scholarly journals Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts

2012 ◽  
Vol 302 (9) ◽  
pp. E1142-E1152 ◽  
Author(s):  
Baosheng Chen ◽  
Methodius G. Tuuli ◽  
Mark S. Longtine ◽  
Joong Sik Shin ◽  
Russell Lawrence ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Human Placenta ◽  
Apple Juice ◽  
Kinase Inhibitor ◽  
Pomegranate Juice ◽  
Control Group ◽  
Induced Apoptosis

The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and suboptimal pregnancy outcomes. We tested the hypothesis that pomegranate juice, which is rich in polyphenolic antioxidants, limits placental trophoblast injury in vivo and in vitro. Pregnant women with singleton pregnancies were randomized at 35∼38 wk gestation to 8 oz/day of pomegranate juice or apple juice (placebo) until the time of delivery. Placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts. We conclude that pomegranate juice reduces placental oxidative stress in vivo and in vitro while limiting stimulus-induced death of human trophoblasts in culture. The polyphenol punicalagin mimics this protective effect. We speculate that antenatal intake of pomegranate may limit placental injury and thereby may confer protection to the exposed fetus.

scholarly journals iPLA2β Contributes to ER Stress-Induced Apoptosis during Myocardial Ischemia/Reperfusion Injury

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1446
Author(s):  
Tingting Jin ◽  
Jun Lin ◽  
Yingchao Gong ◽  
Xukun Bi ◽  
Shasha Hu ◽  
...  
Keyword(s):  
Cell Death ◽  
Heart Disease ◽  
Myocardial Ischemia ◽  
Ischemic Heart Disease ◽  
Er Stress ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion ◽  
Induced Apoptosis

Both calcium-independent phospholipase A2 beta (iPLA2β) and endoplasmic reticulum (ER) stress regulate important pathophysiological processes including inflammation, calcium homeostasis and apoptosis. However, their roles in ischemic heart disease are poorly understood. Here, we show that the expression of iPLA2β is increased during myocardial ischemia/reperfusion (I/R) injury, concomitant with the induction of ER stress and the upregulation of cell death. We further show that the levels of iPLA2β in serum collected from acute myocardial infarction (AMI) patients and in samples collected from both in vivo and in vitro I/R injury models are significantly elevated. Further, iPLA2β knockout mice and siRNA mediated iPLA2β knockdown are employed to evaluate the ER stress and cell apoptosis during I/R injury. Additionally, cell surface protein biotinylation and immunofluorescence assays are used to trace and locate iPLA2β. Our data demonstrate the increase of iPLA2β augments ER stress and enhances cardiomyocyte apoptosis during I/R injury in vitro and in vivo. Inhibition of iPLA2β ameliorates ER stress and decreases cell death. Mechanistically, iPLA2β promotes ER stress and apoptosis by translocating to ER upon myocardial I/R injury. Together, our study suggests iPLA2β contributes to ER stress-induced apoptosis during myocardial I/R injury, which may serve as a potential therapeutic target against ischemic heart disease.

scholarly journals A Higher Frequency Administration of the Nontoxic Cycloartane-Type Triterpene Argentatin A Improved Its Anti-Tumor Activity

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1780 ◽  
Author(s):  
Zaira Tavarez-Santamaría ◽  
Nadia J. Jacobo-Herrera ◽  
Leticia Rocha-Zavaleta ◽  
Alejandro Zentella-Dehesa ◽  
Beatriz del Carmen Couder-García ◽  
...  
Keyword(s):  
Waste Product ◽  
Industrial Process ◽  
Annexin V ◽  
Control Group ◽  
Healthy Control ◽  
Hct 116 ◽  
Hct 116 Cells ◽  
Induced Apoptosis

Parthenium argentatum (Gray), commonly known as guayule, has been used to obtain natural rubber since the beginning of the 20th century. Additionally, the so called “resin” is a waste product derived from the industrial process. The cycloartane-type triterpene Argentatin A (AA) is one of the main constituents of the industrial waste resin. In this study we evaluated the AA anticancer activity both in vitro and in vivo in the HCT116 colon cancer cells. The apoptosis promotion of AA was assessed by the annexin V/propidium iodide (PI) assay. The senescence was evaluated for SA-β-galactosidase, and PCNA was used as a marker of proliferation. Its antitumor activity was evaluated using a xenograft mouse model. The results indicated that AA-induced apoptosis in HCT-116 cells and was positively stained for SA-β-galactosidase. In the xenografted mice test, the administration of AA at the dose of 250 mg/kg three times a week for 21 days reduced tumor growth by 78.1%. A comparable tumor reduction was achieved with cisplatin at the dose of 2 mg/kg administered three times a week for 21 days. However, nude mice treated with AA did not lose weight, as they did remarkably when treated with cisplatin. Furthermore, the animals treated with AA showed similar blood profiles as the healthy control group. These data indicate the low toxicity of AA compared to that shown by cisplatin.

