Dataset Information


Desferrioxamine inhibits protein tyrosine nitration: mechanisms and implications.

ABSTRACT: Tissues are exposed to exogenous and endogenous nitrogen dioxide ((·)NO(2)), which is the terminal agent in protein tyrosine nitration. Besides iron chelation, the hydroxamic acid (HA) desferrioxamine (DFO) shows multiple functionalities including nitration inhibition. To investigate mechanisms whereby DFO affects 3-nitrotyrosine (3-NT) formation, we utilized gas-phase (·)NO(2) exposures, to limit introduction of other reactive species, and a lung surface model wherein red cell membranes (RCM) were immobilized under a defined aqueous film. When RCM were exposed to ()NO(2) covered by +/- DFO: (i) DFO inhibited 3-NT formation more effectively than other HA and non-HA chelators; (ii) 3-NT inhibition occurred at very low[DFO] for prolonged times; and (iii) 3-NT formation was iron independent but inhibition required DFO present. DFO poorly reacted with (·)NO(2) compared to ascorbate, assessed via (·)NO(2) reactive absorption and aqueous-phase oxidation rates, yet limited 3-NT formation at far lower concentrations. DFO also inhibited nitration under aqueous bulk-phase conditions, and inhibited 3-NT generated by active myeloperoxidase "bound" to RCM. Per the above and kinetic analyses suggesting preferential DFO versus (·)NO(2) reaction within membranes, we conclude that DFO inhibits 3-NT formation predominantly by facile repair of the tyrosyl radical intermediate, which prevents (·)NO(2) addition, and thus nitration, and potentially influences biochemical functionalities.


PROVIDER: S-EPMC3462664 | BioStudies | 2012-01-01

REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC6529413 | BioStudies
1000-01-01 | S-EPMC6175094 | BioStudies
2013-01-01 | S-EPMC3761327 | BioStudies
2019-01-01 | S-EPMC7341442 | BioStudies
2016-01-01 | S-EPMC5133998 | BioStudies
2019-01-01 | S-EPMC6737991 | BioStudies
2009-01-01 | S-EPMC2774826 | BioStudies
2017-01-01 | S-EPMC5656043 | BioStudies
1000-01-01 | S-EPMC5117089 | BioStudies
2019-01-01 | S-EPMC6586993 | BioStudies