Lamin B1 controls oxidative stress responses via Oct-1

Interaction of lamins with chromatin and transcription factors regulate transcription. Oct-1 has previously been shown to colocalize partly with B-type lamins and is essential for transcriptional regulation of oxidative stress response genes. Using sequential extraction, co-immunoprecipitation (IP), fluorescence loss in photobleaching, and fluorescence resonance energy transfer, we confirm Oct-1–lamin B1 association at the nuclear periphery and show that this association is lost in Lmnb1Δ/Δ cells. We show that several Oct-1–dependent genes, including a subset involved in oxidative stress response, are dysregulated in Lmnb1Δ/Δ cells. Electrophoretic mobility shift assay and chromatin IP reveal that Oct-1 binds to the putative octamer-binding sequences of the dysregulated genes and that this activity is increased in cells lacking functional lamin B1. Like Oct1−/− cells, Lmnb1Δ/Δ cells have elevated levels of reactive oxygen species and are more susceptible to oxidative stress. Sequestration of Oct-1 at the nuclear periphery by lamin B1 may be a mechanism by which the nuclear envelope can regulate gene expression and contribute to the cellular response to stress, development, and aging.

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Environmental Conditions Modulate the Transcriptomic Response of Both Caulobacter crescentus Morphotypes to Cu Stress

Microorganisms ◽

10.3390/microorganisms9061116 ◽

2021 ◽

Vol 9 (6) ◽

pp. 1116

Author(s):

Laurens Maertens ◽

Pauline Cherry ◽

Françoise Tilquin ◽

Rob Van Houdt ◽

Jean-Yves Matroule

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Stress Responses ◽

Caulobacter Crescentus ◽

Oxidative Stress Response ◽

Transport Systems ◽

Transcriptomic Response ◽

Swarmer Cell ◽

Cu Stress ◽

Cellular Environment

Bacteria encounter elevated copper (Cu) concentrations in multiple environments, varying from mining wastes to antimicrobial applications of copper. As the role of the environment in the bacterial response to Cu ion exposure remains elusive, we used a tagRNA-seq approach to elucidate the disparate responses of two morphotypes of Caulobacter crescentus NA1000 to moderate Cu stress in a complex rich (PYE) medium and a defined poor (M2G) medium. The transcriptome was more responsive in M2G, where we observed an extensive oxidative stress response and reconfiguration of the proteome, as well as the induction of metal resistance clusters. In PYE, little evidence was found for an oxidative stress response, but several transport systems were differentially expressed, and an increased need for histidine was apparent. These results show that the Cu stress response is strongly dependent on the cellular environment. In addition, induction of the extracytoplasmic function sigma factor SigF and its regulon was shared by the Cu stress responses in both media, and its central role was confirmed by the phenotypic screening of a sigF::Tn5 mutant. In both media, stalked cells were more responsive to Cu stress than swarmer cells, and a stronger basal expression of several cell protection systems was noted, indicating that the swarmer cell is inherently more Cu resistant. Our approach also allowed for detecting several new transcription start sites, putatively indicating small regulatory RNAs, and additional levels of Cu-responsive regulation.

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Clade III cytokinin response factors share common roles in response to oxidative stress responses linked to cytokinin synthesis

Journal of Experimental Botany ◽

10.1093/jxb/erab076 ◽

2021 ◽

Vol 72 (8) ◽

pp. 3294-3306

Author(s):

Ariel M Hughes ◽

H Tucker Hallmark ◽

Lenka Plačková ◽

Ondrej Novák ◽

Aaron M Rashotte

Keyword(s):

Oxidative Stress ◽

Transcription Factors ◽

Stress Response ◽

Stress Responses ◽

Oxidative Stress Response ◽

Response Factors ◽

Ontology Term ◽

Regulated Expression ◽

Cytokinin Response ◽

Oxidative Stress Responses

Abstract Cytokinin response factors (CRFs) are transcription factors that are involved in cytokinin (CK) response, as well as being linked to abiotic stress tolerance. In particular, oxidative stress responses are activated by Clade III CRF members, such as AtCRF6. Here we explored the relationships between Clade III CRFs and oxidative stress. Transcriptomic responses to oxidative stress were determined in two Clade III transcription factors, Arabidopsis AtCRF5 and tomato SlCRF5. AtCRF5 was required for regulated expression of >240 genes that are involved in oxidative stress response. Similarly, SlCRF5 was involved in the regulated expression of nearly 420 oxidative stress response genes. Similarities in gene regulation by these Clade III members in response to oxidative stress were observed between Arabidopsis and tomato, as indicated by Gene Ontology term enrichment. CK levels were also changed in response to oxidative stress in both species. These changes were regulated by Clade III CRFs. Taken together, these findings suggest that Clade III CRFs play a role in oxidative stress response as well as having roles in CK signaling.

