scholarly journals Unbiased in vivo exploration of nuclear bodies-enhanced sumoylation reveals that PML orchestrates embryonic stem cell fate

2021 ◽  
Author(s):  
Sarah Tessier ◽  
Omar Ferhi ◽  
Marie-Claude Geoffroy ◽  
Roman Gonzalez-Prieto ◽  
Antoine Canat ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Fate ◽  
Stress Responses ◽  
Embryonic Stem ◽  
Nuclear Bodies ◽  
Metabolic Adaptation ◽  
Stem Cell Fate ◽  
Protective Environment ◽  
And Oxidative Stress

Membrane-less organelles are condensates formed by phase separation whose functions often remain enigmatic. Upon oxidative stress, PML scaffolds Nuclear Bodies (NBs) to regulate senescence or metabolic adaptation, but their role in pluripotency remains elusive. Here we establish that PML is required for basal SUMO2/3 conjugation in mESCs and oxidative stress-driven sumoylation in mESCs or in vivo. PML NBs create an oxidation-protective environment for UBC9-driven SUMO2/3 conjugation of PML partners, often followed by their poly-ubiquitination and degradation. Differential in vivo proteomics identified several members of the KAP1 complex as PML NB-dependent SUMO2-targets. The latter drives functional activation of this key epigenetic repressor. Accordingly, Pml-/- mESCs re-express transposable elements and display features of totipotent-like cells, a process further enforced by PML-controlled SUMO2-conjugation of DPPA2. Finally, PML is required for adaptive stress responses in mESCs. Collectively, PML orchestrates mESC fate through SUMO2-conjugation of key transcriptional or epigenetic regulators, raising new mechanistic hypotheses about PML roles in normal or cancer stem cells.

scholarly journals Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma

2021 ◽  
Author(s):  
Sinan Xiong ◽  
Wee-Joo Chng ◽  
Jianbiao Zhou
Keyword(s):  
Oxidative Stress ◽  
Multiple Myeloma ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cell Fate ◽  
Stress Responses ◽  
Plasma Cells ◽  
Reactive Oxygen Species Generation ◽  
Future Research ◽  
And Oxidative Stress

AbstractUnder physiological and pathological conditions, cells activate the unfolded protein response (UPR) to deal with the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum. Multiple myeloma (MM) is a hematological malignancy arising from immunoglobulin-secreting plasma cells. MM cells are subject to continual ER stress and highly dependent on the UPR signaling activation due to overproduction of paraproteins. Mounting evidence suggests the close linkage between ER stress and oxidative stress, demonstrated by overlapping signaling pathways and inter-organelle communication pivotal to cell fate decision. Imbalance of intracellular homeostasis can lead to deranged control of cellular functions and engage apoptosis due to mutual activation between ER stress and reactive oxygen species generation through a self-perpetuating cycle. Here, we present accumulating evidence showing the interactive roles of redox homeostasis and proteostasis in MM pathogenesis and drug resistance, which would be helpful in elucidating the still underdefined molecular pathways linking ER stress and oxidative stress in MM. Lastly, we highlight future research directions in the development of anti-myeloma therapy, focusing particularly on targeting redox signaling and ER stress responses.

scholarly journals 8-Methoxypsoralen has Anti-inflammatory and Antioxidant Roles in Osteoarthritis Through SIRT1/NF-κB Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Jichao Li ◽  
Zeng Zhang ◽  
Jinan Qiu ◽  
Xiaohan Huang
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Stress Responses ◽  
Pain Threshold ◽  
Stress Factors ◽  
Protective Effects ◽  
Inhibition Of Proliferation ◽  
Oxidative Stress Responses ◽  
And Oxidative Stress

Osteoarthritis (OA) is mainly manifested by joint pain, stiffness and mobility disorder, which is the main cause of pain and disability in middle-aged and elderly people. In this study, we aimed to explore the role and mechanism of 8-Methoxypsoralen (8-MOP) in the OA model both in vitro and in vivo. The rat chondrocytes were treated with IL-1β, and the proliferation, apoptosis, inflammatory reactions and oxidative stress responses were determined after treatment with different concentrations of 8-MOP. Real-time quantitative polymerase chain reaction (qRT-PCR) and/or Western blot were implemented to check the AMPK/SIRT1/NF-κB expression in chondrocytes. The NF-κB activity was determined by dual luciferase experiment. The pain threshold of OA rat model dealt with 8-MOP and/or the SIRT1 inhibitor EX527 was measured. Our results revealed that 8-MOP evidently reduced IL-1β-mediated apoptosis and inhibition of proliferation, and mitigated the expression of inflammatory cytokines and oxidative stress factors in chondrocytes. Additionally, 8-MOP promoted phosphorylated level of AMPKα, enhanced SIRT1 expression and inhibited the phosphorylation of NF-κB. After treatment with EX527, 8-MOP-mediated protective effects on chondrocytes were mostly reversed. In vivo, 8-MOP obviously improved the pain threshold in the OA rat model and reduced the injury and apoptosis of chondrocytes in the joints. In addition, 8-MOP relieved inflammatory and oxidative stress responses in the articular cartilage via enhancing SIRT1 and repressing NF-κB activation. After the treatment with EX527, the 8-MOP-mediated protective effects were distinctly weakened. In summary, our study testified that 8-MOP alleviates pain, inflammatory and oxidative stress responses in OA rats through the SIRT1/NF-κB pathway, which is expected to become a new reagent for clinical treatment of OA.

