scholarly journals PARP-1 activation after oxidative insult promotes energy stress-dependent phosphorylation of YAP1 and reduces cell viability

2020 ◽  
Vol 477 (23) ◽  
pp. 4491-4513
Author(s):  
Sandra M. Martín-Guerrero ◽  
Pedro Casado ◽  
Maruan Hijazi ◽  
Vinothini Rajeeve ◽  
Julio Plaza-Díaz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Cell Viability ◽  
Stress Responses ◽  
H2o2 Treatment ◽  
Oxidative Treatment ◽  
Energy Stress ◽  
Cellular Stress Responses ◽  
Stress Dependent ◽  
Parp 1

Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that catalyze the transfer of ADP-ribose units from NAD+ to several target proteins involved in cellular stress responses. Using WRL68 (HeLa derivate) cells, we previously showed that PARP-1 activation induced by oxidative stress after H2O2 treatment lead to depletion of cellular NAD+ and ATP, which promoted cell death. In this work, LC–MS/MS-based phosphoproteomics in WRL68 cells showed that the oxidative damage induced by H2O2 increased the phosphorylation of YAP1, a transcriptional co-activator involved in cell survival, and modified the phosphorylation of other proteins involved in transcription. Genetic or pharmacological inhibition of PARP-1 in H2O2-treated cells reduced YAP1 phosphorylation and degradation and increased cell viability. YAP1 silencing abrogated the protective effect of PARP-1 inhibition, indicating that YAP1 is important for the survival of WRL68 cells exposed to oxidative damage. Supplementation of NAD+ also reduced YAP1 phosphorylation, suggesting that the loss of cellular NAD+ caused by PARP-1 activation after oxidative treatment is responsible for the phosphorylation of YAP1. Finally, PARP-1 silencing after oxidative treatment diminished the activation of the metabolic sensor AMPK. Since NAD+ supplementation reduced the phosphorylation of some AMPK substrates, we hypothesized that the loss of cellular NAD+ after PARP-1 activation may induce an energy stress that activates AMPK. In summary, we showed a new crucial role of PARP-1 in the response to oxidative stress in which PARP-1 activation reduced cell viability by promoting the phosphorylation and degradation of YAP1 through a mechanism that involves the depletion of NAD+.

scholarly journals Distinct stress-dependent signatures of cellular and extracellular tRNA-derived small RNAs (tDRs)

2021 ◽  
Author(s):  
Guoping Li ◽  
Aidan Manning ◽  
Alex Bagi ◽  
Xinyu Yang ◽  
Jonathan Howard ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
Small Rnas ◽  
Cellular Stress ◽  
Fragmentation Pattern ◽  
Cellular Models ◽  
Nutritional Deprivation ◽  
Cellular Stress Responses ◽  
Stress Dependent ◽  
And Oxidative Stress

The cellular response to stress is an important determinant of disease pathogenesis. Uncovering the molecular fingerprints of distinct stress responses may yield novel biomarkers for different diseases, and potentially identify key signaling pathways important for disease progression. tRNAs and tRNA-derived small RNAs (tDRs) comprise one of the most abundant RNA species in cells and have been associated with cellular stress responses. The presence of RNA modifications on tDRs has been an obstacle for accurately identifying tDRs with conventional small RNA sequencing. Here, we use AlkB-facilitated methylation sequencing (ARM-seq) to uncover a comprehensive landscape of cellular and extracellular tDR expression in a variety of human and rat cells during common stress responses, including nutritional deprivation, hypoxia, and oxidative stress. We found that extracellular tDRs have a distinct fragmentation signature with a predominant length of 31-33 nts and a highly specific termination position when compared with intracellular tDRs. Importantly, we found these signatures are better discriminators of different cellular stress responses compared to extracellular miRNAs. Distinct extracellular tDR signatures for each profiled stressor are elucidated in four different types of cells. This distinct extracellular tDR fragmentation pattern is also noted in plasma extracellular RNAs from patients on cardiopulmonary bypass. The observed overlap of these patient tDR signatures with the signatures of nutritional deprivation and oxidative stress in our cellular models provides preliminary in vivo corroboration of our findings and demonstrates the potential to establish novel extracellular tDR biomarkers in human disease models.

