the pathophysiology of PE.

Human 8-Oxoguanine DNA Glycosylase Suppresses the Oxidative Stress–Induced Apoptosis through a p53-Mediated Signaling Pathway in Human Fibroblasts

2007 ◽  
Vol 5 (10) ◽  
pp. 1083-1098 ◽  
Author(s):  
Cha-Kyung Youn ◽  
Peter I. Song ◽  
Mi-Hwa Kim ◽  
Jin Sook Kim ◽  
Jin-Won Hyun ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Human Fibroblasts ◽  
Dna Glycosylase ◽  
Induced Apoptosis

scholarly journals Emodin Alleviates Hydrogen Peroxide-Induced Inflammation and Oxidative Stress via Mitochondrial Dysfunction by Inhibiting the PI3K/mTOR/GSK3β Pathway in Neuroblastoma SH-SY5Y Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Rui Li ◽  
Wenzhou Liu ◽  
Li Ou ◽  
Feng Gao ◽  
Min Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Cell Damage ◽  
Neuroblastoma Cells ◽  
Inflammatory Factors ◽  
Protective Mechanism ◽  
Human Neuroblastoma ◽  
Induced Apoptosis

Emodin is an active monomer extracted from rhubarb root, which has many biological functions, including anti-inflammation, antioxidation, anticancer, and neuroprotection. However, the protective effect of emodin on nerve injury needs to be further elucidated. The purpose of this study is to investigate the effect of emodin on the neuroprotection and the special molecular mechanism. Here, the protective activity of emodin inhibiting H2O2-induced apoptosis and neuroinflammation as well as its molecular mechanisms was examined using human neuroblastoma cells (SH-SY5Y cells). The results showed that emodin significantly enhanced cell viability, reduced cell apoptosis and LDH release. Simultaneously, emodin downregulated H2O2-induced inflammatory factors, including IL-6, NO, and TNF-α, and alleviated H2O2-induced oxidative stress and mitochondrial dysfunction in SH-SY5Y cells. In addition, emodin inhibited the activation of the PI3K/mTOR/GSK3β signaling pathway. What is more, the PI3K/mTOR/GSK3β pathway participated in the protective mechanism of emodin on H2O2-induced cell damage. Collectively, it suggests that emodin alleviates H2O2-induced apoptosis and neuroinflammation potentially by regulating the PI3K/mTOR/GSK3β signaling pathway.

microRNA-29b contributes to pre-eclampsia through its effects on apoptosis, invasion and angiogenesis of trophoblast cells

2012 ◽  
Vol 124 (1) ◽  
pp. 27-40 ◽  
Author(s):  
Pengfei Li ◽  
Wei Guo ◽  
Leilei Du ◽  
Junli Zhao ◽  
Yaping Wang ◽  
...  
Keyword(s):  
Target Genes ◽  
Inverse Correlation ◽  
Myeloid Cell ◽  
Trophoblast Cell ◽  
Trophoblast Invasion ◽  
Cell Leukaemia ◽  
Trophoblast Cells ◽  
Computer Based ◽  
Induced Apoptosis ◽  
Endothelial Growth Factor

PE (pre-eclampsia), a pregnancy-specific disorder, is characterized by increased trophoblast cell death and deficient trophoblast invasion and reduced trophoblast-mediated remodelling of spiral arteries. The present study was performed to determine the function of miR-29b (microRNA-29b) in trophoblast cells and its underlying role in the pathogenesis of PE. The prediction of miR-29b target genes was performed using computer-based programs, including Targetscan, Pictar and miRBase. The function of these target genes was analysed further by gene ontology (GO). The effects of miR-29b on apoptosis, and invasion and angiogenesis of trophoblast cell lines (HTR-8/SVneo, BeWo and JAR) were examined by flow cytometry and Matrigel assay respectively. We found that miR-29b induced apoptosis and inhibited invasion and angiogenesis of trophoblast cells. Further studies confirmed that miR-29b regulated the expression of MCL1 (myeloid cell leukaemia sequence 1), MMP2 (encoding matrix metallproteinase 2), VEGFA (vascular endothelial growth factor A) and ITGB1 (integrin β1) genes by directly binding to their 3′-UTRs (untranslated regions). Moreover, we identified that there was an inverse correlation between miR-29b and its target genes in subjects with PE. Taken together, these findings support a novel role for miR-29b in invasion, apoptosis and angiogenesis of trophoblast cells, and miR-29b may become a new potential therapeutic target for PE.

