scholarly journals Bromofatty aldehyde derived from bromine exposure and myeloperoxidase and eosinophil peroxidase modify GSH and protein

2018 ◽  
Vol 59 (4) ◽  
pp. 696-705 ◽  
Author(s):  
Mark A. Duerr ◽  
Elisa N. D. Palladino ◽  
Celine L. Hartman ◽  
James A. Lambert ◽  
Jacob D. Franke ◽  
...  
Keyword(s):  
Phorbol Myristate Acetate ◽  
Plasma Levels ◽  
Adduct Formation ◽  
Nucleophilic Attack ◽  
Fatty Aldehyde ◽  
Myristate Acetate ◽  
Protein Adduct ◽  
Protein Thiols ◽  
Hypobromous Acid ◽  
Activated Neutrophils

α-Chlorofatty aldehydes (α-ClFALDs) and α-bromofatty aldehydes (α-BrFALDs) are produced in activated neutrophils and eosinophils. This study investigated the ability of α-BrFALD and α-ClFALD to react with the thiols of GSH and protein cysteinyl residues. Initial studies showed that 2-bromohexadecanal (2-BrHDA) and 2-chlorohexadecanal (2-ClHDA) react with GSH producing the same fatty aldehyde-GSH adduct (FALD-GSH). In both synthetic and cellular reactions, FALD-GSH production was more robust with 2-BrHDA compared with 2-ClHDA as precursor. NaBr-supplemented phorbol myristate acetate (PMA)-activated neutrophils formed more α-BrFALD and FALD-GSH compared with non-NaBr-supplemented neutrophils. Primary human eosinophils, which preferentially produce hypobromous acid and α-BrFALD, accumulated FALD-GSH following PMA stimulation. Mice exposed to Br2 gas had increased levels of both α-BrFALD and FALD-GSH in the lungs, as well as elevated systemic plasma levels of FALD-GSH in comparison to mice exposed to air. Similar relative reactivity of α-ClFALD and α-BrFALD with protein thiols was shown using click analogs of these aldehydes. Collectively, these data demonstrate that GSH and protein adduct formation are much greater as a result of nucleophilic attack of cysteinyl residues on α-BrFALD compared with α-ClFALD, which was observed in both primary leukocytes and in mice exposed to bromine gas.

scholarly journals NADPH Oxidase-dependent Oxidation and Externalization of Phosphatidylserine during Apoptosis in Me2SO-differentiated HL-60 Cells

2002 ◽  
Vol 277 (51) ◽  
pp. 49965-49975 ◽  
Author(s):  
Antonio Arroyo ◽  
Martin Modrianský ◽  
F. Behice Serinkan ◽  
Rosario I. Bello ◽  
Tatsuya Matsura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Nadph Oxidase ◽  
Phorbol Myristate Acetate ◽  
Oxidase Activity ◽  
Caspase 3 ◽  
Myristate Acetate ◽  
Phosphatidylserine Externalization ◽  
Activated Neutrophils ◽  
Stimulation Of

Resolution of inflammation requires clearance of activated neutrophils by phagocytes in a manner that protects adjacent tissues from injury. Mechanisms governing apoptosis and clearance of activated neutrophils from inflamed areas are still poorly understood. We used dimethylsulfoxide-differentiated HL-60 cells showing inducible oxidase activity to study NADPH oxidase-induced apoptosis pathways typical of neutrophils. Activation of the NADPH oxidase by phorbol myristate acetate caused oxidative stress as shown by production of superoxide and hydrogen peroxide, depletion of intracellular glutathione, and peroxidation of all three major classes of membrane phospholipids, phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine. In addition, phorbol myristate acetate stimulation of the NADPH oxidase caused apoptosis, as evidenced by apoptosis-specific phosphatidylserine externalization, increased caspase-3 activity, chromatin condensation, and nuclear fragmentation. Furthermore, phorbol myristate acetate stimulation of the NADPH oxidase caused recognition and ingestion of dimethylsulfoxide-differentiated HL-60 cells by J774A.1 macrophages. To reveal the apoptosis-related component of oxidative stress in the phorbol myristate acetate-induced response, we pretreated cells with a pancaspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (z-VAD-fmk), and found that it caused partial inhibition of hydrogen peroxide formation as well as selective protection of only phosphatidylserine, whereas more abundant phospholipids, phosphatidylcholine and phosphatidylethanolamine, were oxidized to the same extent in the absence or presence of z-VAD-fmk. In contrast, inhibitors of NADPH oxidase activity, diphenylene iodonium and staurosporine, as well as antioxidant enzymes, superoxide dismutase/catalase, completely protected all phospholipids against peroxidation, inhibited expression of apoptotic biomarkers and externalization of phosphatidylserine, and reduced phagocytosis of differentiated HL-60 cells by J774A.1 macrophages. Similarly, zymosan-induced activation of the NADPH oxidase resulted in the production of superoxide and oxidation of different classes of phospholipids of which only phosphatidylserine was protected by z-VAD-fmk. Accordingly, zymosan caused apoptosis in differentiated HL-60 cells, as evidenced by caspase-3 activation and phosphatidylserine externalization. Finally, zymosan triggered caspase-3 activation and extensive SOD/catalase-inhibitable phosphatidylserine exposure in human neutrophils. Overall, our results indicate that NADPH oxidase-induced oxidative stress in neutrophil-like cells triggers apoptosis and subsequent recognition and removal of these cells through pathways dependent on oxidation and externalization of phosphatidylserine.

Probing the Paradigm of Promiscuity for N‐Heterocyclic Carbene Complexes and their Protein Adduct Formation

2021 ◽  
Author(s):  
Matthew P. Sullivan ◽  
Monika Cziferszky ◽  
Iogann Tolbatov ◽  
Dianna Truong ◽  
Davide Mercadante ◽  
...  
Keyword(s):  
Adduct Formation ◽  
Carbene Complexes ◽  
Protein Adduct

Probing the Paradigm of Promiscuity for N‐Heterocyclic Carbene Complexes and their Protein Adduct Formation

2021 ◽  
Author(s):  
Matthew P. Sullivan ◽  
Monika Cziferszky ◽  
Iogann Tolbatov ◽  
Dianna Truong ◽  
Davide Mercadante ◽  
...  
Keyword(s):  
Adduct Formation ◽  
Carbene Complexes ◽  
Protein Adduct

Effects of thrombin, phorbol myristate acetate and prostaglandin D2 on 40-41 kDa protein that is ADP ribosylated by pertussis toxin in platelets

FEBS Letters ◽  
1986 ◽  
Vol 204 (2) ◽  
pp. 341-346 ◽  
Author(s):  
Stephen P. Halenda ◽  
Mario Volpi ◽  
George B. Zavoico ◽  
Ramadan I. Sha'afi ◽  
Maurice B. Feinstein
Keyword(s):  
Phorbol Myristate Acetate ◽  
Pertussis Toxin ◽  
Prostaglandin D2 ◽  
Myristate Acetate
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