Protein disulfide isomerase mediates glutathione depletion-induced cytotoxicity

Okada, Kazushi; Fukui, Masayuki; Zhu, Bao‐Ting

doi:10.1016/j.bbrc.2016.06.066

Cited by 25 publications

(28 citation statements)

References 30 publications

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“…GPx catalyzes the reduction of hydroperoxides (ROOH) to water, using glutathione (GSH) as the reductant. P4HB also participates in the process by mediating homeostasis of the antioxidant glutathione [38]. However, we did not identify E/S proteins in the Cytochrome P450 (CYP450) family in phase III detoxification.…”

Section: Genome-wide Host-parasite Interaction Analysismentioning

confidence: 78%

High-quality reference genome ofFasciola gigantica: Insights into the genomic signatures of transposon-mediated evolution and specific parasitic adaption in tropical regions

Luo

Cui

Wang

et al. 2021

Preprint

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Fasciola gigantica and Fasciola hepatica are causative pathogens of fascioliasis , with the widest latitudinal, longitudinal, and altitudinal distribution; however, among parasites, they have the largest sequenced genomes, hindering genomic research. In the present study, we used various sequencing and assembly technologies to generate a new high-quality Fasciola gigantica reference genome. We improved the integration of gene structure prediction, and identified two independent transposable element expansion events contributing to (1) the speciation between Fasciola and Fasciolopsis during the Cretaceous-Paleogene boundary mass extinction, and (2) the habitat switch to the liver during the Paleocene-Eocene Thermal Maximum , accompanied by gene length increment. Long interspersed element (LINE) duplication contributed to the second transposon-mediated alteration, showing an obvious trend of insertion into gene regions, regardless of strong purifying selection. Gene ontology analysis of genes with long LINE insertions identified membrane-associated and vesicle secretion process proteins, further implicating the functional alteration of the gene network . We identified 852 excretory/secretory proteins and 3300 protein-protein interactions between Fasciola gigantica and its host. Among them, copper/zinc superoxide dismutase genes, with specific gene copy number variations, might play a central role in the phase I detoxification process. Analysis of 559 single-copy orthologs suggested that Fasciola gigantica and Fasciola hepatica diverged at 11.8 Ma near the Middle and Late Miocene Epoch boundary. We identified 98 rapidly evolving gene families, including actin and aquaporin, which might explain the large body size and the parasitic adaptive character resulting in these liver flukes becoming epidemic in tropical and subtropical regions.

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Section: Genome-wide Host-parasite Interaction Analysismentioning

confidence: 78%

High-quality reference genome ofFasciola gigantica: Insights into the genomic signatures of transposon-mediated evolution and specific parasitic adaption in tropical regions

Luo

Cui

Wang

et al. 2021

Preprint

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“…The ratio of glutathione (GSH) vs. glutathione disulfide (GSSG) is important for cellular physiology since a decreased GSH/GSSG ratio leads to increased susceptibility to oxidative stress whereas increased GSH levels induce resistance of cancer cells to oxidative stress ( 37 ). Inhibition of PDIA1 isomerase activity has been shown to abrogate glutathione depletion ( 8 ) indicating the essential role of PDIA1 in the process of disulfide bond formation and therefore the regulation of the ratio of GSH vs. GSSG ( 38 ). To investigate the role of PDIA1 in the regulation of the GSH homeostasis in breast cancer cells the GSH/GSSG ratio was investigated in MCF-7 and MDA-MB-231 cells in which the PDIA1 expression had been silenced.…”

Section: Resultsmentioning

confidence: 99%

“…Redox responsive endoplasmic reticulum proteins such as members of the protein disulfide isomerase (PDI) superfamily and in particular the prototype family member prolyl 4-hydroxylase subunit beta (P4HB or PDIA1) activates the ER transmembrane kinase protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) thus playing a crucial role in the stimulation of the UPR ( 7 ). PDIA1 has been shown to modulate cellular oxidative stress mediating homeostasis of the antioxidant glutathione ( 8 ) and its function is regulated by cellular redox state. Specifically, PDIA1 exerts chaperone and isomerase activities in an oxidative stress-dependent manner facilitating redox-mediated regulation of protein folding ( 9 – 12 ).…”