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TrmB, a tRNA m7G46 methyltransferase, plays a role in hydrogen peroxide resistance and positively modulates the translation of katA and katB mRNAs in Pseudomonas aeruginosa

Nucleic Acids Research ◽

10.1093/nar/gkz702 ◽

2019 ◽

Vol 47 (17) ◽

pp. 9271-9281 ◽

Cited By ~ 5

Author(s):

Narumon Thongdee ◽

Juthamas Jaroensuk ◽

Sopapan Atichartpongkul ◽

Jurairat Chittrakanwong ◽

Kamonchanok Chooyoung ◽

...

Keyword(s):

Oxidative Stress ◽

Pseudomonas Aeruginosa ◽

Stress Response ◽

Translational Regulation ◽

Cellular Response ◽

Oxidative Stress Response ◽

Translation Efficiency ◽

Trna Modification ◽

Negative Effect

Abstract Cellular response to oxidative stress is a crucial mechanism that promotes the survival of Pseudomonas aeruginosa during infection. However, the translational regulation of oxidative stress response remains largely unknown. Here, we reveal a tRNA modification-mediated translational response to H2O2 in P. aeruginosa. We demonstrated that the P. aeruginosa trmB gene encodes a tRNA guanine (46)-N7-methyltransferase that catalyzes the formation of m7G46 in the tRNA variable loop. Twenty-three tRNA substrates of TrmB with a guanosine residue at position 46 were identified, including 11 novel tRNA substrates. We showed that loss of trmB had a strong negative effect on the translation of Phe- and Asp-enriched mRNAs. The trmB-mediated m7G modification modulated the expression of the catalase genes katA and katB, which are enriched with Phe/Asp codons at the translational level. In response to H2O2 exposure, the level of m7G modification increased, consistent with the increased translation efficiency of Phe- and Asp-enriched mRNAs. Inactivation of trmB led to decreased KatA and KatB protein abundance and decreased catalase activity, resulting in H2O2-sensitive phenotype. Taken together, our observations reveal a novel role of m7G46 tRNA modification in oxidative stress response through translational regulation of Phe- and Asp-enriched genes, such as katA and katB.

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Antagonistic effects of chemical mixtures on the oxidative stress response are silenced by heat stress and reversed under dietary restriction

Exposome ◽

10.1093/exposome/osab005 ◽

2021 ◽

Author(s):

Karthik Suresh Arulalan ◽

Javier Huayta ◽

Jonathan W Stallrich ◽

Adriana San-Miguel

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Design Of Experiments ◽

Stress Responses ◽

Current Knowledge ◽

Oxidative Stress Response ◽

Chemical Mixtures ◽

C Elegans ◽

Chemical Agents ◽

Limited Food

Abstract Chemical agents released into the environment can induce oxidative stress in organisms, which is detrimental for health. Although environmental exposures typically include multiple chemicals, organismal studies on oxidative stress derived from chemical agents commonly study exposures to individual compounds. In this work, we explore how chemical mixtures drive the oxidative stress response under various conditions in the nematode C. elegans, by quantitatively assessing levels of gst-4 expression. Our results indicate that naphthoquinone mixtures drive responses differently than individual components, and that altering environmental conditions, such as increased heat and reduced food availability, result in dramatically different oxidative stress responses mounted by C. elegans. When exposed to heat, the oxidative stress response is diminished. Notably, when exposed to limited food, the oxidative stress response specific to juglone is significantly heightened, while identified antagonistic interactions between some naphthoquinone components in mixtures are abolished. This implies that organismal responses to xenobiotics is confounded by environment and stressor interactions. Given the high number of variables under study, and their potential combinations, a simplex centroid design was used to capture such non-trivial response over the design space. This makes the case for the adoption of Design of Experiments approaches as they can greatly expand the experimental space probed in noisy biological readouts, and in combinatorial experiments. Our results also reveal gaps in our current knowledge of the organismal oxidative stress response, which can be addressed by employing sophisticated design of experiments approaches to identify significant interactions.