scholarly journals In Vitro and In Vivo Inhibitory Effect of Citrus Junos Tanaka Peel Extract against Oxidative Stress-Induced Apoptotic Death of Lung Cells

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1231
Author(s):  
Jin Woo Kim ◽  
Eun Hee Jo ◽  
Ji Eun Moon ◽  
Hanvit Cha ◽  
Moon Han Chang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protective Effect ◽  
Inhibitory Effect ◽  
Lung Cells ◽  
In Vivo Models ◽  
Citrus Junos ◽  
Induced Apoptosis ◽  
Peel Extract

Various stresses derived from both internal and external oxidative environments lead to the excessive production of reactive oxygen species (ROS) causing progressive intracellular oxidative damage and ultimately cell death. The objective of this study was to evaluate the protective effects of Citrus junos Tanaka peel extract (CE) against oxidative-stress induced the apoptosis of lung cells and the associated mechanisms of action using in vitro and in vivo models. The protective effect of CE was evaluated in vitro in NCI-H460 human lung cells exposed to pro-oxidant H2O2. The preventive effect of CE (200 mg/kg/day, 10 days) against pulmonary injuries following acrolein inhalation (10 ppm for 12 h) was investigated using an in vivo mouse model. Herein, we demonstrated the inhibitory effect of CE against the oxidative stress-induced apoptosis of lung cells under a highly oxidative environment. The function of CE is linked with its ability to suppress ROS-dependent, p53-mediated apoptotic signaling. Furthermore, we evaluated the protective role of CE against apoptotic pulmonary injuries associated with the inhalation of acrolein, a ubiquitous and highly oxidizing environmental respiratory pollutant, through the attenuation of oxidative stress. The results indicated that CE exhibits a protective effect against the oxidative stress-induced apoptosis of lung cells in both in vitro and in vivo models.

scholarly journals Adipose-Derived Mesenchymal Stem Cells Migrate and Rescue RPE in the Setting of Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Aya Barzelay ◽  
Shira Weisthal Algor ◽  
Anat Niztan ◽  
Sebastian Katz ◽  
Moshe Benhamou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Cell Death ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Early Passage ◽  
Systemic Injection ◽  
Rpe Cells

Oxidative stress leads to the degeneration of retinal pigment epithelial (RPE) and photoreceptor cells. We evaluated the potential of adipose-derived mesenchymal stem cells (ASCs) as a therapeutic tool by studying the migration capacity of ASCs in vitro and their protective effect against RPE cell death under oxidative stress in vitro and in vivo. ASCs exhibited enhanced migration when exposed to conditioned medium of oxidative stressed RPE cells obtained by hydrogen peroxide. Migration-related axis SDF-1/CXCR4 was studied, and upregulation of SDF-1 in stressed RPE and of CXCR4 in ASCs was detected. Moreover, ASCs’ conditioned medium prevented H2O2-induced cell death of RPE cells. Early passage ASCs had high expression level of HGF, low VEGF levels, and unmodulated IL-1β levels, compared to late passage ASCs. Thus, early passage ASCs show the potential to migrate towards damaged RPE cells and protect them in a paracrine manner from cell death induced by oxidative stress. In vivo, mice received systemic injection of NaIO3, and 72 h later, ASCs were transplanted in the subretinal space. Seven days after ASC transplantation, the eyes were enucleated fixed and frozen for immunohistochemical analysis. Under such conditions, ASC-treated mice showed preservation of nuclear layers in the outer nuclear layer and stronger staining of RPE and photoreceptor layer, compared to PBS-treated mice. Taken together, our results indicate that ASCs are able to home in on damaged RPE cells and protect against damage to the RPE and PR layers caused by oxidative stress. These data imply the potential that ASCs have in regenerating RPE under oxidative stress, providing the basis for a therapeutic approach to retinal degeneration diseases related to oxidative stress that could help save the eyesight of millions of people worldwide.

scholarly journals A Novel High-Throughput Technique for Identifying Monoclonal Antibodies capable of Death Receptor Induced Apoptosis

2009 ◽  
Vol 2 ◽  
pp. JCD.S3660
Author(s):  
Hang Fai Kwok ◽  
Julie A. Gormley ◽  
Christopher J. Scott ◽  
James A. Johnston ◽  
Shane A. Olwill
Keyword(s):  
Cell Death ◽  
High Throughput ◽  
High Throughput Screening ◽  
False Negative ◽  
Death Receptor ◽  
Annexin V ◽  
Fas Receptor ◽  
Induced Apoptosis

