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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Böhmer, Anke Pich, Andreas Schmidt, Mario Haghikia, Arash Tsikas, Dimitrios |
| Description | Country affiliation: Germany Author Affiliation: Böhmer A ( Centre of Pharmacology and Toxicology, Hannover Medical School, 30623 Hannover, Germany.); Pich A ( Institute of Toxicology and Core Unit Proteomics, Hannover Medical School, 30623 Hannover, Germany.); Schmidt M ( Centre of Pharmacology and Toxicology, Hannover Medical School, 30623 Hannover, Germany.); Haghikia A ( Department of Cardiology and Angiology, Hannover Medical School, 30623 Hannover, Germany.); Tsikas D ( Centre of Pharmacology and Toxicology, Hannover Medical School, 30623 Hannover, Germany. Electronic address: tsikas.dimitros@mh-hannover.de.) |
| Abstract | Previously we found by HPLC with fluorescence detection that inorganic nitrite induces oxidation of glutathione (GSH) to its disulfide (GSSG) in intact and more abundantly in lyzed red blood cells (RBCs) from healthy humans. In the present work, we performed MS-based protein analysis and observed that nitrite (range, 0-20mM) induces formation of S-glutathionyl hemoglobin (HbSSG) at cysteine (Cys) ß93 and ß112 of oxyhemoglobin (HbO2) in lyzed human RBCs (range, 6-8mM HbO2). Hemoglobin species were isolated from incubation mixtures of nitrite in lyzed RBCs by ultrafiltration or affinity chromatography and analyzed by HPLC and LC-MS/MS. The mechanism likely involves inhibition of catalase activity by nitrite (IC50, 9 µM), which allows H2O2 to accumulate and oxidize Cys moieties of oxyhemoglobin and erythrocytic GSH to form HbSSG in addition to GSSG. In freshly prepared hemolysate samples, nitrite induced release of superoxide and molecular oxygen. In the presence of paracetamol and nitrite in hemolysate samples, 3-nitro-paracetamol was detected. Nitrite also induced S-nitroso hemoglobin (HbSNO) formation in low yield (i.e., 0.1%). Synthetic cysteine (Cys), glutathione (GSH), N-acetylcysteine (NAC) and N-acetylcysteine ethyl ester (NACET) inhibited nitrite-induced modifications of oxyhemoglobin including methemoglobin, HbSSG (CysSH >> NACET >> GSH ≈ NAC; thiol concentration, 50 µM) and HbSNO. Nitrite-induced oxidative modifications may alter physiological hemoglobin functions and may require alternative treatments for conditions associated with oxidized hemoglobin like in nitrite-induced methemoglobinemia. Accumulation of soluble Cys in RBCs via oral administration of NACET could be a new promising strategy to prevent nitrite-induced methemoglobinemia by nitrite and other oxidants. |
| File Format | HTM / HTML |
| ISSN | 15700232 |
| Journal | Journal of Chromatography B |
| Volume Number | 1019 |
| e-ISSN | 1873376X |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2016-04-15 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine Analytical Chemistry Clinical Biochemistry Biochemistry |
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