scholarly journals The human hepatocyte TXG-MAPr: gene co-expression network modules to support mechanism-based risk assessment

2021 ◽  
Author(s):  
Giulia Callegaro ◽  
Steven J. Kunnen ◽  
Panuwat Trairatphisan ◽  
Solène Grosdidier ◽  
Marije Niemeijer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Risk Assessment ◽  
Stress Responses ◽  
Safety Testing ◽  
Support Mechanism ◽  
Mechanisms Of Toxicity ◽  
R Shiny ◽  
Promising Source ◽  
And Oxidative Stress

AbstractMechanism-based risk assessment is urged to advance and fully permeate into current safety assessment practices, possibly at early phases of drug safety testing. Toxicogenomics is a promising source of mechanisms-revealing data, but interpretative analysis tools specific for the testing systems (e.g. hepatocytes) are lacking. In this study, we present the TXG-MAPr webtool (available at https://txg-mapr.eu/WGCNA_PHH/TGGATEs_PHH/), an R-Shiny-based implementation of weighted gene co-expression network analysis (WGCNA) obtained from the Primary Human Hepatocytes (PHH) TG-GATEs dataset. The 398 gene co-expression networks (modules) were annotated with functional information (pathway enrichment, transcription factor) to reveal their mechanistic interpretation. Several well-known stress response pathways were captured in the modules, were perturbed by specific stressors and showed preservation in rat systems (rat primary hepatocytes and rat in vivo liver), with the exception of DNA damage and oxidative stress responses. A subset of 87 well-annotated and preserved modules was used to evaluate mechanisms of toxicity of endoplasmic reticulum (ER) stress and oxidative stress inducers, including cyclosporine A, tunicamycin and acetaminophen. In addition, module responses can be calculated from external datasets obtained with different hepatocyte cells and platforms, including targeted RNA-seq data, therefore, imputing biological responses from a limited gene set. As another application, donors’ sensitivity towards tunicamycin was investigated with the TXG-MAPr, identifying higher basal level of intrinsic immune response in donors with pre-existing liver pathology. In conclusion, we demonstrated that gene co-expression analysis coupled to an interactive visualization environment, the TXG-MAPr, is a promising approach to achieve mechanistic relevant, cross-species and cross-platform evaluation of toxicogenomic data.

Repressive effect of Rhus coriaria L. fruit extracts on microglial cells-mediated inflammatory and oxidative stress responses

2021 ◽  
Vol 269 ◽  
pp. 113748
Author(s):  
Mohamad Khalil ◽  
Ali Bazzi ◽  
Dana Zeineddine ◽  
Wissam Jomaa ◽  
Ahmad Daher ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
Microglial Cells ◽  
Fruit Extracts ◽  
Repressive Effect ◽  
Rhus Coriaria ◽  
Oxidative Stress Responses ◽  
And Oxidative Stress

scholarly journals Canthin-6-one ameliorates TNBS-induced colitis in rats by modulating inflammation and oxidative stress. An in vivo and in silico approach

2021 ◽  
Vol 186 ◽  
pp. 114490
Author(s):  
Karuppusamy Arunachalam ◽  
Amilcar Sabino Damazo ◽  
Antonio Macho ◽  
Monica Steffi Matchado ◽  
Eduarda Pavan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Silico ◽  
And Oxidative Stress

Oxidative stress sensing and response in neural stem cell fate

2021 ◽  
Vol 169 ◽  
pp. 74-83
Author(s):  
Inah Hwang ◽  
Deanna Tang ◽  
Jihye Paik
Keyword(s):  
Oxidative Stress ◽  
Stem Cell ◽  
Cell Fate ◽  
Neural Stem Cell ◽  
Stem Cell Fate ◽  
Stress Sensing

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

Antioxidants ◽  
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.

Pirfenidone mediates cigarette smoke extract induced inflammation and oxidative stress in vitro and in vivo

2021 ◽  
Vol 96 ◽  
pp. 107593
Author(s):  
Yiming Ma ◽  
Lijuan Luo ◽  
Xiangming Liu ◽  
Herui Li ◽  
Zihang Zeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Cigarette Smoke Extract ◽  
And Oxidative Stress

scholarly journals Imaging of redox-imbalance and oxidative stress in kidney in vivo, induced by dietary cholesterol

2019 ◽  
Vol 33 (1) ◽  
pp. 294-301
Author(s):  
Dessislava Lazarova ◽  
Sayaka Shibata ◽  
Itsuko Ishii ◽  
Genoveva Zlateva ◽  
Zhivko Zhelev ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dietary Cholesterol ◽  
Redox Imbalance ◽  
And Oxidative Stress
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