ARNT Mediates Chemotherapy Resistance by Modulating the Response to Oxidative Stress in AML Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2737-2737
Author(s):  
Richard A. Wells ◽  
Chunhong Gu ◽  
Joelle dela Paz
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Cell Lines ◽  
Akt Signaling ◽  
Mrna Levels ◽  
Antioxidant Genes ◽  
Protein Levels ◽  
Exogenous Expression ◽  
Induction Of Apoptosis ◽  
Induced Apoptosis

Abstract Abstract 2737 Poster Board II-713 Background Although patients with acute myelogenous leukaemia (AML) typically respond well to initial therapy, with over 75% of patients achieving complete remission, in the great majority the disease ultimately relapses. This is thought to be due to the inherent resistance of leukaemia stem cells to the effects of chemotherapy. While some mechanisms of chemoresistance, e.g. TP53 mutation and upregulation of P-glycoprotein expression, have been well characterized, this phenomenon remains incompletely understood and is a significant barrier to improving patient outcomes. Methods and results The thiazolidindione drug troglitazone (TG) induces apoptosis in AML cells via generation of intracellular reactive oxygen species (ROS), but the degree of sensitivity to TG is highly heterogeneous among AML cell lines. We studied expression of the transcription factor ARNT (aryl hydrocarbon nuclear translocator) in TG-sensitive and TG-resistant AML cell lines following TG treatment. In HL-60 cells, which are highly sensitive to induction of apoptosis by TG, ARNT mRNA levels remained constant following TG treatment and ARNT protein levels markedly decreased, while in U937 cells, which are TG resistant, ARNT mRNA levels increased and ARNT protein levels remained constant. We then tested the effect of exogenous expression of ARNT on the sensitivity of HL-60 cells to TG-induced apoptosis. HL-60 cells transduced with a retrovirus expressing ARNT became TG-resistant. Exogenous expression of ARNT also conferred resistance to induction of apoptosis by hydrogen peroxide, daunorubicin and etoposide. The cellular response to oxidative stress is governed by intracellular signaling pathways and through a transcriptional response through which expression of antioxidant genes is coordinated. HL-60 cells expressing ARNT had striking constitutive activation of AKT signaling, and treatment of these cells with a specific inhibitor of AKT signaling reversed their resistance to TG-induced apoptosis. The activation of AKT signaling by ARNT appears to be mediated by downregulation of expression of PP2A and alpha4, two key negative regulators of AKT phosphorylation. In addition, ARNT-transduced HL-60 cells showed increased expression of Nrf2, a key transcriptional regulator of the antioxidant response, and its target genes SOD2 and CAT. Conclusions The response to oxidative stress is heterogeneous in AML cells lines, and varies with expression of ARNT. ARNT activates expression of Nrf2, which stimulates expression of antioxidant genes resulting in an augmented adaptive response to ROS. Unexpectedly, ARNT also activates AKT signaling by repressing expression of the regulatory phosphatases PP2A and alpha4. These activities of ARNT result in increased resistance to the induction of apoptosis by TG, hydrogen peroxide, and chemotherapy. ARNT may play an important role in chemoresistance in and may be useful as a predictive or prognostic biomarker. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Antcin C fromAntrodia cinnamomeaProtects Liver Cells Against Free Radical-Induced Oxidative Stress and ApoptosisIn VitroandIn Vivothrough Nrf2-Dependent Mechanism

2013 ◽  
Vol 2013 ◽  
pp. 1-17 ◽  
Author(s):  
M. Gokila Vani ◽  
K. J. Senthil Kumar ◽  
Jiunn-Wang Liao ◽  
Shih-Chang Chien ◽  
Jeng-Leun Mau ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Transcriptional Activation ◽  
Liver Cells ◽  
Ros Generation ◽  
Antioxidant Genes ◽  
Pi3k Activation ◽  
Mice Liver ◽  
Induced Apoptosis

In this study, we investigated the cytoprotective effects of antcin C, a steroid-like compound isolated from Antrodia cinnamaomea against AAPH-induced oxidative stress and apoptosis in human hepatic HepG2 cells. Pretreatment with antcin C significantly protects hepatic cells from AAPH-induced cell death through the inhibition of ROS generation. Furthermore, AAPH-induced lipid peroxidation, ALT/AST secretion and GSH depletion was significantly inhibited by antcin C. The antioxidant potential of antcin C was correlated with induction of antioxidant genes including, HO-1, NQO-1,γ-GCLC, and SODviatranscriptional activation of Nrf2. The Nrf2 activation by antcin C is mediated by JNK1/2 and PI3K activation, whereas pharmacologic inhibition of JNK1/2 and PI3K abolished antcin C-induced Nrf2 activity. In addition, AAPH-induced apoptosis was significantly inhibited by antcin C through the down-regulation of pro-apoptotic factors including, Bax, cytochrome c, capase 9, -4, -12, -3, and PARP.In vivostudies also show that antcin C significantly protected mice liver from AAPH-induced hepatic injury as evidenced by reduction in hepatic enzymes in circulation. Further, immunocytochemistry analyses showed that antcin C significantly increased HO-1 and Nrf2 expression in mice liver tissues. These results strongly suggest that antcin C could protect liver cells from oxidative stress and cell deathviaNrf2/ARE activation.

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