scholarly journals Identification of Toxicity Parameters Associated with Combustion Produced Soot Surface Chemistry and Particle Structure by in Vitro Assays

Biomedicines ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 345
Author(s):  
Heba Al Housseiny ◽  
Madhu Singh ◽  
Shaneeka Emile ◽  
Marvin Nicoleau ◽  
Randy L. Vander Wal ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Surface Chemistry ◽  
Cell Viability ◽  
Health Effects ◽  
Stress Responses ◽  
Surface Composition ◽  
Particle Surface ◽  
In Vitro Assays ◽  
Epithelial Cell Line ◽  
And Oxidative Stress

Air pollution has become the world’s single biggest environmental health risk of the past decade, causing millions of yearly deaths worldwide. One of the dominant air pollutants is fine particulate matter (PM2.5), which is a product of combustion. Exposure to PM2.5 has been associated with decreased lung function, impaired immunity, and exacerbations of lung disease. Accumulating evidence suggests that many of the adverse health effects of PM2.5 exposure are associated with lung inflammation and oxidative stress. While the physical structure and surface chemistry of PM2.5 are surrogate measures of particle oxidative potential, little is known about their contributions to negative health effects. In this study, we used functionalized carbon black particles as surrogates for atmospherically aged combustion-formed soot to assess the effects of PM2.5 surface chemistry in lung cells. We exposed the BEAS-2B lung epithelial cell line to different soot at a range of concentrations and assessed cell viability, inflammation, and oxidative stress. Our results indicate that exposure to soot with varying particle surface composition results in differential cell viability rates, the expression of pro-inflammatory and oxidative stress genes, and protein carbonylation. We conclude that particle surface chemistry, specifically oxygen content, in soot modulates lung cell inflammatory and oxidative stress responses.

scholarly journals PRDX6 Protects ARPE-19 Cells from Oxidative Damage via PI3K/AKT Signaling

2015 ◽  
Vol 36 (6) ◽  
pp. 2217-2228 ◽  
Author(s):  
Xu Zha ◽  
Guojiu Wu ◽  
Xueying Zhao ◽  
Liqiong Zhou ◽  
Hong Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Blue Light ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Annexin V ◽  
Retinal Disease ◽  
Akt Signaling ◽  
The Body ◽  
H2o2 Treatment

Background/Aims: Oxidative stress that damages cells of the retinal pigment epithelium (RPE) can cause the development of hereditary retinal disease (HRD). PRDX6, which is a member of the PRDX family, is essential for removing metabolic free radicals from the body. However, the effect of PRDX6 on oxidative stress in HRD remains unknown. In this study, we sought to investigate the role of PRDX6 in oxidative stress-induced HRD in ARPE-19 cells and the molecular mechanism involved. Methods: ARPE-19 cells were used in the current study. Intracellular ROS levels were determined by flow cytometry. Lipid peroxidation was measured using a commercial MDA assay kit. Cellular variability was determined by MTT assay. Apoptosis was determined using an Annexin V-FITC Apoptosis Detection Kit. mRNA and protein expression levels were detected by real-time PCR and western blot analysis, respectively. Results: We found that H2O2 and blue light could induce significant oxidative stress damage and cell death in ARPE-19 cells. Furthermore, we found that PRDX6 levels significantly decreased after H2O2 treatment. PRDX6 overexpression protected ARPE-19 cells from H2O2- and blue light-induced oxidative damage, while PRDX6 knockdown enhanced oxidative damage in these cells. Mechanistically, we found that PRDX6 prevented oxidative damage and promoted ARPE-19 cell survival through the PI3K/AKT signaling pathway. Conclusions: Collectively, these results suggest that PRDX6 protects ARPE-19 cells from H2O2-induced oxidative stress and apoptosis and that this protection is mediated at least partially through the PI3K/AKT pathway.

