Resveratrol inhibits autophagy in HTR-8/SVneo model by alleviating trophoblast oxidative stress

Abstract BackgroundThe normal function of the placenta at each time stage of pregnancy is essential to a successful outcome. Placental dysfunction and increased oxidative stress and autophagy are the cause of a series of severe pregnancy complications. Resveratrol is a potent antioxidant that has shown beneficial effects in many diseases. We aim to investigate whether excessive autophagy is associated with oxidative stress in the trophoblast oxidative stress model. Resveratrol was taken to clarify its role in excessive autophagy of placental trophoblasts. MethodsWe established an in vitro model of oxidative stress by exposing the human first-trimester extravillous trophoblast cell line HTR-8/SVneo to H2O2. Levels of autophagy-related proteins (LC3, Beclin-1, p53 and mTOR) were detected by western blot.ResultsTreatment with resveratrol significantly ameliorated H2O2-induced cytotoxicity, morphological damage, oxidative stress and autophagy. Mechanistically, resveratrol restored the levels of autophagy-related proteins including LC3-II, Beclin-1 and p53, mTOR that were dysregulated by H2O2.ConclusionsResveratrol may protect human trophoblasts against H2O2-induced oxidative stress by reducing excessive autophagy, thus ensuring the normal biological functions of trophoblasts.

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HYPOXIA AND REPRODUCTIVE HEALTH: Oxygen and development of the human placenta

Reproduction ◽

10.1530/rep-20-0153 ◽

2021 ◽

Vol 161 (1) ◽

pp. F53-F65 ◽

Cited By ~ 2

Author(s):

Graham J Burton ◽

Tereza Cindrova-Davies ◽

Hong wa Yung ◽

Eric Jauniaux

Keyword(s):

Oxidative Stress ◽

Human Placenta ◽

Epithelial Mesenchymal Transition ◽

First Trimester ◽

Extravillous Trophoblast ◽

Low Oxygen ◽

Placental Development ◽

Mesenchymal Transition ◽

Oxygen Concentrations

Development of the human placenta takes place in contrasting oxygen concentrations at different stages of gestation, from ~20 mmHg during the first trimester rising to ~60 mmHg at the start of the second trimester before gradually declining to ~40 mmHg at term. In view of these changes, the early placenta has been described as ‘hypoxic’. However, placental metabolism is heavily glycolytic, supported by the rich supply of glucose from the endometrial glands, and there is no evidence of energy compromise. On the contrary, the trophoblast is highly proliferative, with the physiological low-oxygen environment promoting maintenance of stemness in progenitor populations. These conditions favour the formation of the cytotrophoblastic shell that encapsulates the conceptus and interfaces with the endometrium. Extravillous trophoblast cells on the outer surface of the shell undergo an epithelial-mesenchymal transition and acquire invasive potential. Experimental evidence suggests that these changes may be mediated by the higher oxygen concentration present within the placental bed. Interpreting in vitro data is often difficult, however, due to the use of non-physiological oxygen concentrations and trophoblast-like cell lines or explant models. Trophoblast is more vulnerable to hyperoxia or fluctuating levels of oxygen than to hypoxia, and some degree of placental oxidative stress likely occurs in all pregnancies towards term. In complications of pregnancy, such as early-onset pre-eclampsia, malperfusion generates high levels of oxidative stress, causing release of factors that precipitate the maternal syndrome. Further experiments are required using genuine trophoblast progenitor cells and physiological concentrations to fully elucidate the pathways by which oxygen regulates placental development.

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Impact of Polyphenolic-Food on Longevity: An Elixir of Life. An Overview

Antioxidants ◽

10.3390/antiox10040507 ◽

2021 ◽

Vol 10 (4) ◽

pp. 507

Author(s):

Rosaria Meccariello ◽

Stefania D’Angelo

Keyword(s):

Oxidative Stress ◽

Food Sources ◽

Preventive Action ◽

Nutritional Interventions ◽

Beneficial Effects ◽

Age Related ◽

Macromolecular Damage ◽

And Oxidative Stress

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.