The study of death receptor family induced apoptosis has gained momentum in recent years with the knowledge that therapeutic antibodies targeting DR4 and DR5 (death receptor's 4 and 5) have proved efficacious in multiple clinical trials. The therapeutic rationale is based on targeting and amplifying a tumour tissues normal cell death programme (apoptosis). While advances in the targeting of DR4 and DR5 have been successful the search for an agonistic antibody to another family member, the Fas receptor, has proven more elusive. This is partly due to the differing in vitro and in vivo characteristics of individual antibodies. In order to induce Fas targeted cell death an antibody must be capable of binding to and trimerising the receptor. It has been shown that antibodies capable of performing this function in vivo, with the assistance of tumour associated cells, do not always induce apoptosis in vitro. As a result the use of current methodologies to detect functional antibodies in vitro may have dismissed potential therapeutic candidates ('false negative'). Here we report a novel high throughput screening technique which artificially cross-links antibodies bound to the Fas receptor. By combining this process with Annexin-V and Prodidium Iodide (PI) staining we can select for antibodies which have the potential to induce apoptosis in vivo.

The Kinase Inhibitor Sorafenib Can Disrupt the Survival Support Provided by the Microenvironment and Induce Apoptosis of Chronic Lymphocytic Leukemia Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 47-47
Author(s):  
Jessie-F Fecteau ◽  
Ila Bharati ◽  
Morgan O'Hayre ◽  
Tracy Handel ◽  
Thomas J. Kipps ◽  
...  
Keyword(s):  
Single Dose ◽  
Cell Viability ◽  
Cell Survival ◽  
Kinase Inhibitor ◽  
Vehicle Control ◽  
Lymphocytic Leukemia ◽  
Viable Cells ◽  
Induced Apoptosis

Abstract Abstract 47 Chronic Lymphocytic Leukemia (CLL) is characterized by an accumulation of mature monoclonal B cells in the blood, secondary lymphoid tissue, and marrow. Despite their accumulation in vivo, CLL cells undergo spontaneous apoptosis in vitro unless rescued by extrinsic factors derived from the leukemia-cell microenvironment. Monocyte-derived Nurse-Like Cells (NLCs) and Marrow Stromal Cells (MSCs), representing the leukemic microenvironment, have been show to sustain CLL cell survival and more importantly to protect CLL cells from drug-induced apoptosis in vitro and possibly in vivo. Such protective niches are thought to prevent current therapies from achieving complete remission in patients. Investigating the mechanism(s) by which cells from the microenvironment promote CLL cell survival, particularly the signaling pathways triggered, will allow for the identification of new therapeutic targets aiming to disrupt these protective interactions. NLCs and MSCs have been shown to produce the chemokine SDF-1 (CXCL12), which can enhance CLL cell survival. We recently found that ZAP-70+ aggressive CLL cells responded by an increased survival to this chemokine, compared to ZAP-70- indolent CLL cells, and that this response was accompanied by the activation of the ERK pathway. Attempting to abrogate this survival pathway, we found that sorafenib (BAY 43–9006, Nexavar) a multi-kinase inhibitor targeting among others Raf kinases and thereby the RAF/MEK/ERK pathway, strongly reduced CLL cell viability in a time and dose dependent manner. A regimen of one single dose of 10uM of sorafenib significantly reduced CLL cell viability to 18+/−10% cells after 48hrs compared to vehicle control (DMSO; 100%; n=5). The daily addition of 1uM sorafenib also significantly decreased CLL cell viability, leading to 31+/−21% and 11+/−5% viable cells after 6 and 7 days respectively, compared to DMSO (n=5). More importantly, our results show that sorafenib induces CLL cell death in the presence of NLCs and MSCs. A single dose of sorafenib (10uM) rapidly decreased the fraction of viable CLL cells overtime, passing from 40+/−16% after 1 day to 10+/−3% after 4 days (n=4) in the context of NLCs and to 25+/−3% after 2 days and 14+/−3% after 4 days in the presence of MSCs, when compared to vehicle control (>80%; n=4). In the presence of NLCs, the 1uM daily regimen also uncovered an increased sensitivity of ZAP-70+ CLL cells to this drug, reducing in 6 days their viability to 13+/−2% (n=4), which approximately half the fraction of viable cells remaining in the ZAP-70- group (40+/−16%; n=7). We next studied sorafenib-mediated cytotoxicity by investigating its impact on the expression of pro-survival molecules. We found that Mcl-1, Bcl-2 and Bcl-xL protein expression was reduced in CLL cells compared to vehicle control, when stimulated with CXCL12 (n=3). In the presence of NLCs and MSCs, only Mcl-1 expression was downregulated, which was also associated with a reduction of the active form of the transcription factor CREB, involved in Mcl-1 expression. Because Mcl-1 expression can be regulated by ERK and AKT pathways, we next investigated if they were abrogated by sorafenib. We indeed found that MEK, ERK, and AKT activation were reduced by this inhibitor compared to vehicle control (n=3). We therefore propose that the cytotoxic effect of sorafenib on CLL cells is due to its interference with at least these two major survival pathways. Since sorafenib caused apoptosis of CLL cells in context of the microenvironment, we reasoned that it might also cause apoptosis of chemotherapy resistant CLL cells. To test this hypothesis, we studied cells from fludarabine-refractory patients. In the presence of NLCs, a single dose of 10uM sorafenib induced a significant reduction in CLL cell viability after 2 days: only 4+/−2% viable cells remained compared to 78+/−12% for the vehicle control (n=4). A comparable observation was made in the presence of MSCs: sorafenib potently induced apoptosis, leaving 12+/−3% live cells after 2 days, compared to vehicle control (71+/−16%; n=4). These results are very promising as they suggest that sorafenib could be an effective novel therapeutic for CLL, affecting the viability of the leukemic cells even in protective niches. Since sorafenib has been approved by the FDA in 2007 for the treatment of advanced hepatocellular carcinoma, a pilot study is currently being planned at UCSD to evaluate the potential of this drug in CLL in vivo. Disclosures: No relevant conflicts of interest to declare.