scholarly journals Heme Oxygenase-1-Mediated Autophagy Protects against Oxidative Damage in Rat Nucleus Pulposus-Derived Mesenchymal Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Sheng Chen ◽  
Sheng Liu ◽  
Lei Zhao ◽  
Hui Lin ◽  
Kaige Ma ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Cell Viability ◽  
Nucleus Pulposus ◽  
Heme Oxygenase ◽  
Early Stage ◽  
Underlying Mechanism ◽  
Research Direction ◽  
Heme Oxygenase 1 ◽  
Ivd Degeneration

Although endogenous nucleus pulposus-derived mesenchymal stem cell- (NPMSC-) based regenerative medicine has provided promising repair strategy for intervertebral disc (IVD) degeneration, the hostile microenvironments in IVD, including oxidative stress, can negatively affect the survival and function of the NPMSCs and severely hinder the endogenous repair process. Therefore, it is of great importance to reveal the mechanisms of the endogenous repair failure caused by the adverse microenvironments in IVD. The aim of this study was to investigate the effect of oxidative stress on the rat NPMSCs and its underlying mechanism. Our results demonstrated that oxidative stress inhibited cell viability, induced apoptosis, and increased the production of reactive oxygen species (ROS) in NPMSCs. In addition, the results showed that the expression level of heme oxygenase-1 (HO-1) increased at an early stage but decreased at a late stage when NPMSCs were exposed to oxidative stress, and the oxidative damages of NPMSCs could be partially reversed by promoting the expression of HO-1. Further mechanistic analysis indicated that the protective effect of HO-1 against oxidative damage in NPMSCs was mediated by the activation of autophagy. Taken together, our study revealed that oxidative stress could inhibit cell viability, induce apoptosis, and increase ROS production in NPMSCs, and HO-1-mediated autophagy might act as a protective response to the oxidative damage. These findings might enhance our understanding on the mechanism of the endogenous repair failure during IVD degeneration and provide novel research direction for the endogenous repair of IVD degeneration.

scholarly journals Panax Quinquefolius Saponin of Stem and Leaf Attenuates Intermittent High Glucose-Induced Oxidative Stress Injury in Cultured Human Umbilical Vein Endothelial Cells via PI3K/Akt/GSK-3βPathway

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jingshang Wang ◽  
Huijun Yin ◽  
Ye Huang ◽  
Chunyu Guo ◽  
Chengdong Xia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Oxidative Damage ◽  
Cell Viability ◽  
High Glucose ◽  
Umbilical Vein ◽  
Panax Quinquefolius ◽  
Stress Injury ◽  
Intermittent High Glucose ◽  
Umbilical Vein Endothelial Cells

Panax quinquefolius saponin of stem and leaf (PQS), the effective parts of American ginseng, is widely used in China as a folk medicine for diabetes and cardiovascular diseases treatment. In our previous studies, we have demonstrated that PQS could improve the endothelial function of type II diabetes mellitus (T2DM) rats with high glucose fluctuation. In the present study, we investigated the protective effects of PQS against intermittent high glucose-induced oxidative damage on human umbilical vein endothelial cells (HUVECs) and the role of phosphatidylinositol 3-kinase kinase (PI3K)/Akt/GSK-3βpathway involved. Our results suggested that exposure of HUVECs to a high glucose concentration for 8 days showed a great decrease in cell viability accompanied by marked MDA content increase and SOD activity decrease. Moreover, high glucose significantly reduced the phosphorylation of Akt and GSK-3β. More importantly, these effects were even more evident in intermittent high glucose condition. PQS treatment significantly attenuated intermittent high glucose-induced oxidative damage on HUVECs and meanwhile increased cell viability and phosphorylation of Akt and GSK-3βof HUVECs. Interestingly, all these reverse effects of PQS on intermittent high glucose-cultured HUVECs were inhibited by PI3K inhibitor LY294002. These findings suggest that PQS attenuates intermittent-high-glucose-induced oxidative stress injury in HUVECs by PI3K/Akt/GSK-3βpathway.