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Identification of ubiquitin Ser57 kinases regulating the oxidative stress response in yeast

10.1101/2020.06.20.162883 ◽

2020 ◽

Author(s):

Nathaniel L. Hepowit ◽

Kevin N. Pereira ◽

Jessica M. Tumolo ◽

Walter J. Chazin ◽

Jason A. MacGurn

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Membrane Trafficking ◽

Stress Responses ◽

Protein Quality ◽

Oxidative Stress Response ◽

Post Translational Modifications ◽

Cellular Processes ◽

Proteotoxic Stress ◽

Substrate Proteins

ABSTRACTUbiquitination regulates many different cellular processes, including protein quality control, membrane trafficking, and stress responses. The diversity of ubiquitin functions in the cell is partly due to its ability to form chains with distinct linkages that can alter the fate of substrate proteins in unique ways. The complexity of the ubiquitin code is further enhanced by post-translational modifications on ubiquitin itself, the biological functions of which are not well understood. Here, we present genetic and biochemical evidence that serine 57 (Ser57) phosphorylation of ubiquitin functions in stress responses in Saccharomyces cerevisiae, including the oxidative stress response. We also identify and characterize the first known Ser57 ubiquitin kinases in yeast and human cells, and we report that two Ser57 ubiquitin kinases regulate the oxidative stress response in yeast. These studies implicate ubiquitin phosphorylation at the Ser57 position as an important modifier of ubiquitin function, particularly in response to proteotoxic stress.

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Translational Regulation Promotes Oxidative Stress Resistance in the Human Fungal Pathogen Cryptococcus neoformans

10.1101/735225 ◽

2019 ◽

Author(s):

Jay Leipheimer ◽

Amanda L. M. Bloom ◽

Christopher S. Campomizzi ◽

Yana Salei ◽

John C. Panepinto

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Cryptococcus Neoformans ◽

Stress Responses ◽

Carbon Starvation ◽

Oxidative Stress Response ◽

Initiation Factor ◽

Mammalian Host ◽

Cellular Stresses ◽

Translational Suppression

AbstractCryptococcus neoformans is one of the few environmental fungi that can survive within a mammalian host and cause disease. Although many of the factors responsible for establishing virulence have been recognized, how they are expressed in response to certain host derived cellular stresses is rarely addressed. Here we characterize the temporal translational response of C. neoformans to oxidative stress. We find that translation is largely inhibited through the phosphorylation of the critical initiation factor elF2α by a sole kinase. Preventing elF2α mediated translational suppression resulted in growth sensitivity to hydrogen peroxide (H2O2). Our work suggests that translational repression in response to H2O2 partly facilitates oxidative stress adaptation by accelerating the decay of abundant non-stress related transcripts while facilitating the proper expression of critical oxidative stress response factors. Carbon starvation, which seems to induce translational suppression that is independent elF2α, partly restored transcript decay and the expression of the critical oxidative stress response transcript Thioredoxin Reductase 1 (TRR1). Our results illustrate translational suppression as a key determinant of select mRNA decay, gene expression, and subsequent survival in response to oxidative stress.ImportanceFungal survival in a mammalian host requires the coordinated expression and downregulation of a large cohort of genes in response to cellular stresses. Initial infection with C. neoformans occurs at the lungs, where it interacts with host macrophages. Surviving macrophage derived cellular stresses, such as the production of reactive oxygen and nitrogen species, is believed to promote dissemination into the central nervous system. Therefore, investigating how an oxidative stress resistant phenotype is brought about in C. neoformans furthers our understanding of not only fungal pathogenesis but also unveils mechanisms of stress induced gene reprogramming. We discovered that H2O2 derived oxidative stress resulted in severe translational suppression and that this suppression was necessary for the accelerated decay and expression of tested transcripts. Surprisingly, compounding oxidative stress with carbon starvation resulted in a decrease in peroxide mediated killing, revealing unexpected synergy between stress responses.