scholarly journals DR5 Knockout Mice Are Compromised in Radiation-Induced Apoptosis

2005 ◽  
Vol 25 (5) ◽  
pp. 2000-2013 ◽  
Author(s):  
Niklas Finnberg ◽  
Joshua J. Gruber ◽  
Peiwen Fei ◽  
Dorothea Rudolph ◽  
Anka Bric ◽  
...  
Keyword(s):  
Cell Death ◽  
Null Mouse ◽  
Organ Specific ◽  
Radiation Induced ◽  
Induced Apoptosis ◽  
The Brain ◽  
Necrosis Factor

ABSTRACT DR5 (also called TRAIL receptor 2 and KILLER) is an apoptosis-inducing membrane receptor for tumor necrosis factor-related apoptosis-inducing ligand (also called TRAIL and Apo2 ligand). DR5 is a transcriptional target of p53, and its overexpression induces cell death in vitro. However, the in vivo biology of DR5 has remained largely unexplored. To better understand the role of DR5 in development and in adult tissues, we have created a knockout mouse lacking DR5. This mouse is viable and develops normally with the exception of having an enlarged thymus. We show that DR5 is not expressed in developing embryos but is present in the decidua and chorion early in development. DR5-null mouse embryo fibroblasts expressing E1A are resistant to treatment with TRAIL, suggesting that DR5 may be the primary proapoptotic receptor for TRAIL in the mouse. When exposed to ionizing radiation, DR5-null tissues exhibit reduced amounts of apoptosis compared to wild-type thymus, spleen, Peyer's patches, and the white matter of the brain. In the ileum, colon, and stomach, DR5 deficiency was associated with a subtle phenotype of radiation-induced cell death. These results indicate that DR5 has a limited role during embryogenesis and early stages of development but plays an organ-specific role in the response to DNA-damaging stimuli.

scholarly journals Molecular Imaging for Comparison of Different Growth Factors on Bone Marrow-Derived Mesenchymal Stromal Cells’ Survival and ProliferationIn Vivo

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hongyu Qiao ◽  
Ran Zhang ◽  
Lina Gao ◽  
Yanjie Guo ◽  
Jinda Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Bioluminescence Imaging ◽  
Firefly Luciferase ◽  
Control Group ◽  
Induced Apoptosis

Introduction. Bone marrow-derived mesenchymal stromal cells (BMSCs) have emerged as promising cell candidates but with poor survival after transplantation. This study was designed to investigate the efficacy of VEGF, bFGF, and IGF-1 on BMSCs’ viability and proliferation bothin vivoandin vitrousing bioluminescence imaging (BLI).Methods. BMSCs were isolated fromβ-actin-Fluc+transgenic FVB mice, which constitutively express firefly luciferase. Apoptosis was induced by hypoxia preconditioning for up to 24 h followed by flow cytometry and TUNEL assay. 106BMSCs with/without growth factors were injected subcutaneously into wild type FVB mice’s backs. Survival of BMSCs was longitudinally monitored using bioluminescence imaging (BLI) for 5 weeks. Protein expression of Akt, p-Akt, PARP, and caspase-3 was detected by Western blot.Results. Hypoxia-induced apoptosis was significantly attenuated by bFGF and IGF-1 compared with VEGF and control groupin vitro(P<0.05). When combined with matrigel, IGF-1 showed the most beneficial effects in protecting BMSCs from apoptosisin vivo.The phosphorylation of Akt had a higher ratio in the cells from IGF-1 group.Conclusion. IGF-1 could protect BMSCs from hypoxia-induced apoptosis through activation of p-Akt/Akt pathway.

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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