Bovine embryo survival under oxidative-stress conditions is associated with activity of the NRF2-mediated oxidative-stress-response pathway

2014 ◽  
Vol 81 (6) ◽  
pp. 497-513 ◽  
Author(s):  
Ahmed Amin ◽  
Ahmed Gad ◽  
Dessie Salilew-Wondim ◽  
Sigit Prastowo ◽  
Eva Held ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Stress Conditions ◽  
Bovine Embryo ◽  
Embryo Survival ◽  
Stress Response Pathway

scholarly journals Stringent Response Governs the Virulence and Oxidative Stress Resistance of Francisella tularensis

2019 ◽  
Author(s):  
Zhuo Ma ◽  
Kayla King ◽  
Maha Alqahtani ◽  
Madeline Worden ◽  
Parthasarthy Muthuraman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Francisella Tularensis ◽  
Stress Resistance ◽  
Stringent Response ◽  
Oxidative Stress Response ◽  
Stress Conditions ◽  
Gram Negative ◽  
And Oxidative Stress ◽  
Starvation Conditions

AbstractFrancisella tularensis is a Gram-negative bacterium responsible for causing tularemia in the northern hemisphere. F. tularensis has long been developed as a biological weapon due to its ability to cause severe illness upon inhalation of as few as ten organisms and based on its potential to be used as a bioterror agent is now classified as a Tier 1 Category A select agent by the CDC. The stringent response facilitates bacterial survival under nutritionally challenging starvation conditions. The hallmark of stringent response is the accumulation of the effector molecules ppGpp and (p)ppGpp known as stress alarmones. The relA and spoT gene products generate alarmones in several Gram-negative bacterial pathogens. RelA is a ribosome-associated ppGpp synthetase that gets activated under amino acid starvation conditions whereas, SpoT is a bifunctional enzyme with both ppGpp synthetase and ppGpp hydrolase activities. Francisella encodes a monofunctional RelA and a bifunctional SpoT enzyme. Previous studies have demonstrated that stringent response under nutritional stresses increases expression of virulence-associated genes encoded on Francisella Pathogenicity Island. This study investigated how stringent response governs the oxidative stress response of F. tularensis. We demonstrate that RelA/SpoT-mediated ppGpp production alters global gene transcriptional profile of F. tularensis in the presence of oxidative stress. The lack of stringent response in relA/spoT gene deletion mutants of F. tularensis makes bacteria more susceptible to oxidants, attenuates survival in macrophages, and virulence in mice. Mechanistically, we provide evidence that the stringent response in Francisella contributes to oxidative stress resistance by enhancing the production of antioxidant enzymes.ImportanceThe unique intracellular life cycle of Francisella in addition to nutritional stress also exposes the bacteria to oxidative stress conditions upon its brief residence in the phagosomes, and escape into the cytosol where replication takes place. However, the contribution of the stringent response in gene regulation and management of the oxidative stress response when Francisella is experiencing oxidative stress conditions is not known. Our results provide a link between the stringent and oxidative stress responses. This study further improves our understanding of the intracellular survival mechanisms of F. tularensis.

scholarly journals Synergistic Activation of the Nrf2-ARE Oxidative Stress Response Pathway by a Combination of Botanical Extracts

2016 ◽  
Vol 3 (02) ◽  
pp. e27-e30 ◽  
Author(s):  
Stephen Missler ◽  
Arun Rajgopal ◽  
Samantha Roloff ◽  
Jeffrey Scholten ◽  
Charlie Burns ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Synergistic Activation ◽  
Stress Response Pathway ◽  
Botanical Extracts

scholarly journals The Translation Elongation Factor eEF1B Plays a Role in the Oxidative Stress Response Pathway

RNA Biology ◽  
2004 ◽  
Vol 1 (2) ◽  
pp. 89-94 ◽  
Author(s):  
Olubunmi Olarewaju ◽  
Pedro A. Ortiz ◽  
Wasimul Q. Chowdhury ◽  
Ishita Chatterjee ◽  
Terri Goss Kinzy
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Elongation Factor ◽  
Oxidative Stress Response ◽  
Translation Elongation Factor ◽  
Translation Elongation ◽  
Stress Response Pathway

scholarly journals Inducible expression of (pp)pGpp synthetases in Staphylococcus aureus is associated with activation of stress response genes