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Proteomic signatures of acute oxidative stress response to paraquat in the mouse heart

10.1101/2020.05.29.124487 ◽

2020 ◽

Author(s):

Vishantie Dostal ◽

Silas D. Wood ◽

Cody T. Thomas ◽

Yu Han ◽

Edward Lau ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Protein Expression ◽

Stress Responses ◽

Oxidative Stress Response ◽

Cardiac Response ◽

Differential Sensitivity ◽

Mouse Heart ◽

Rapid Reduction ◽

Proteome Changes

AbstractThe heart is sensitive to oxidative damage but a global view on how the cardiac proteome responds to oxidative stressors has yet to fully emerge. Using quantitative tandem mass spectrometry, we assessed the effects of acute exposure of the oxidative stress inducer paraquat on protein expression in mouse hearts. We observed widespread protein expression changes in the paraquat-exposed heart especially in organelle-containing subcellular fractions. During cardiac response to acute oxidative stress, proteome changes are consistent with a rapid reduction of mitochondrial metabolism, coupled with activation of multiple antioxidant proteins, reduction of protein synthesis and remediation of proteostasis. In addition to differential expression, we saw evidence of spatial reorganizations of the cardiac proteome including the translocation of hexokinase 2 to more soluble fractions. Treatment with the antioxidants Tempol and MitoTEMPO reversed many proteomic signatures of paraquat but this reversal was incomplete. We also identified a number of proteins with unknown function in the heart to be triggered by paraquat, suggesting they may have functions in oxidative stress response. Surprisingly, protein expression changes in the heart correlate poorly with those in the lung, consistent with differential sensitivity or stress response in these two organs. The results provide insights into oxidative stress responses in the heart and may avail the search for new therapeutic targets.

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Oxidative Stress Response and Characterization of theoxyR-ahpC and furA-katG Loci inMycobacterium marinum

Journal of Bacteriology ◽

10.1128/jb.180.18.4856-4864.1998 ◽

1998 ◽

Vol 180 (18) ◽

pp. 4856-4864 ◽

Cited By ~ 64

Author(s):

E. Pagán-Ramos ◽

J. Song ◽

M. McFalone ◽

M. H. Mudd ◽

V. Deretic

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Promoter Region ◽

Oxidative Stress Response ◽

Mycobacterial Species ◽

Host Pathogen Interactions ◽

Recognition Sequence ◽

Mobility Shift ◽

Host Pathogen

ABSTRACT Oxidative stress response in pathogenic mycobacteria is believed to be of significance for host-pathogen interactions at various stages of infection. It also plays a role in determining the intrinsic susceptibility to isoniazid in mycobacterial species. In this work, we characterized the oxyR-ahpC and furA-katG loci in the nontuberculous pathogen Mycobacterium marinum. In contrast to Mycobacterium smegmatis and likeMycobacterium tuberculosis and Mycobacterium leprae, M. marinum was shown to possess a closely linked and divergently oriented equivalents of the regulator of peroxide stress response oxyR and its subordinate geneahpC, encoding a homolog of alkyl hydroperoxide reductase. Purified mycobacterial OxyR was found to bind to theoxyR-ahpC promoter region from M. marinum and additional mycobacterial species. Mobility shift DNA binding analyses using OxyR binding sites from several mycobacteria and a panel of in vitro-generated mutants validated the proposed consensus mycobacterial recognition sequence. M. marinum AhpC levels detected by immunoblotting, were increased upon treatment with H2O2, in keeping with the presence of a functional OxyR and its binding site within the promoter region ofahpC. In contrast, OxyR did not bind to the sequences upstream of the katG structural gene, and katGexpression did not follow the pattern seen with ahpC. Instead, a new open reading frame encoding a homolog of the ferric uptake regulator Fur was identified immediately upstream ofkatG in M. marinum. The furA-katGlinkage and arrangement are ubiquitous in mycobacteria, suggesting the presence of additional regulators of oxidative stress response and potentially explaining the observed differences in ahpC andkatG expression. Collectively, these findings broaden our understanding of oxidative stress response in mycobacteria. They also suggest that M. marinum will be useful as a model system for studying the role of oxidative stress response in mycobacterial physiology, intracellular survival, and other host-pathogen interactions associated with mycobacterial diseases.