scholarly journals Multiple Pathways Differentially Regulate Global Oxidative Stress Responses in Fission Yeast

2008 ◽  
Vol 19 (1) ◽  
pp. 308-317 ◽  
Author(s):  
Dongrong Chen ◽  
Caroline R.M. Wilkinson ◽  
Stephen Watt ◽  
Christopher J. Penkett ◽  
W. Mark Toone ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Hydrogen Peroxide ◽  
Oxidative Damage ◽  
Stress Responses ◽  
Zinc Finger Protein ◽  
Transcriptional Response ◽  
Minor Role ◽  
Transcriptional Responses ◽  
Regulatory Pathways

Cellular protection against oxidative damage is relevant to ageing and numerous diseases. We analyzed the diversity of genome-wide gene expression programs and their regulation in response to various types and doses of oxidants in Schizosaccharomyces pombe. A small core gene set, regulated by the AP-1–like factor Pap1p and the two-component regulator Prr1p, was universally induced irrespective of oxidant and dose. Strong oxidative stresses led to a much larger transcriptional response. The mitogen-activated protein kinase (MAPK) Sty1p and the bZIP factor Atf1p were critical for the response to hydrogen peroxide. A newly identified zinc-finger protein, Hsr1p, is uniquely regulated by all three major regulatory systems (Sty1p-Atf1p, Pap1p, and Prr1p) and in turn globally supports gene expression in response to hydrogen peroxide. Although the overall transcriptional responses to hydrogen peroxide and t-butylhydroperoxide were similar, to our surprise, Sty1p and Atf1p were less critical for the response to the latter. Instead, another MAPK, Pmk1p, was involved in surviving this stress, although Pmk1p played only a minor role in regulating the transcriptional response. These data reveal a considerable plasticity and differential control of regulatory pathways in distinct oxidative stress conditions, providing both specificity and backup for protection from oxidative damage.

The Role of PARP-1 in Host-Pathogen Interaction and Cellular Stress Responses

2015 ◽  
Vol 25 (2) ◽  
pp. 175-190 ◽  
Author(s):  
Hui Li ◽  
Qiming Li ◽  
Wu Li ◽  
Longxiang Xie ◽  
Mingliang Zhou ◽  
...  
Keyword(s):  
Stress Responses ◽  
Cellular Stress ◽  
Host Pathogen Interaction ◽  
Host Pathogen ◽  
Cellular Stress Responses ◽  
Parp 1

scholarly journals SIRT7-dependent deacetylation of NPM promotes p53 stabilization following UV-induced genotoxic stress

2021 ◽  
Vol 118 (5) ◽  
pp. e2015339118
Author(s):  
Alessandro Ianni ◽  
Poonam Kumari ◽  
Shahriar Tarighi ◽  
Nicolas G. Simonet ◽  
Daniela Popescu ◽  
...  
Keyword(s):  
Uv Irradiation ◽  
Stress Responses ◽  
Decisive Role ◽  
Genotoxic Stress ◽  
Cellular Functions ◽  
Intrinsic Cues ◽  
Cellular Stress Responses ◽  
Stress Dependent

