Redox-mediated mechanisms and biological responses of copper-catalyzed reduction of the nitrite ion in vitro.

Abstract

During ischemia nitrite may be converted into nitric oxide (NO) by reaction with heme-carrying proteins or thiol-containing enzymes. NO acts as a regulator of vasodilation and protector against oxidative stress-induced tissue injuries. As a result of ischemia-induced oxidative stress, hypoxia and/or acidosis bivalent copper ions (Cu(2+)) can dissociate from their physiological carrier proteins. Reduced by the body's own antioxidants, the resultant Cu(1+) might represent an effective reductant of nitrite. Here we have evaluated in vitro copper-dissociation from copper/BSA (bovine serum albumin) complexes under ischemic conditions. Furthermore, using physiological concentrations, we have characterized the capacity of antioxidants and bivalent copper ions to serve as Cu(1+)-agitated catalytic sites for nitrite reduction and also the biological responses of this mechanism in vitro. We found that as a consequence of an acidic milieu and/or oxidative stress the copper-binding capacity of serum albumin strongly declined, leading to significant dissociation of copper ions into the ambient solution. At physiologically relevant pH-values Cu(2+) ions in combination with physiologically available copper reductants (i.e., ascorbate, glutathione, Fe(2+)) significantly enhanced nitrite reduction and subsequent non-enzymatic NO generation under hypoxic but also normoxic conditions. Our data demonstrate for the first time that upon ischemic conditions carrier protein-dissociated copper ions combined with appropriate reductants may serve as Cu(1+)-driven catalytic sites for nitrite reduction, leading to the formation of biologically relevant NO formation. Thus, in addition to the action of heme proteins, copper-catalyzed non-enzymatic NO formation from nitrite might represent a further physiologically relevant vasodilating and NO-dependent protective principle to ischemic stress.

• Authors: Christian Opländer, Julian Rösner, Alexander Gombert, Alexander Brodski, Tatsiana Suvorava, Vera Grotheer, Ernst E van Faassen, Klaus-Dietrich Kröncke, Georg Kojda, Joachim Windolf, Christoph V Suschek
• Journal: Nitric oxide : biology and chemistry (Nitric Oxide) Vol. 35 Pg. 152-64 (Nov 30 2013) ISSN: 1089-8611 [Electronic] United States
• PMID: 24140456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Nitrites
• Serum Albumin, Bovine
• Nitric Oxide
• Copper
• Ascorbic Acid
• Oxygen

Topics

• Animals
• Antioxidants (chemistry)
• Aorta (chemistry, metabolism)
• Ascorbic Acid
• Cattle
• Cell Line
• Copper (chemistry, metabolism)
• Humans
• Hydrogen-Ion Concentration
• Nitric Oxide (chemistry, metabolism)
• Nitrites (chemistry, metabolism)
• Oxidation-Reduction
• Oxidative Stress (physiology)
• Oxygen (analysis)
• Rats
• Serum Albumin, Bovine (chemistry, metabolism)
• Swine