2020 ◽  
Author(s):  
Petra Horvatek ◽  
Andrew Magdy Fekry Hanna ◽  
Fabio Lino Gratani ◽  
Daniela Keinhörster ◽  
Natalya Korn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Stress Response ◽  
Stringent Response ◽  
Trna Synthetase ◽  
Oxidative Stress Response ◽  
Stress Conditions ◽  
Additional Stress ◽  
Iron Storage ◽  
Transcriptional Induction

AbstractThe stringent response is characterized by the synthesis of the messenger molecules pppGpp, ppGpp or pGpp (here collectively designated (pp)pGpp). The phenotypic consequences resulting from (pp)pGpp accumulation vary among species and can be mediated by different underlying mechanisms. Most genome-wide analyses have been performed under stress conditions, which often mask the immediate effects of (pp)pGpp-mediated regulatory circuits. In Staphylococcus aureus, (pp)pGpp can be synthesized via the RelA-SpoT-homolog (RSHSau) upon amino acid limitation or via one of the two small (pp)pGpp synthetases RelP or RelQ, upon cell wall stress. We used RNA-Seq to compare the global effects in response to transcriptional induction of the synthetase domain of RSH (RSH-Syn), RelP or RelQ without the need to apply additional stress conditions. Enzyme expression resulted in changes in the nucleotide pool similar to induction of the stringent response via the tRNA synthetase inhibitor mupirocin: a reduction in the GTP pool, an increase in the ATP pool and synthesis of pppGpp, ppGpp and pGpp. Induction of all three enzymes resulted in similar changes in the transcriptome. However, RelQ was less active than RSH-Syn and RelP, indicating strong restriction of its (pp)pGpp-synthesis activity in vivo. Genes involved in the SOS response, iron storage (e.g. ftnA, dps), oxidative stress response (e.g., katA, sodA) and the the psmα1-4 and psmß1-2 operons coding for cytotoxic, phenole soluble modulins (PSMs) were highly upregulated upon (pp)pGpp synthesis. Analyses of the ftnA, dps and psm genes in different regulatory mutants revealed that their (pp)pGpp-dependent regulation can occur independent of the regulators PerR, Fur, SarA or CodY. Moreover, psm expression is uncoupled from expression of the quorum sensing system Agr, the main known psm activator. The expression of central genes of the oxidative stress response protects the bacteria from anticipated ROS stress derived from PSMs or exogenous sources. Thus, we identified a new link between the stringent response and oxidative stress in S. aureus that is likely crucial for survival upon phagocytosis.SignificanceMost bacteria make use of the second messenger (pp)pGpp to reprogram bacterial metabolism under nutrient-limiting conditions. In the human pathogen Staphylococcus aureus, (pp)pGpp plays an important role in virulence, phagosomal escape and antibiotic tolerance. Here, we analyzed the immediate consequences of (pp)pGpp synthesis upon transcriptional induction of the (pp)pGpp-producing enzymes RSH, RelP or RelQ. (pp)pGpp synthesis provokes immediate changes in the nucleotide pool and severely impacts the expression of hundreds of genes. A main consequence of (pp)pGpp synthesis in S. aureus is the induction of ROS-inducing toxic phenol-soluble modulins (PSMs) and simultaneous expression of the detoxifying system to protect the producer. This mechanism is likely of special advantage for the pathogen after phagocytosis.

scholarly journals Inducible expression of (pp)pGpp synthetases in Staphylococcus aureus is associated with activation of stress response genes

PLoS Genetics ◽  
2020 ◽  
Vol 16 (12) ◽  
pp. e1009282
Author(s):  
Petra Horvatek ◽  
Andrea Salzer ◽  
Andrew Magdy Fekry Hanna ◽  
Fabio Lino Gratani ◽  
Daniela Keinhörster ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Staphylococcus Aureus ◽  
Stress Response ◽  
Stringent Response ◽  
Trna Synthetase ◽  
Oxidative Stress Response ◽  
Stress Conditions ◽  
Additional Stress ◽  
Iron Storage

