Protein disulfide isomerase

Wilkinson, Bonney; Gilbert, Hiram F.

doi:10.1016/j.bbapap.2004.02.017

Cited by 541 publications

(544 citation statements)

References 184 publications

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“…Protein disulphide isomerase (PDI), a 57kD member of the thioredoxin superfamily of oxidoreductases, functions primarily within the endoplasmic reticulum as a protein folding catalyst and chaperone, by virtue of its ability to bring about the formation, reduction or isomerisation of disulphide bonds [3]. PDI also resides outside the endoplasmic reticulum, at a variety of sites which include the exofacial surface of the plasma membrane [4], where it is available for regulation of allosteric disulphide bonds in proteins of the haemostasis system.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of thiol isomerase activity diminishes endothelial activation of plasminogen, but not of protein C

Smith

Shah²,

Kamaludin

et al. 2015

Thrombosis Research

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Introduction: Cell surface thiol isomerase enzymes, principally protein disulphide isomerase (PDI), have emerged as important regulators of platelet function and tissue factor activation via their action on allosteric disulphide bonds. Allosteric disulphides are present in other haemostasis-related proteins, and we have therefore investigated whether thiol isomerase inhibition has any influence on two endothelial activities relevant to haemostatic regulation, namely activation of protein C and activation of plasminogen, with subsequent fibrinolysis.

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Section: Introductionmentioning

confidence: 99%

Inhibition of thiol isomerase activity diminishes endothelial activation of plasminogen, but not of protein C

Smith

Shah²,

Kamaludin

et al. 2015

Thrombosis Research

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“…The A subunit of AB 5 subtilase is a serine protease that cleaves GRP78 at a single site, resulting in its selective inactivation, thereby triggering death in the target cells. PDIs participate in the correct protein folding of newly synthesized proteins through the maintenance of proper disulfide bridges (94)(95)(96)(97). GRP78 is among the genes that are significantly up-regulated in response to subtoxic doses of 4-HNE, a lipid peroxidation-derived R, -unsaturated aldehyde that covalently modifies proteins during oxidative stress (98).…”

Section: Discussionmentioning

confidence: 99%

Identification of the Protein Targets of the Reactive Metabolite of Teucrin A in Vivo in the Rat

Druckova

Mernaugh

Ham

et al. 2007

Chem. Res. Toxicol.

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Covalent modification of proteins is associated with the toxicity of many electrophiles, and the identification of relevant in vivo protein targets is a desirable but challenging goal. Here, we describe a strategy for the enrichment of adducted proteins utilizing single-chain fragment variable (ScFv) antibodies selected using phage-display technology. Teucrin A is a furan-containing diterpenoid found in the herb germander that is primarily responsible for the herb's hepatotoxicity in rodents and humans following metabolic activation by cytochrome P450 enzymes. Conjugates of the 1,4-enedial derivative of teucrin A, its presumed toxic metabolite, with lysine-and cysteine-containing peptides were synthesized and used to select ScFvs from a rodent phage-displayed library, which recognized the terpenoid moiety of the teucrin-derived adducts. Immunoaffinity isolation of adducted proteins from rat liver homogenates following administration of a toxic dose of teucrin A afforded a family of proteins that were identified by liquid chromatography/tandem mass spectrometry. Of the 46 proteins identified in this study, most were of mitochondrial and endoplasmic reticulum origin. Several cytosolic proteins were found, as well as four peroxisomal and two secreted proteins. Using Ingenuity Pathway Analysis software, two significant networks involving the target genes were identified that had major functions in gene expression, small molecule biochemistry, and cellular function and maintenance. These included proteins involved in lipid, amino acid, and drug metabolism. This study illustrates the utility of chemically synthesized biological conjugates of reactive intermediates and the potential of the phage display technology for the generation of affinity reagents for the isolation of adducted proteins.

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“…PDI is an abundant resident of the endoplasmic reticulum, where it functions as a disulfide isomerase and chaperone to facilitate proper folding of nascent proteins. [44][45][46][47] Some evidence suggests that PDI may also be localized to the cell membrane in tumor cells and there modulate integrin-dependent adhesion and sensitivity to chemotherapy. [48][49][50] To examine whether PDI is immunogenic in cancer patients, we established an ELISA with recombinant full-length human protein and evaluated sera from 46 metastatic melanoma, 22 metastatic non-small cell lung carcinoma, 2 metastatic ovarian carcinoma, and 12 acute myeloid leukemia patients who were enrolled on phase I clinical trials of vaccination with irradiated, autologous tumor cells engineered to secrete GM-CSF.…”

Section: Pdi Is Immunogenic In Myeloid Leukemiamentioning

confidence: 99%