Oxidation of Iron-nitrosyl-hemoglobin by Dehydroascorbic Acid Releases Nitric Oxide to Form Nitrite in Human Erythrocytes†

Biochemistry ◽  
2008 ◽  
Vol 47 (9) ◽  
pp. 2989-2996 ◽  
Author(s):  
Nathawut Sibmooh ◽  
Barbora Piknova ◽  
Fabiola Rizzatti ◽  
Alan N. Schechter
Keyword(s):  
Nitric Oxide ◽  
Dehydroascorbic Acid ◽  
Human Erythrocytes ◽  
Iron Nitrosyl ◽  
Nitrosyl Hemoglobin

Potential of Angeli’s Salt To Reduce Nitric Oxide Scavenging in Hemolysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3788-3788
Author(s):  
Daniel B. Kim-Shapiro ◽  
Xiaojun He ◽  
Ivan Azarov ◽  
Jodi Richardson ◽  
S. Bruce King ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sickle Cell ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Cell Disease ◽  
Free Hemoglobin ◽  
Angeli's Salt ◽  
Iron Nitrosyl ◽  
Sickle Cell Crisis ◽  
No Bioavailability ◽  
Nitrosyl Hemoglobin

Abstract Since cell-free hemoglobin (Hb) scavenges nitric oxide (NO) more effectively than that encapsulated in the red blood cell (RBC), hemolysis reduces NO bioavailability with pathological consequences in sickle cell disease and other hemolytic anemias, paroxysmal nocturnal hemoglobinuria, thalassemia intermedia, malaria, and cardiopulomonary bypass. The ability of the cell-free Hb to scavenge NO is reduced when the Hb is converted from its oxygenated form (HbO2) to its oxidized form, methemoglobin (MetHb). We show that Angeli’s salt (AS) can convert two OxyHb to two MetHb molecules through its release of nitroxyl (HNO). AS also further converts the MetHb to less potentially oxidative forms: nitrite bound MetHb and iron-nitrosyl hemoglobin. We also show that, due to the fast reactivity of HNO with Hb (like NO), AS preferentially reacts with cell-free rather than RBC encapsulated Hb. In conditions simulating sickle cell crisis, within six minutes, AS converted 45 ± 12% of cell-free Hb to non-NO scavenging forms (MetHb and iron-nitrosyl Hb) and only converted 0.4 ± 0.3% of RBC encapsulated Hb (n=3). Similar preferential reactivity was observed under other physiologically relevant conditions. We conclude that, as AS preferentially reacts with cell-free Hb compared to RBC encapsulated Hb, converting it to species that do not effectively scavenge NO, it is has promise as a treatment for increasing NO biavailability in conditions associated with hemolysis.

Dietary doses of nitrite restore circulating nitric oxide level and improve renal injury in l-NAME-induced hypertensive rats

2008 ◽  
Vol 295 (5) ◽  
pp. F1457-F1462 ◽  
Author(s):  
Yasuhisa Kanematsu ◽  
Kunihisa Yamaguchi ◽  
Hideki Ohnishi ◽  
Yuki Motobayashi ◽  
Keisuke Ishizawa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Injury ◽  
Low Dose ◽  
Tap Water ◽  
Chronic Administration ◽  
High Dose ◽  
Hypertensive Rats ◽  
Iron Nitrosyl ◽  
Nitrosyl Hemoglobin ◽  
Medium Dose

We have reported that pharmacological doses of oral nitrite increase circulating nitric oxide (NO) and exert hypotensive effects in Nω-nitro-l-arginine methyl ester (l-NAME)-induced hypertensive rats. In this study, we examined the effect of a chronic dietary dose of nitrite on the hypertension and renal damage induced by chronic l-NAME administration in rats. The animals were administered tap water containing l-NAME (1 g/l) or l-NAME + nitrite (low dose: 0.1 mg/l, medium dose: 1 mg/l, high dose: 10 mg/l) for 8 wk. We evaluated blood NO levels as hemoglobin-NO adducts (iron-nitrosyl-hemoglobin), using an electron paramagnetic resonance method. Chronic administration of l-NAME for 8 wk induced hypertension and renal injury and reduced the blood iron-nitrosyl-hemoglobin level (control 38.8 ± 8.9 vs. l-NAME 6.0 ± 3.1 arbitrary units). Coadministration of a low dose of nitrite with l-NAME did not change the reduced iron-nitrosyl-hemoglobin signal and did not improve the l-NAME-induced renal injury. The blood iron-nitrosyl-hemoglobin signals of the medium dose and high dose of nitrite were significantly higher than that of l-NAME alone. Chronic administration of a medium dose of nitrite attenuated l-NAME-induced renal histological changes and proteinuria. A high dose of nitrite also attenuated l-NAME-induced renal injury. These findings suggest that dietary doses of nitrite that protect the kidney are associated with significant increase in iron-nitrosyl-hemoglobin levels. We conclude that dietary nitrite-derived NO generation may serve as a backup system when the nitric oxide synthase/l-arginine-dependent NO generation system is compromised.

