scholarly journals Correlation between antibodies to bisphenol A, its target enzyme protein disulfide isomerase and antibodies to neuron-specific antigens

2016 ◽  
Vol 37 (4) ◽  
pp. 479-484 ◽  
Author(s):  
Datis Kharrazian ◽  
Aristo Vojdani
Keyword(s):  
Bisphenol A ◽  
Protein Disulfide Isomerase ◽  
Enzyme Protein ◽  
Disulfide Isomerase ◽  
Specific Antigens ◽  
Protein Disulfide ◽  
Target Enzyme

Endoplasmic Reticulum Protein (ERp) 29 Binds As Strongly As Protein Disulfide Isomerase (PDI) to Bisphenol A

2014 ◽  
Vol 27 (4) ◽  
pp. 501-506 ◽  
Author(s):  
Yuka Miyake ◽  
Shoko Hashimoto ◽  
Yoshie Sasaki ◽  
Tomohiro Kudo ◽  
Ami Oguro ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Bisphenol A ◽  
Protein Disulfide Isomerase ◽  
Disulfide Isomerase ◽  
Endoplasmic Reticulum Protein ◽  
Protein Disulfide

scholarly journals Route Exploration and Synthesis of the Reported Pyridone-Based PDI Inhibitor STK076545

2020 ◽  
Author(s):  
Eric Greve ◽  
Sergey Lindeman ◽  
Chris Dockendorff
Keyword(s):  
Protein Disulfide Isomerase ◽  
Enzyme Protein ◽  
Allyl Ester ◽  
Disulfide Isomerase ◽  
X Ray ◽  
Surface Receptors ◽  
Promising Target ◽  
Biological Studies ◽  
Final Compound ◽  
Protein Disulfide

The enzyme protein disulfide isomerase (PDI) is essential for the correct folding of proteins and the activation of certain cell surface receptors, and is a promising target for the treatment of cancer and thrombotic conditions. A previous high-throughput screen identified the commercial compound STK076545 as a promising PDI inhibitor. To confirm its activity and support further biological studies, a resynthesis was pursued of the reported b-keto-amide with an N-alkylated pyridone at the a-position. Numerous conventional approaches were complicated by undesired fragmentations or rearrangements. However, a successful 5-step synthetic route was achieved using an aldol reaction with an a-pyridone allyl ester as a key step. An X-ray crystal structure of the final compound confirmed that the reported structure of STK076545 was achieved, however its lack of PDI activity and inconsistent spectral data suggest that the commercial structure was misassigned.

scholarly journals Bisphenol A Binds to Protein Disulfide Isomerase and Inhibits Its Enzymatic and Hormone-Binding Activities

Endocrinology ◽  
2006 ◽  
Vol 147 (6) ◽  
pp. 2773-2780 ◽  
Author(s):  
Toyoko Hiroi ◽  
Kazushi Okada ◽  
Susumu Imaoka ◽  
Mayuko Osada ◽  
Yoshihiko Funae
Keyword(s):  
Bisphenol A ◽  
Protein Disulfide Isomerase ◽  
Hormone Binding ◽  
Disulfide Isomerase ◽  
Protein Disulfide

Over-expression of protein disulfide isomerase reduces the release of growth hormone induced by bisphenol A and/or T3

2007 ◽  
Vol 278 (1-2) ◽  
pp. 44-51 ◽  
Author(s):  
Kazushi Okada ◽  
Susumu Imaoka ◽  
Shoko Hashimoto ◽  
Toyoko Hiroi ◽  
Yoshihiko Funae
Keyword(s):  
Growth Hormone ◽  
Bisphenol A ◽  
Protein Disulfide Isomerase ◽  
Disulfide Isomerase ◽  
Over Expression ◽  
Protein Disulfide

Platelet protein disulfide isomerase is localized in the dense tubular system and does not become surface expressed after activation

Blood ◽  
2009 ◽  
Vol 114 (21) ◽  
pp. 4738-4740 ◽  
Author(s):  
Hezder E. van Nispen tot Pannerden ◽  
Suzanne M. van Dijk ◽  
Vivian Du ◽  
Harry F. G. Heijnen
Keyword(s):  
Cell Surface ◽  
Protein Disulfide Isomerase ◽  
Active Conformation ◽  
Enzyme Protein ◽  
Disulfide Isomerase ◽  
Anionic Phospholipids ◽  
Platelet Protein ◽  
Activated Platelets ◽  
Tubular System ◽  
Protein Disulfide

Abstract Evidence is accumulating that circulating tissue factor (TF) contributes to the initiation of coagulation and the formation of fibrin. The majority of circulating TF is cryptic, and it has been suggested that close vicinity with anionic phospholipids on the cell surface increases the active conformation of TF. Two recent papers have shown that encryption of TF and initiation of coagulation are facilitated by the enzyme protein disulfide isomerase (PDI), possibly on the surface of activated platelets or endothelial cells. In this brief report, we demonstrate that the majority of PDI in platelets is intracellular where it is exclusively located in the dense tubular system. On activation, PDI remains confined to the intracellular stores of the dense tubular system and is neither released nor targeted to the cell surface. Similar results were obtained in endothelium where PDI remains exclusively localized in the endoplasmic reticulum, both at steady state and after thrombin stimulation.

scholarly journals The Associations between Immunological Reactivity to the Haptenation of Unconjugated Bisphenol A to Albumin and Protein Disulfide Isomerase with Alpha-Synuclein Antibodies

Toxics ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 26
Author(s):  
Datis Kharrazian ◽  
Martha Herbert ◽  
Aristo Vojdani
Keyword(s):  
Bisphenol A ◽  
Human Serum ◽  
Protein Misfolding ◽  
Protein Disulfide Isomerase ◽  
Alpha Synuclein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Disulfide Isomerase ◽  
Substantial Risk ◽  
Protein Disulfide ◽  
Increased Susceptibility

Patients with Parkinson’s disease (PD) have increased susceptibility to bisphenol A (BPA) exposure since they have an impaired biotransformation capacity to metabolize BPA. PD subjects have reduced levels of conjugated BPA compared to controls. Reduced ability to conjugate BPA provides increased opportunity for unconjugated BPA to bind to albumin in human serum and protein disulfide isomerase on neurons. Once unconjugated BPA binds to proteins, it changes the allosteric structure of the newly configured protein leading to protein misfolding and the ability of the newly configured protein to act as a neoantigen. Once this neoantigen is formed, the immune system produces antibodies against it. The goal of our research was to investigate associations between unconjugated BPA bound to human serum albumin (BPA–HSA) antibodies and alpha-synuclein antibodies and between Protein Disulfide Isomerase (PDI) antibodies and alpha-synuclein antibodies. Enzyme–linked immunosorbent assay was used to determine the occurrences of alpha-synuclein antibodies, antibodies to BPA–HSA adducts, and PDI antibodies in the sera of blood donors. Subjects that exhibited high levels of unconjugated BPA–HSA antibodies or PDI antibodies had correlations and substantial risk for also exhibiting high levels of alpha-synuclein antibodies (p < 0.0001). We conclude that there are significant associations and risks between antibodies to BPA–HSA adducts and PDI antibodies for developing alpha-synuclein antibodies.

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