Section: Introductionmentioning

confidence: 99%

Protein disulfide isomerase A1 regulates breast cancer cell immunorecognition in a manner dependent on redox state

et al. 2020

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Oxidoreductase protein disulphide isomerases (PDI) are involved in the regulation of a variety of biological processes including the modulation of endoplasmic reticulum (ER) stress, unfolded protein response (UPR), ER-mitochondria communication and the balance between pro-survival and pro-death pathways. In the current study the role of the PDIA1 family member in breast carcinogenesis was investigated by measuring ROS generation, mitochondrial membrane disruption, ATP production and HLA-G protein levels on the surface of the cellular membrane in the presence or absence of PDIA1. The results showed that this enzyme exerted pro-apoptotic effects in estrogen receptor (ERα)-positive breast cancer MCF-7 and pro-survival in triple negative breast cancer (TNBC) MDA-MB-231 cells. ATP generation was upregulated in PDIA1 -silenced MCF-7 cells and downregulated in PDIA1 -silenced MDA-MB-231 cells in a manner dependent on the cellular redox status. Furthermore, MCF-7 and MDA-MB-231 cells in the presence of PDIA1 expressed higher surface levels of the non-classical human leukocyte antigen (HLA-G) under oxidative stress conditions. Evaluation of the METABRIC datasets showed that low PDIA1 and high HLA-G mRNA expression levels correlated with longer survival in both ERα-positive and ERα-negative stage 2 breast cancer patients. In addition, analysis of the PDIA1 vs. the HLA-G mRNA ratio in the subgroup of the living stage 2 breast cancer patients exhibiting low PDIA1 and high HLA-G mRNA levels revealed that the longer the survival time of the ratio was high PDIA1 and low HLA-G mRNA and occurred predominantly in ERα-positive breast cancer patients whereas in the same subgroup of the ERα-negative breast cancer mainly this ratio was low PDIA1 and high HLA-G mRNA. Taken together these results provide evidence supporting the view that PDIA1 is linked to several hallmarks of breast cancer pathways including the process of antigen processing and presentation and tumor immunorecognition.

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“…The enzymatic cellular redox system consists of a set of enzymes that generate ROS and reactive nitrogen species (RNS) and another set of antioxidant enzymes. TXNDC5 is an enzyme with protein disulphide isomerase (PDI) activity that can repair or correct protein conformation between reduced and oxidized thiol groups in oxidized proteins to prevent cell damage [ 11 ]. PRX IV can oxidize the thiol groups of PDI.…”

Section: Resultsmentioning

confidence: 99%

(+)-Aeroplysinin-1 Modulates the Redox Balance of Endothelial Cells

et al. 2018

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The bioactive natural compound from marine origin, (+)-aeroplysinin-1, has been shown to exhibit potent anti-inflammatory and anti-angiogenic effects. The aim of the present study was to identify new targets for (+)-aeroplysinin-1 in endothelial cells. The sequential use of 2D-electrophoresis and MALDI-TOF-TOF/MS allowed us to identify several differentially expressed proteins. Four of these proteins were involved in redox processes and were validated by Western blot. The effects of (+)-aeroplysinin-1 were further studied by testing the effects of the treatment with this compound on the activity of several anti- and pro-oxidant enzymes, as well as on transcription factors involved in redox homeostasis. Finally, changes in the levels of total reactive oxygen species and mitochondrial membrane potential induced by endothelial cell treatments with (+)-aeroplysinin-1 were also determined. Taken altogether, these findings show that (+)-aeroplysinin-1 has multiple targets involved in endothelial cell redox regulation.

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Protein disulfide isomerase mediates glutathione depletion-induced cytotoxicity

Cited by 25 publications

References 30 publications

High-quality reference genome ofFasciola gigantica: Insights into the genomic signatures of transposon-mediated evolution and specific parasitic adaption in tropical regions

High-quality reference genome ofFasciola gigantica: Insights into the genomic signatures of transposon-mediated evolution and specific parasitic adaption in tropical regions

Protein disulfide isomerase A1 regulates breast cancer cell immunorecognition in a manner dependent on redox state

(+)-Aeroplysinin-1 Modulates the Redox Balance of Endothelial Cells

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