The stringent response is characterized by the synthesis of the messenger molecules pppGpp, ppGpp or pGpp (here collectively designated (pp)pGpp). The phenotypic consequences resulting from (pp)pGpp accumulation vary among species and can be mediated by different underlying mechanisms. Most genome-wide analyses have been performed under stress conditions, which often mask the immediate effects of (pp)pGpp-mediated regulatory circuits. In Staphylococcus aureus, (pp)pGpp can be synthesized via the RelA-SpoT-homolog, RelSau upon amino acid limitation or via one of the two small (pp)pGpp synthetases RelP or RelQ upon cell wall stress. We used RNA-Seq to compare the global effects in response to induction of the synthetase of rel-Syn (coding for the enzymatic region of RelSau) or relQ without the need to apply additional stress conditions. Induction of rel-Syn resulted in changes in the nucleotide pool similar to induction of the stringent response via the tRNA synthetase inhibitor mupirocin: a reduction in the GTP pool, an increase in the ATP pool and synthesis of pppGpp, ppGpp and pGpp. Induction of all three enzymes resulted in similar changes in the transcriptome. However, RelQ was less active than Rel-Syn and RelP, indicating strong restriction of its (pp)pGpp-synthesis activity in vivo. (pp)pGpp induction resulted in the downregulation of many genes involved in protein and RNA/DNA metabolism. Many of the (pp)pGpp up-regulated genes are part of the GTP sensitive CodY regulon and thus likely regulated through lowering of the GTP pool. New CodY independent transcriptional changes were detected including genes involved in the SOS response, iron storage (e.g. ftnA, dps), oxidative stress response (e.g., perR katA, sodA) and the psmα1–4 and psmß1-2 operons coding for cytotoxic, phenol soluble modulins (PSMs). Analyses of the ftnA, dps and psm genes in different regulatory mutants revealed that their (pp)pGpp-dependent regulation can occur independent of the regulators PerR, Fur, SarA or CodY. Moreover, psm expression is uncoupled from expression of the quorum sensing system Agr, the main known psm activator. The expression of central genes of the oxidative stress response protects the bacteria from anticipated ROS stress derived from PSMs or exogenous sources. Thus, we identified a new link between the stringent response and oxidative stress in S. aureus that is likely crucial for survival upon phagocytosis.

scholarly journals A Combination of Genomic Approaches Reveals the Role of FOXO1a in Regulating an Oxidative Stress Response Pathway

PLoS ONE ◽  
2008 ◽  
Vol 3 (2) ◽  
pp. e1670 ◽  
Author(s):  
Paola de Candia ◽  
Ran Blekhman ◽  
Adrien E. Chabot ◽  
Alicia Oshlack ◽  
Yoav Gilad
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Oxidative Stress Response ◽  
Stress Response Pathway

118 EXOSOME-MEDIATED OXIDATIVE STRESS RESPONSE IN BOVINE GRANULOSA CELLS

2017 ◽  
Vol 29 (1) ◽  
pp. 167
Author(s):  
M. Saeed-Zidane ◽  
D. Salilew-Wondim ◽  
L. Linden ◽  
E. Held ◽  
C. Neuhoff ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Stress Response ◽  
Granulosa Cells ◽  
Culture Medium ◽  
Oxidative Stress Response ◽  
Stress Conditions ◽  
Oxygen Species ◽  
Mitochondrial Distribution