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Estimation of the Genotoxicityof Hydrogen Peroxide and Antioxidant Actionof Halo Acid by the Method of Dna-Cometwith the Use of the Model of Transplantable Cell Cultures

Vestnik Volgogradskogo Gosudarstvennogo Universiteta Serija 11 Estestvennye nauki ◽

10.15688/jvolsu11.2018.1.7 ◽

2018 ◽

pp. 40-43

Author(s):

Olga Verle ◽

Oleg Ostrovskiy ◽

Valerian Verovskiy ◽

Galina Dudchenko

Keyword(s):

Oxidative Stress ◽

Hydrogen Peroxide ◽

In Vitro Model ◽

Cell Damage ◽

Protective Action ◽

Genetic Material ◽

Optimal Level ◽

Pharmacological Agents ◽

Vitro Model

In the framework of the study, the degree of defragmentation of DNA by the DNA-comet method is evaluated when exposed to the cell culture of hydrogen peroxide (H2O2), and an in vitro model is developed to evaluate the antioxidant activity of new pharmacological agents. The results of working with cell lines show that the percentage of damage to the genetic material of cells of intact samples does not greatly vary from the method of removing the cellular monolayer from the culture plastic. Concerning the effect of H2O2 as an inducer of oxidative stress on DNA cell damage, the optimal level of DNA defragmentation has been modeled for subsequent studies of the protective action of antioxidants.

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Baboon placental heparin-binding epidermal growth factor-like growth factor

Reproduction ◽

10.1530/rep-19-0487 ◽

2020 ◽

Vol 160 (1) ◽

pp. 31-37

Author(s):

D Randall Armant ◽

Graham W Aberdeen ◽

Brian A Kilburn ◽

Gerald J Pepe ◽

Eugene D Albrecht

Keyword(s):

Growth Factor ◽

First Trimester ◽

Extravillous Trophoblast ◽

Immunocytochemical Staining ◽

Heparin Binding ◽

Spiral Artery ◽

Primate Model ◽

Artery Remodeling ◽

Egf Family

Placental extravillous trophoblast remodeling of the uterine spiral arteries is important for promoting blood flow to the placenta and fetal development. Heparin-binding EGF-like growth factor (HB-EGF), an EGF family member, stimulates differentiation and invasive capacity of extravillous trophoblasts in vitro. Trophoblast expression and maternal levels of HB-EGF are reduced at term in women with preeclampsia, but it is uncertain whether HB-EGF is downregulated earlier when it may contribute to placental insufficiency. A nonhuman primate model has been established in which trophoblast remodeling of the uterine spiral arteries is suppressed by shifting the rise in estrogen from the second to the first trimester of baboon pregnancy. In the present study, we used this model to determine if placental HB-EGF is altered by prematurely elevating estrogen early in baboon gestation. Uterine spiral artery remodeling and placental expression of HB-EGF and other EGF family members were assessed on day 60 of gestation in baboons treated with estradiol (E2) daily between days 25 and 59 of gestation (term = 184 days). The percentages of spiral artery remodeling were 90, 84 and 70% lower (P < 0.01), respectively, for vessels of 26–50, 51–100 and >100 µm diameter in E2-treated compared with untreated baboons. HB-EGF protein quantified by immunocytochemical staining/image analysis was decreased three-fold (P < 0.01) in the placenta of E2-treated versus untreated baboons, while amphiregulin (AREG) and EGF expression was unaltered. Therefore, we propose that HB-EGF modulates the estrogen-sensitive remodeling of the uterine spiral arteries by the extravillous trophoblast in early baboon pregnancy.

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Therapeutic Effect of Camel Milk and Its Exosomes on MCF7 Cells In Vitro and In Vivo

Integrative Cancer Therapies ◽

10.1177/1534735418786000 ◽

2018 ◽

Vol 17 (4) ◽

pp. 1235-1246 ◽

Cited By ~ 27

Author(s):

Abdelnaser A. Badawy ◽

Mohammed A. El-Magd ◽

Sana A. AlSadrah

Keyword(s):

