The Balancing of Peroxynitrite Detoxification between Ferric Heme-Proteins and CO₂: The Case of Zebrafish Nitrobindin

• Main Authors: Giovanna De Simone (Author), Andrea Coletta (Author), Alessandra di Masi (Author), Massimo Coletta (Author), Paolo Ascenzi (Author)
• Format: Book
• Published: MDPI AG, 2022-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Nitrobindins (Nbs) are all-β-barrel heme proteins and are present in prokaryotes and eukaryotes. Although their function(s) is still obscure, Nbs trap NO and inactivate peroxynitrite. Here, the kinetics of peroxynitrite scavenging by ferric <i>Danio rerio</i> Nb (<i>Dr</i>-Nb(III)) in the absence and presence of CO₂ is reported. The <i>Dr</i>-Nb(III)-catalyzed scavenging of peroxynitrite is facilitated by a low pH, indicating that the heme protein interacts preferentially with peroxynitrous acid, leading to the formation of nitrate (~91%) and nitrite (~9%). The physiological levels of CO₂ dramatically facilitate the spontaneous decay of peroxynitrite, overwhelming the scavenging activity of <i>Dr</i>-Nb(III). The effect of <i>Dr</i>-Nb(III) on the peroxynitrite-induced nitration of L-tyrosine was also investigated. <i>Dr</i>-Nb(III) inhibits the peroxynitrite-mediated nitration of free L-tyrosine, while, in the presence of CO₂, <i>Dr</i>-Nb(III) does not impair nitro-L-tyrosine formation. The comparative analysis of the present results with data reported in the literature indicates that, to act as efficient peroxynitrite scavengers in vivo, i.e., in the presence of physiological levels of CO₂, the ferric heme protein concentration must be higher than 10⁻⁴ M. Thus, only the circulating ferric hemoglobin levels appear to be high enough to efficiently compete with CO₂/HCO₃⁻ in peroxynitrite inactivation. The present results are of the utmost importance for tissues, like the eye retina in fish, where blood circulation is critical for adaptation to diving conditions.

Item Description

10.3390/antiox11101932
2076-3921