scholarly journals A molecular switch for Cdc48 activity and localization during oxidative stress and aging

2019 ◽  
Author(s):  
Meytal Radzinski ◽  
Ohad Yogev ◽  
Yarden Yesharim ◽  
Esther S. Brielle ◽  
Ran Israeli ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Degradation ◽  
Polypeptide Chain ◽  
Thiol Group ◽  
Oxidative Stress Response ◽  
Mitochondrial Fragmentation ◽  
Chronological Aging ◽  
Sensitive Site ◽  
Redox Switch ◽  
Cellular Oxidation

SummaryControl over a healthy proteome begins with the birth of the polypeptide chain and ends with coordinated protein degradation. One of the major players in eukaryotic protein degradation is the essential and highly conserved ATPase, Cdc48 (p97/VCP in mammals). Cdc48 mediates clearance of misfolded proteins from the nucleus, cytosol, ER, mitochondria, and more. Here we dissect the crosstalk between cellular oxidation and Cdc48 activity by identification of a redox-sensitive site, Cys115. By integrating proteomics, biochemistry, microscopy, and bioinformatics, we show that removal of Cys115’s redox-sensitive thiol group leads to accumulation of Cdc48 in the nucleus and consequently, results in severe defects in the oxidative stress response, mitochondrial fragmentation, and a decrease in ERAD and sterol biogenesis. We have thus identified a unique redox switch in Cdc48, which may provide a clearer picture of the importance of Cdc48’s localization in maintaining a “healthy” proteome during oxidative stress and chronological aging in yeast.

scholarly journals Global redox proteome and phosphoproteome analysis reveals redox switch in Akt

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhiduan Su ◽  
James G. Burchfield ◽  
Pengyi Yang ◽  
Sean J. Humphrey ◽  
Guang Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Redox Regulation ◽  
Binding Pocket ◽  
Pleckstrin Homology Domain ◽  
Global Changes ◽  
Cysteine Oxidation ◽  
Post Translational Modifications ◽  
Mechanistic Analysis ◽  
Redox Switch ◽  
Cellular Oxidation

AbstractProtein oxidation sits at the intersection of multiple signalling pathways, yet the magnitude and extent of crosstalk between oxidation and other post-translational modifications remains unclear. Here, we delineate global changes in adipocyte signalling networks following acute oxidative stress and reveal considerable crosstalk between cysteine oxidation and phosphorylation-based signalling. Oxidation of key regulatory kinases, including Akt, mTOR and AMPK influences the fidelity rather than their absolute activation state, highlighting an unappreciated interplay between these modifications. Mechanistic analysis of the redox regulation of Akt identified two cysteine residues in the pleckstrin homology domain (C60 and C77) to be reversibly oxidized. Oxidation at these sites affected Akt recruitment to the plasma membrane by stabilizing the PIP3 binding pocket. Our data provide insights into the interplay between oxidative stress-derived redox signalling and protein phosphorylation networks and serve as a resource for understanding the contribution of cellular oxidation to a range of diseases.

scholarly journals Protective Role of Glutathione in the Hippocampus after Brain Ischemia

2021 ◽  
Vol 22 (15) ◽  
pp. 7765
Author(s):  
Youichirou Higashi ◽  
Takaaki Aratake ◽  
Takahiro Shimizu ◽  
Shogo Shimizu ◽  
Motoaki Saito
Keyword(s):  
Oxidative Stress ◽  
Neuronal Death ◽  
Excitatory Amino Acid ◽  
Ischemia Reperfusion ◽  
Thiol Group ◽  
Protective Role ◽  
Key Factor ◽  
Rate Limiting ◽  
Cysteine Uptake

Stroke is a major cause of death worldwide, leading to serious disability. Post-ischemic injury, especially in the cerebral ischemia-prone hippocampus, is a serious problem, as it contributes to vascular dementia. Many studies have shown that in the hippocampus, ischemia/reperfusion induces neuronal death through oxidative stress and neuronal zinc (Zn2+) dyshomeostasis. Glutathione (GSH) plays an important role in protecting neurons against oxidative stress as a major intracellular antioxidant. In addition, the thiol group of GSH can function as a principal Zn2+ chelator for the maintenance of Zn2+ homeostasis in neurons. These lines of evidence suggest that neuronal GSH levels could be a key factor in post-stroke neuronal survival. In neurons, excitatory amino acid carrier 1 (EAAC1) is involved in the influx of cysteine, and intracellular cysteine is the rate-limiting substrate for the synthesis of GSH. Recently, several studies have indicated that cysteine uptake through EAAC1 suppresses ischemia-induced neuronal death via the promotion of hippocampal GSH synthesis in ischemic animal models. In this article, we aimed to review and describe the role of GSH in hippocampal neuroprotection after ischemia/reperfusion, focusing on EAAC1.

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.

scholarly journals Meta-Analysis of Oxidative Transcriptomes in Insects

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 345
Author(s):  
Hidemasa Bono
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Meta Analysis ◽  
Adherens Junction ◽  
Enrichment Analysis ◽  
Oxidative Stress Response ◽  
Insect Species ◽  
Rna Seq ◽  
Manual Curation ◽  
Analysis Workflow

Data accumulation in public databases has resulted in extensive use of meta-analysis, a statistical analysis that combines the results of multiple studies. Oxidative stress occurs when there is an imbalance between free radical activity and antioxidant activity, which can be studied in insects by transcriptome analysis. This study aimed to apply a meta-analysis approach to evaluate insect oxidative transcriptomes using publicly available data. We collected oxidative stress response-related RNA sequencing (RNA-seq) data for a wide variety of insect species, mainly from public gene expression databases, by manual curation. Only RNA-seq data of Drosophila melanogaster were found and were systematically analyzed using a newly developed RNA-seq analysis workflow for species without a reference genome sequence. The results were evaluated by two metric methods to construct a reference dataset for oxidative stress response studies. Many genes were found to be downregulated under oxidative stress and related to organ system process (GO:0003008) and adherens junction organization (GO:0034332) by gene enrichment analysis. A cross-species analysis was also performed. RNA-seq data of Caenorhabditis elegans were curated, since no RNA-seq data of insect species are currently available in public databases. This method, including the workflow developed, represents a powerful tool for deciphering conserved networks in oxidative stress response.

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.

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