Adaptation to different forms of environmental stress is crucial for maintaining essential cellular functions and survival. The nucleolus plays a decisive role as a signaling hub for coordinating cellular responses to various extrinsic and intrinsic cues. p53 levels are normally kept low in unstressed cells, mainly due to E3 ubiquitin ligase MDM2-mediated degradation. Under stress, nucleophosmin (NPM) relocates from the nucleolus to the nucleoplasm and binds MDM2, thereby preventing degradation of p53 and allowing cell-cycle arrest and DNA repair. Here, we demonstrate that the mammalian sirtuin SIRT7 is an essential component for the regulation of p53 stability during stress responses induced by ultraviolet (UV) irradiation. The catalytic activity of SIRT7 is substantially increased upon UV irradiation through ataxia telangiectasia mutated and Rad3 related (ATR)-mediated phosphorylation, which promotes efficient deacetylation of the SIRT7 target NPM. Deacetylation is required for stress-dependent relocation of NPM into the nucleoplasm and MDM2 binding, thereby preventing ubiquitination and degradation of p53. In the absence of SIRT7, stress-dependent stabilization of p53 is abrogated, both in vitro and in vivo, impairing cellular stress responses. The study uncovers an essential SIRT7-dependent mechanism for stabilization of the tumor suppressor p53 in response to genotoxic stress.

scholarly journals Nuclear transporter Importin-13 plays a key role in the oxidative stress transcriptional response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
K. A. Gajewska ◽  
H. Lescesen ◽  
M. Ramialison ◽  
K. M. Wagstaff ◽  
D. A. Jans
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Transcription Factors ◽  
Embryonic Stem Cells ◽  
Stress Responses ◽  
Nuclear Export ◽  
De Novo ◽  
Embryonic Stem ◽  
Wild Type ◽  
Stress Dependent

AbstractThe importin superfamily member Importin-13 is a bidirectional nuclear transporter. To delineate its functional roles, we performed transcriptomic analysis on wild-type and Importin-13-knockout mouse embryonic stem cells, revealing enrichment of differentially expressed genes involved in stress responses and apoptosis regulation. De novo promoter motif analysis on 277 Importin-13-dependent genes responsive to oxidative stress revealed an enrichment of motifs aligned to consensus sites for the transcription factors specificity protein 1, SP1, or Kruppel like factor 4, KLF4. Analysis of embryonic stem cells subjected to oxidative stress revealed that Importin-13-knockout cells were more resistant, with knockdown of SP1 or KLF4 helping protect wild-type embryonic stem cells against stress-induced death. Importin-13 was revealed to bind to SP1 and KLF4 in a cellular context, with a key role in oxidative stress-dependent nuclear export of both transcription factors. The results are integral to understanding stress biology, highlighting the importance of Importin-13 in the stress response.

scholarly journals Carnosol promotes endothelial differentiation under H2O2-induced oxidative stress

2017 ◽  
Vol 69 (2) ◽  
pp. 299-304
Author(s):  
Shulin Ou ◽  
Jianfeng Lv ◽  
Liming Peng ◽  
Jin Zhao ◽  
Luxiang Chi
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Antioxidant Defense ◽  
Caspase 3 ◽  
Defense Mechanism ◽  
Stem Cell Marker ◽  
Endothelial Differentiation ◽  
H2o2 Treatment ◽  
Endothelial Cell Differentiation ◽  
Antiinflammatory Compound

Oxidative stress causes deregulation of endothelial cell differentiation. Carnosol is a potent antioxidant and antiinflammatory compound. In the present study, we examined whether the antioxidant effect of carnosol might protect bone marrow stem cells against H2O2-induced oxidative stress and promote endothelial differentiation. We examined cell viability by the MTT assay; oxidative stress and apoptosis were analyzed through changes in ROS levels, apoptotic ratio and caspase-3 activity; changes in protein expression of OCT-4, Flk-1, CD31 and Nrf-2 were assessed by Western blot analysis. H2O2 treatment increased oxidative stress and reduced cell viability, while the stem cell marker OCT-4 and endothelial markers Flk-1, CD31 were significantly downregulated as a result of the treatment with H2O2. Treatment with carnosol improved the antioxidant status, increased OCT-4 expression and promoted endothelial differentiation. This study provides evidence that carnosol could increase the antioxidant defense mechanism and promote endothelial differentiation.

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