Oxidative Stress ◽

Gene Expression ◽

Immune Response ◽

Local Injection ◽

Camel Milk ◽

Anticancer Effect ◽

Mcf7 Cells ◽

Beneficial Effects

Background/Objectives: In the Middle East, people consume camel milk regularly as it is believed to improve immunity against diseases and decrease the risk for cancer. Recently, it was noted that most of the beneficial effects of milk come from their nanoparticles, especially exosomes. Herein, we evaluated the anticancer potential of camel milk and its exosomes on MCF7 breast cancer cells (in vitro and in vivo) and investigated the possible underlying molecular mechanism of action. Methods/Results: Administration of camel milk (orally) and its exosomes (orally and by local injection) decreased breast tumor progression as evident by ( a) higher apoptosis (indicated by higher DNA fragmentation, caspase-3 activity, Bax gene expression, and lower Bcl2 gene expression), ( b) remarkable inhibition of oxidative stress (decrease in MDA levels and iNOS gene expression); ( c) induction of antioxidant status (increased activities of SOD, CAT, and GPX), ( d) notable reduction in expression of inflammation-( IL1b, NFκB), angiogenesis-( VEGF) and metastasis-( MMP9, ICAM1) related genes; and ( e) higher immune response (high number of CD+4, CD+8, NK1.1 T cells in spleen). Conclusions: Overall, administration of camel milk–derived exosomes showed better anticancer effect, but less immune response, than treatment by camel milk. Moreover, local injection of exosomes led to better improvement than oral administration. These findings suggest that camel milk and its exosomes have anticancer effect possibly through induction of apoptosis and inhibition of oxidative stress, inflammation, angiogenesis and metastasis in the tumor microenvironment. Thus, camel milk and its exosomes could be used as an anticancer agent for cancer treatment.

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Abstract 246: Human Induced Pluripotent Stem Cells Reveal Mitophagy as an Essential Process Against Diabetic Cardiomyopathy

Circulation Research ◽

10.1161/res.117.suppl_1.246 ◽

2015 ◽

Vol 117 (suppl_1) ◽

Author(s):

Sang-Ging Ong ◽

Won Hee Lee ◽

Kazuki Kodo ◽

Haodi Wu ◽

Joseph C Wu

Keyword(s):

Oxidative Stress ◽

Diabetic Cardiomyopathy ◽

Mitochondrial Fission ◽

Induced Pluripotent Stem Cell ◽

Mitochondrial Fragmentation ◽

Normal Cells ◽

Mitochondrial Pathology ◽

Vitro Model ◽

Induced Pluripotent

Diabetic cardiomyopathy is a common consequence of diabetes and associated with mitochondrial pathology. Using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) as an in vitro model of diabetes, we sought to understand the role of mitophagy, a process that selectively degrades mitochondria through the autophagy-lysosome pathway as a crucial quality control pathway against diabetic cardiomyopathy. We first showed that iPSC-CMs exposed to a diabetic milieu demonstrated increased hypertrophy, impaired calcium signaling, and higher oxidative stress. Flow cytometry analysis of iPSC-CMs subjected to diabetic conditions revealed two distinct population of cells (normal and hypertrophied), suggesting a heterogeneous response to hyperglycemia. In these cells, hypertrophied iPSC-CMs were found to have reduced mitophagy compared to normal cells when exposed to hyperglycemia. In addition, we showed that mitochondrial fragmentation was also decreased in the hypertrophied iPSC-CMs compared to normal cells upon exposure to hyperglycemia, demonstrating a link between mitochondrial fragmentation and mitophagy. Surprisingly, pretreatment of iPSC-CMs with a non-selective antioxidant, N-(2-mercaptopropionyl)-glycine, not only failed to limit the deleterious effects of hyperglycemia, but actually led to increased hypertrophy and cell death. We found that mitophagy was significantly reduced in iPSC-CMs following antioxidant treatment, suggesting the need of mild oxidative stress as a trigger for mitophagy. Future studies are warranted to further investigate the association between oxidative stress, mitochondrial fragmentation, and mitochondrial fission as targets against diabetic cardiomyopathy.

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Hydrogen Peroxide-Preconditioned Human Adipose-Derived Stem Cells Enhance the Recovery of Oligodendrocyte-Like Cells after Oxidative Stress-Induced Damage

International Journal of Molecular Sciences ◽

10.3390/ijms21249513 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9513

Author(s):

Patricia Garrido-Pascual ◽

Ana Alonso-Varona ◽

Begoña Castro ◽

María Burón ◽

Teodoro Palomares

Keyword(s):

