Quantitative assessment of cyanide in cystic fibrosis sputum and its oxidative catabolism by hypochlorous acid
| Autor: | Brian M. Morrissey, Michele A. La Merrill, Carroll E. Cross, Sean Ott, Keri A. Hayakawa, Tamara Kadir, Jason P. Eiserich |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
Male 0301 basic medicine Cystic Fibrosis Hypochlorous acid Cyanide Biochemistry 03 medical and health sciences chemistry.chemical_compound Western blot Physiology (medical) medicine Humans Protein carbamoylation Electrodes Cyanides Protein Carbamylation medicine.diagnostic_test biology Catabolism Sputum Electrochemical Techniques Middle Aged Cyanate Hypochlorous Acid Kinetics 030104 developmental biology chemistry Myeloperoxidase Pseudomonas aeruginosa biology.protein Female Cobamides Oxidation-Reduction Protein Processing Post-Translational Cyanogen chloride |
| Zdroj: | Free Radical Biology and Medicine. 129:146-154 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2018.09.007 |
| Popis: | Rationale Cystic fibrosis (CF) patients are known to produce cyanide (CN-) although challenges exist in determinations of total levels, the precise bioactive levels, and specificity of its production by CF microflora, especially P. aeruginosa. Our objective was to measure total CN- levels in CF sputa by a simple and novel technique in P. aeruginosa positive and negative adult patients, to review respiratory tract (RT) mechanisms for the production and degradation of CN-, and to interrogate sputa for post-translational protein modification by CN- metabolites. Methods Sputa CN- concentrations were determined by using a commercially available CN- electrode, measuring levels before and after addition of cobinamide, a compound with extremely high affinity for CN-. Detection of protein carbamoylation was measured by Western blot. Measurements and main results The commercial CN- electrode was found to overestimate CN- levels in CF sputum in a highly variable manner; cobinamide addition rectified this analytical issue. Although P. aeruginosa positive patients tended to have higher total CN- values, no significant differences in CN- levels were found between positive and negative sputa. The inflammatory oxidant hypochlorous acid (HOCl) was shown to rapidly decompose CN-, forming cyanogen chloride (CNCl) and the carbamoylating species cyanate (NCO-). Carbamoylated proteins were found in CF sputa, analogous to reported findings in asthma. Conclusions Our studies indicate that CN- is a transient species in the inflamed CF airway due to multiple biosynthetic and metabolic processes. Stable metabolites of CN-, such as cyanate, or carbamoylated proteins, may be suitable biomarkers of overall CN- production in CF airways. |
| Databáze: | OpenAIRE |
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