Exosomes are nano-sized (30–100 nm) extracellular membrane vesicles released through exocytosis process in most cells and biological fluids. They contain a cargo of nucleic acids, proteins, lipids and play a vital role in cell-cell communications. Various cell types have been shown to release exosomes into extracellular space as a response to various environmental stress conditions. However, little is known about the response of granulosa cells to oxidative stress, with regard to release of exosomes that may carry mRNA and protein molecules related to cellular oxidative stress response. Here we aimed to investigate the potential release of stress elements by granulosa cells to culture media through exosomes under oxidative stress conditions. For that, bovine granulosa cells from small follicles were aspirated and cultured in DMEM/F-12 media supplemented with exosome free fetal bovine serum (Exo-FBS) and treated with 5 µM H2O2 for 40 min. Granulosa cells were collected 24 h post-treatment to quantify the expression of antioxidants (Nrf2, Keap1, SOD1, CAT1, PRDX1, HOMOX1, TXN1, and NQO1), cell proliferation (PCNA and CNND2), cell differentiation (CYP11A1 and STAR), apoptosis (Casp3), and antiapoptosis (BCL2L1) genes. Reactive oxygen species accumulation, mitochondrial distribution, cell viability, and cell cycle assays were performed in cultured granulosa cells, and the culture medium was used to isolate exosomes using ultracentrifugation procedure. The identity of exosomes was confirmed by immunoblotting of Alix and CD63 proteins, and the expression level of antioxidant was analysed in mRNA isolated from exosomes. Data from 3 independent biological replicates were statistically analysed using the 2-tailed t-test. Results showed that H2O2 treatment increased mRNA and protein level of antioxidants (Nrf2, PRDX1, and TXN1), as well as cell differentiation and apoptosis-related genes compared to untreated controls. However, granulosa cells treated with H2O2 showed lower expression of cell proliferation marker genes (PCNA and CNND2). Cells treated with H2O2 showed increases in reactive oxygen species level, inadequate mitochondrial distribution, and lower cell viability. Cell cycle assay revealed a reduction in G0/G1 proportion and increase in G2 phase in cells treated with H2O2. Higher levels of antioxidant (Nrf2, CAT1, and TXN1) transcripts were detected in exosomes isolated from media with cells under oxidative stress conditions compared to the controls. Labelling and co-transfection of exosomes from stressed cell culture medium with untreated treated recipient granulosa cells resulted in increased abundance of cellular mRNA and protein of Nrf2 and CAT1 in those cells. In conclusion, granulosa cells exposed to oxidative stress could release exosomes that carry molecules related to oxidative stress response, which can be up taken by recipient cells.

scholarly journals Chronic Variable Stress Is Responsible for Lipid and DNA Oxidative Disorders and Activation of Oxidative Stress Response Genes in the Brain of Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Mariola Herbet ◽  
Agnieszka Korga ◽  
Monika Gawrońska-Grzywacz ◽  
Magdalena Izdebska ◽  
Iwona Piątkowska-Chmiel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Indirect Evidence ◽  
Oxidative Stress Response ◽  
Stress Conditions ◽  
Ros Generation ◽  
Repair System ◽  
Stress Response Genes ◽  
Chronic Variable Stress ◽  
The Brain

Chronic environmental stress is associated with reactive oxygen species (ROS) overproduction and the pathogenesis of depression. The purpose of this study was to evaluate biochemical and molecular changes associated with ROS generation in the brains of rats submitted to chronic variable stress. Male Wistar rats (50–55 days old, weighing 200–250 g) were divided in two groups (n=10): control and stressed. Rats in the stressed group were exposed to stress conditions for 40 days. The animals were decapitated and the brain samples were collected. In prefrontal cortex, we measured the following biochemical parameters: lipid peroxidation and concentration of glutathione—GSH, GSSG, GSH/GSSG ratio, glutathione peroxidase, and glutathione reductase activities. In the hippocampus marker of DNA, oxidative damage and expression of DNA-repairing genes (Ogg1,MsrA) and gene-encoding antioxidative transcriptional factor (Nrf2) were determined. The results demonstrate indirect evidence of ROS overproduction and presence of oxidative stress. They also reveal disruption of oxidative defense systems (decreased GR activity, diminished GSH/GSSG ratio, and decreasedNrf2expression) and activation of the oxidative DNA repair system (increasedOgg1andMsrAexpression). Together, the presented data suggest that independent activation of oxidative stress response genes occurs in chronic variable stress conditions.

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