Oxidative Stress ◽

Stem Cells ◽

Therapeutic Potential ◽

Mild Stress ◽

Adipose Derived Stem Cells ◽

Vitro Model ◽

Novel Strategy ◽

The One ◽

Cell Conditioned Medium

Oxidative stress associated with neuroinflammation is a key process involved in the pathophysiology of neurodegenerative diseases, and therefore, has been proposed as a crucial target for new therapies. Recently, the therapeutic potential of human adipose-derived stem cells (hASCs) has been investigated as a novel strategy for neuroprotection. These cells can be preconditioned by exposing them to mild stress in order to improve their response to oxidative stress. In this study, we evaluate the therapeutic potential of hASCs preconditioned with low doses of H2O2 (called HC016 cells) to overcome the deleterious effect of oxidative stress in an in vitro model of oligodendrocyte-like cells (HOGd), through two strategies: i, the culture of oxidized HOGd with HC016 cell-conditioned medium (CM), and ii, the indirect co-culture of oxidized HOGd with HC016 cells, which had or had not been exposed to oxidative stress. The results demonstrated that both strategies had reparative effects, oxidized HC016 cell co-culture being the one associated with the greatest recovery of the damaged HOGd, increasing their viability, reducing their intracellular reactive oxygen species levels and promoting their antioxidant capacity. Taken together, these findings support the view that HC016 cells, given their reparative capacity, might be considered an important breakthrough in cell-based therapies.

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Cpt1a promoted ROS-induced oxidative stress and inflammation in liver injury via the Nrf2/HO-1 and NLRP3 inflammasome signaling pathway

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2020-0165 ◽

2020 ◽

Author(s):

Xigang Luo ◽

Dapeng Sun ◽

Yinxiang Wang ◽

Fengxiang Zhang ◽

Yi Wang

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Signaling Pathway ◽

Nlrp3 Inflammasome ◽

Receptor Protein ◽

Heme Oxygenase 1 ◽

Related Factor ◽

Over Expression ◽

Vitro Model

Various liver diseases caused by liver damage seriously affect people’s health. The purpose of this study was to clarify that the effects and mechanism of Carnitine palmitoyltransferase 1 (Cpt1a) on oxidative stress and inflammation in liver injury. It was found that the expression of Cpt1a mRNA was up-regulated in model mice of liver injury. So, over-expression of Cpt1a increased reactive oxygen species (ROS) production and malondialdehyde (MDA) levels, and reduced superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-px) levels in vitro model of liver injury. It was also shown that over-expression of Cpt1a suppressed the Nuclear factor-erythroid-2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) signaling pathway. In summary, these data indicate that Cpt1a promotes ROS-induced oxidative stress in liver injury via the Nrf2/HO-1 and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome signaling pathway.

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Effect of Borrelia burgdorferi Outer Membrane Vesicles on Host Oxidative Stress Response

Antibiotics ◽

10.3390/antibiotics9050275 ◽

2020 ◽

Vol 9 (5) ◽

pp. 275

Author(s):

Keith Wawrzeniak ◽

Gauri Gaur ◽

Eva Sapi ◽

Alireza G. Senejani

Keyword(s):

Oxidative Stress ◽

Borrelia Burgdorferi ◽

Outer Membrane ◽

Neuroblastoma Cells ◽

Membrane Vesicles ◽

Antioxidant Response ◽

Outer Membrane Vesicles ◽

Vitro Model ◽

Superoxide Dismutase 2

Outer membrane vesicles (OMVs) are spherical bodies containing proteins and nucleic acids that are released by Gram-negative bacteria, including Borrelia burgdorferi, the causative agent of Lyme disease. The functional relationship between B. burgdorferi OMVs and host neuron homeostasis is not well understood. The objective of this study was to examine how B. burgdorferi OMVs impact the host cell environment. First, an in vitro model was established by co-culturing human BE2C neuroblastoma cells with B. burgdorferi B31. B. burgdorferi was able to invade BE2C cells within 24 h. Despite internalization, BE2C cell viability and levels of apoptosis remained unchanged, but resulted in dramatically increased production of MCP-1 and MCP-2 cytokines. Elevated secretion of MCP-1 has previously been associated with changes in oxidative stress. BE2C cell mitochondrial superoxides were reduced as early as 30 min after exposure to B. burgdorferi and OMVs. To rule out whether BE2C cell antioxidant response is the cause of decline in superoxides, superoxide dismutase 2 (SOD2) gene expression was assessed. SOD2 expression was reduced upon exposure to B. burgdorferi, suggesting that B. burgdorferi might be responsible for superoxide reduction. These results suggest that B. burgdorferi modulates cell antioxidant defense and immune system reaction in response to the bacterial infection. In summary, these results show that B. burgdorferi OMVs serve to directly counter superoxide production in BE2C neurons, thereby ‘priming’ the host environment to support B. burgdorferi colonization.

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