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Nrf2, the Major Regulator of the Cellular Oxidative Stress Response, is Partially Disordered

International Journal of Molecular Sciences ◽

10.3390/ijms22147434 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7434

Author(s):

Nadun C. Karunatilleke ◽

Courtney S. Fast ◽

Vy Ngo ◽

Anne Brickenden ◽

Martin L. Duennwald ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Response ◽

Cellular Response ◽

Rational Design ◽

Oxidative Stress Response ◽

Full Length ◽

Related Factor ◽

Creb Binding Protein ◽

Physiological Importance ◽

Kelch Domain

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription regulator that plays a pivotal role in coordinating the cellular response to oxidative stress. Through interactions with other proteins, such as Kelch-like ECH-associated protein 1 (Keap1), CREB-binding protein (CBP), and retinoid X receptor alpha (RXRα), Nrf2 mediates the transcription of cytoprotective genes critical for removing toxicants and preventing DNA damage, thereby playing a significant role in chemoprevention. Dysregulation of Nrf2 is linked to tumorigenesis and chemoresistance, making Nrf2 a promising target for anticancer therapeutics. However, despite the physiological importance of Nrf2, the molecular details of this protein and its interactions with most of its targets remain unknown, hindering the rational design of Nrf2-targeted therapeutics. With this in mind, we used a combined bioinformatics and experimental approach to characterize the structure of full-length Nrf2 and its interaction with Keap1. Our results show that Nrf2 is partially disordered, with transiently structured elements in its Neh2, Neh7, and Neh1 domains. Moreover, interaction with the Kelch domain of Keap1 leads to protection of the binding motifs in the Neh2 domain of Nrf2, while the rest of the protein remains highly dynamic. This work represents the first detailed structural characterization of full-length Nrf2 and provides valuable insights into the molecular basis of Nrf2 activity modulation in oxidative stress response.

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Regulation by FurC in Anabaena Links the Oxidative Stress Response to Photosynthetic Metabolism

Plant and Cell Physiology ◽

10.1093/pcp/pcz094 ◽

2019 ◽

Vol 60 (8) ◽

pp. 1778-1789 ◽

Cited By ~ 2

Author(s):

Emma Sevilla ◽

Cristina Sarasa-Buisan ◽

Andrï¿½s Gonzï¿½lez ◽

Rafael Cases ◽

Galyna Kufryk ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Division ◽

Stress Response ◽

Essential Gene ◽

D1 Protein ◽

Oxidative Stress Response ◽

O2 Evolution ◽

Mobility Shift ◽

Anabaena Sp ◽

Pcc 7120

Abstract The FUR (Ferric Uptake Regulator) family in Anabaena sp. PCC 7120 consists of three paralogs named FurA (Fur), FurB (Zur) and FurC (PerR). furC seems to be an essential gene in the filamentous nitrogen-fixing strain Anabaena sp. PCC 7120, suggesting that it plays a fundamental role in this organism. In order to better understand the functions of FurC in Anabaena, the phenotype of a derivative strain that overexpresses this regulator (EB2770FurC) has been characterized. The furC-overexpressing variant presented alterations in growth rate, morphology and ultrastructure, as well as higher sensitivity to peroxide than Anabaena sp. PCC 7120. Interestingly, the overexpression of furC led to reduced photosynthetic O2 evolution, increased respiratory activity, and had a significant influence in the composition and efficiency of both photosystems. Comparative transcriptional analyses, together with electrophoretic mobility shift assays allowed the identification of different genes directly controlled by FurC, and involved in processes not previously related to PerR proteins, such as the cell division gene ftsZ and the major thylakoid membrane protease ftsH. The rise in the transcription of ftsH in EB2770FurC cells correlated with reduced levels of the D1 protein, which is involved in the PSII repair cycle. Deregulation of the oxidative stress response in EB2770FurC cells led to the identification of novel FurC targets involved in the response to H2O2 through different mechanisms. These results, together with the effect of furC overexpression on the composition, stability and efficiency of the photosynthetic machinery of Anabaena, disclose novel links between PerR proteins, cell division and photosynthesis in filamentous cyanobacteria.

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