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

2020 ◽  
Vol 10 (1) ◽  
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 ◽  
Data Set

Abstract The 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 and data set here could provide insights into oxidative stress responses in the heart and avail the search for new therapeutic targets.

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

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.

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

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.

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

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.

scholarly journals Tpo1‐mediated spermine and spermidine export controls cell cycle delay and times antioxidant protein expression during the oxidative stress response

EMBO Reports ◽  
2013 ◽  
Vol 14 (12) ◽  
pp. 1113-1119 ◽  
Author(s):  
Antje Krüger ◽  
Jakob Vowinckel ◽  
Michael Mülleder ◽  
Phillip Grote ◽  
Floriana Capuano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Stress Response ◽  
Protein Expression ◽  
Oxidative Stress Response ◽  
Export Controls ◽  
Cell Cycle Delay ◽  
Antioxidant Protein

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

Exposome ◽  
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.

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

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.

scholarly journals Methamphetamine and HIV-Tat Protein Synergistically Induce Oxidative Stress and Blood-Brain Barrier Damage via Transient Receptor Potential Melastatin 2 Channel

2021 ◽  
Vol 12 ◽  
Author(s):  
Jian Huang ◽  
Ruilin Zhang ◽  
Shangwen Wang ◽  
Dongxian Zhang ◽  
Chi-Kwan Leung ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Protein Expression ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Oxidative Stress Response ◽  
Transient Receptor Potential Melastatin ◽  
Trpm2 Channel ◽  
Hiv Tat

Synergistic impairment of the blood-brain barrier (BBB) induced by methamphetamine (METH) and HIV-Tat protein increases the risk of HIV-associated neurocognitive disorders (HAND) in HIV-positive METH abusers. Studies have shown that oxidative stress plays a vital role in METH- and HIV-Tat-induced damage to the BBB but have not clarified the mechanism. This study uses the human brain microvascular endothelial cell line hCMEC/D3 and tree shrews to investigate whether the transient receptor potential melastatin 2 (TRPM2) channel, a cellular effector of the oxidative stress, might regulate synergistic damage to the BBB caused by METH and HIV-Tat. We showed that METH and HIV-Tat damaged the BBB in vitro, producing abnormal cell morphology, increased apoptosis, reduced protein expression of the tight junctions (TJ) including Junctional adhesion molecule A (JAMA) and Occludin, and a junctional associated protein Zonula occludens 1 (ZO1), and increased the flux of sodium fluorescein (NaF) across the hCMEC/D3 cells monolayer. METH and HIV-Tat co-induced the oxidative stress response, reducing catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) activity, as well as increased reactive oxygen species (ROS) and malonaldehyde (MDA) level. Pretreatment with n-acetylcysteine amide (NACA) alleviated the oxidative stress response and BBB damage characterized by improving cell morphology, viability, apoptosis levels, TJ protein expression levels, and NaF flux. METH and HIV-Tat co-induced the activation and high protein expression of the TRPM2 channel, however, early intervention using 8-Bromoadenosine-5′-O-diphosphoribose (8-Br-ADPR), an inhibitor of TPRM2 channel, or TRPM2 gene knockdown attenuated the BBB damage. Oxidative stress inhibition reduced the activation and high protein expression of the TRPM2 channel in the in vitro model, which in turn reduced the oxidative stress response. Further, 8-Br-ADPR attenuated the effects of METH and HIV-Tat on the BBB in tree shrews—namely, down-regulated TJ protein expression and increased BBB permeability to Evans blue (EB) and NaF. In summary, the TRPM2 channel can regulate METH- and HIV-Tat-induced oxidative stress and BBB injury, giving the channel potential for developing drug interventions to reduce BBB injury and neuropsychiatric symptoms in HIV-infected METH abusers.

Biological role, protein expression, subcellular localization, and oxidative stress response of paraoxonase 2 in the intestine of humans and rats

2007 ◽  
Vol 293 (6) ◽  
pp. G1252-G1261 ◽  
Author(s):  
Emile Levy ◽  
Karine Trudel ◽  
Moise Bendayan ◽  
Ernest Seidman ◽  
Edgard Delvin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Stress Response ◽  
Subcellular Localization ◽  
Protein Expression ◽  
Oxidative Stress Response ◽  
Butylated Hydroxytoluene ◽  
Cell Fractionation ◽  
Rat Intestine ◽  
And Oxidative Stress

Oxidative stress is a cardinal manifestation of various intestinal disorders. However, very little knowledge is available on the intestine's inherent defense mechanisms against free radicals. This study was designed to determine the protein expression, subcellular localization and oxidative stress response of paraoxonase 2 (PON2), a member of a powerful antioxidant family in human and rat intestine. Biochemical and ultrastructural experiments all showed a substantial expression of PON2 in human and rat intestine. Western blot analysis disclosed higher levels of PON2 in the jejunum than in the duodenum, ileum, and colon. Cell fractionation revealed a predominant PON2 association with microsomes and lysosomes in the human jejunum, which differed from that in rats. PON2 was detected in the intestine as early as week 15 of gestation and was significantly increased by week 20. Iron ascorbate-mediated lipid peroxidation induced a marked decrease in PON2 expression in intestinal specimens coincidental to an abundant rise in malondialdehyde (MDA). On the other hand, preincubation with potent antioxidants, such as butylated hydroxytoluene, Trolox, and N-acetylcysteine, prevented iron-ascorbate-generating PON2 reduction in parallel with MDA suppression. Finally, the preincubation of permeabilized Caco-2 cells with purified PON2 led to a protection against iron-ascorbate-induced lipid peroxidation. These observations demonstrate that the human intestine is preferentially endowed with a marked PON2 expression compared with the rat intestine and this expression shows a developmental and intracellular pattern of distribution. Furthermore, our observations suggest PON2 protective effects against prooxidant stimuli in the small intestine.

scholarly journals Lamin B1 controls oxidative stress responses via Oct-1

2009 ◽  
Vol 184 (1) ◽  
pp. 45-55 ◽  
Author(s):  
Ashraf N. Malhas ◽  
Chiu Fan Lee ◽  
David J. Vaux
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Stress Responses ◽  
Cellular Response ◽  
Nuclear Periphery ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Oxidative Stress Response ◽  
Mobility Shift ◽  
Lamin B1

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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