Angeli's salt (Na₂N₂O₃) decomposes into nitroxyl (HNO) and nitrite (NO₂(-)), compounds of physiological and therapeutic interest for their impact on biological signaling both through nitric oxide and nitric oxide independent pathways. Both nitrite and HNO oxidize oxygenated hemoglobin to methemoglobin. Earlier work has shown that HNO catalyzes the reduction of nitrite by deoxygenated hemoglobin. In this work, we have shown that HNO accelerates the oxidation of oxygenated hemoglobin by NO₂(-). We have demonstrated this HNO mediated acceleration of the nitrite/oxygenated hemoglobin reaction with oxygenated hemoglobin being in excess to HNO and nitrite (as would be found under physiological conditions) by monitoring the formation of methemoglobin in the presence of Angeli's salt with and without added NO₂(-). In addition, this acceleration has been demonstrated using the HNO donor 4-nitrosotetrahydro-2H-pyran-4-yl pivalate, a water-soluble acyloxy nitroso compound that does not release NO₂(-) but generates HNO in the presence of esterase. This HNO donor was used both with and without NO₂(-) and acceleration of the NO₂(-) induced formation of methemoglobin was observed. We found that the acceleration was not substantially affected by catalase, superoxide dismutase, c-PTIO, or IHP, suggesting that it is not due to formation of extramolecular peroxide, NO₂ or H₂O₂, or to modulation of allosteric properties. In addition, we found that the acceleration is not likely to be related to HNO binding to free reduced hemoglobin, as we found HNO binding to reduced hemoglobin to be much weaker than has previously been proposed. We suggest that the mechanism of the acceleration involves local propagation of autocatalysis in the nitrite-oxygenated Hb reaction. This acceleration of the nitrite oxyhemoglobin reaction could affect studies aimed at understanding physiological roles of HNO and perhaps nitrite and use of these agents in therapeutics such as hemolytic anemias, heart failure, and ischemia reperfusion injury.
Angeli's salt (Na₂N₂O₃) decomposes into n class="Chemical">nitroxyl (HNO) and nitrite (NO₂(-)), compounds of physiological and therapeutic interest for their impact on biological signaling both through nitric oxide and nitric oxide independent pathways. Both nitrite and HNO oxidize oxygenated hemoglobin to methemoglobin. Earlier work has shown that HNO catalyzes the reduction of nitrite by deoxygenated hemoglobin. In this work, we have shown that HNO accelerates the oxidation of oxygenated hemoglobin by NO₂(-). We have demonstrated this HNO mediated acceleration of the nitrite/oxygenated hemoglobin reaction with oxygenated hemoglobin being in excess to HNO and nitrite (as would be found under physiological conditions) by monitoring the formation of methemoglobin in the presence of Angeli's salt with and without added NO₂(-). In addition, this acceleration has been demonstrated using the HNOdonor4-nitrosotetrahydro-2H-pyran-4-yl pivalate, a water-soluble acyloxy nitroso compound that does not release NO₂(-) but generates HNO in the presence of esterase. This HNOdonor was used both with and without NO₂(-) and acceleration of the NO₂(-) induced formation of methemoglobin was observed. We found that the acceleration was not substantially affected by catalase, superoxide dismutase, c-PTIO, or IHP, suggesting that it is not due to formation of extramolecular peroxide, NO₂ or H₂O₂, or to modulation of allosteric properties. In addition, we found that the acceleration is not likely to be related to HNO binding to free reduced hemoglobin, as we found HNO binding to reduced hemoglobin to be much weaker than has previously been proposed. We suggest that the mechanism of the acceleration involves local propagation of autocatalysis in the nitrite-oxygenated Hb reaction. This acceleration of the nitrite oxyhemoglobin reaction could affect studies aimed at understanding physiological roles of HNO and perhaps nitrite and use of these agents in therapeutics such ashemolytic anemias, heart failure, and ischemia reperfusion injury.
Authors: Kris T Huang; Agnes Keszler; Neil Patel; Rakesh P Patel; Mark T Gladwin; Daniel B Kim-Shapiro; Neil Hogg Journal: J Biol Chem Date: 2005-04-18 Impact factor: 5.157
Authors: Sruti Shiva; Zhi Huang; Rozalina Grubina; Junhui Sun; Lorna A Ringwood; Peter H MacArthur; Xiuli Xu; Elizabeth Murphy; Victor M Darley-Usmar; Mark T Gladwin Journal: Circ Res Date: 2007-02-09 Impact factor: 17.367
Authors: Nazareno Paolocci; Matthew I Jackson; Brenda E Lopez; Katrina Miranda; Carlo G Tocchetti; David A Wink; Adrian J Hobbs; Jon M Fukuto Journal: Pharmacol Ther Date: 2006-11-29 Impact factor: 12.310
Authors: Mark R Duranski; James J M Greer; Andre Dejam; Sathya Jaganmohan; Neil Hogg; William Langston; Rakesh P Patel; Shaw-Fang Yet; Xunde Wang; Christopher G Kevil; Mark T Gladwin; David J Lefer Journal: J Clin Invest Date: 2005-04-14 Impact factor: 14.808
Authors: Nathan S Bryan; Bernadette O Fernandez; Selena M Bauer; Maria Francisca Garcia-Saura; Alexandra B Milsom; Tienush Rassaf; Ronald E Maloney; Ajit Bharti; Juan Rodriguez; Martin Feelisch Journal: Nat Chem Biol Date: 2005-09-18 Impact factor: 15.040
Authors: Emilse Bermejo; Daniel A Sáenz; Fabiana Alberto; Ruth E Rosenstein; Sara E Bari; María A Lazzari Journal: Thromb Haemost Date: 2005-09 Impact factor: 5.249
Authors: Katrina M Miranda; Nazareno Paolocci; Tatsuo Katori; Douglas D Thomas; Eleonora Ford; Michael D Bartberger; Michael G Espey; David A Kass; Martin Feelisch; Jon M Fukuto; David A Wink Journal: Proc Natl Acad Sci U S A Date: 2003-07-15 Impact factor: 11.205
Authors: Nathan S Bryan; John W Calvert; John W Elrod; Susheel Gundewar; Sang Yong Ji; David J Lefer Journal: Proc Natl Acad Sci U S A Date: 2007-11-19 Impact factor: 11.205