The reduction of dehydroascorbic acid by human erythrocytes

1956 ◽  
Vol 1 (6) ◽  
pp. 557-569 ◽  
Author(s):  
L. Christine ◽  
G. Thomson ◽  
Betty Iggo ◽  
A.C. Brownie ◽  
C.P. Stewart
Keyword(s):  
Dehydroascorbic Acid ◽  
Human Erythrocytes

scholarly journals Nitric oxide interactions with cobalamins: biochemical and functional consequences

Blood ◽  
1996 ◽  
Vol 88 (5) ◽  
pp. 1857-1864 ◽  
Author(s):  
M Brouwer ◽  
W Chamulitrat ◽  
G Ferruzzi ◽  
DL Sauls ◽  
JB Weinberg
Keyword(s):  
Nitric Oxide ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Resonance Spectroscopy ◽  
Paramagnetic Resonance ◽  
No Formation ◽  
Iron Nitrosyl ◽  
Wide Range ◽  
Functional Consequences

Abstract Nitric oxide (NO) is a paramagnetic gas that has been implicated in a wide range of biologic functions. The common pathway to evoke the functional response frequently involves the formation of an iron- nitrosyl complex in a target (heme) protein. In this study, we report on the interactions between NO and cobalt-containing vitamin B12 derivatives. Absorption spectroscopy showed that of the four Co(III) derivatives (cyanocobalamin [CN-Cbl], aquocobalamin [H2O-Cbl], adenosylcobalamin [Ado-Cbl], and methylcobalamin [MeCbl]), only the H2O- Cbl combined with NO. In addition, electron paramagnetic resonance spectroscopy of H2O-Cbl preparations showed the presence of a small amount of Cob-(II)alamin that was capable of combining with NO. The Co(III)-NO complex was very stable, but could transfer its NO moiety to hemoglobin (Hb). The transfer was accompanied by a reduction of the Co(III) to Co(II), indicating that NO+ (nitrosonium) was the leaving group. In accordance with this, the NO did not combine with the Hb Fe(II)-heme, but most likely with the Hb cysteine-thiolate. Similarly, the Co(III)-NO complex was capable of transferring its NO to glutathione. Ado-Cbl and Me-Cbl were susceptible to photolysis, but CN- Cbl and H2O-Cbl were not. The homolytic cleavage of the Co(III)-Ado or Co(III)-Me bond resulted in the reduction of the metal. When photolysis was performed in the presence of NO, formation of NO-Co(II) was observed. Co(II)-nitrosyl oxidized slowly to form Co(III)-nitrosyl. The capability of aquocobalamin to combine with NO had functional consequences. We found that nitrosylcobalamin had diminished ability to serve as a cofactor for the enzyme methionine synthase, and that aquocobalamin could quench NO-mediated inhibition of cell proliferation. Our in vitro studies therefore suggest that interactions between NO and cobalamins may have important consequences in vivo.

scholarly journals Turn-on fluorescent probes for nitric oxide sensing based on the ortho-hydroxyamino structure showing no interference with dehydroascorbic acid

2014 ◽  
Vol 50 (27) ◽  
pp. 3579 ◽  
Author(s):  
Alicia Beltrán ◽  
M. Isabel Burguete ◽  
Daniel R. Abánades ◽  
Dolores Pérez-Sala ◽  
Santiago V. Luis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fluorescent Probes ◽  
Dehydroascorbic Acid ◽  
Turn On

scholarly journals Nitrosylation of Nitric-Oxide-Sensing Regulatory Proteins Containing [4Fe-4S] Clusters Gives Rise to Multiple Iron-Nitrosyl Complexes

2016 ◽  
Vol 128 (47) ◽  
pp. 14795-14799 ◽  
Author(s):  
Pauline N. Serrano ◽  
Hongxin Wang ◽  
Jason C. Crack ◽  
Christopher Prior ◽  
Matthew I. Hutchings ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Regulatory Proteins ◽  
Nitrosyl Complexes ◽  
Iron Nitrosyl ◽  
Iron Nitrosyl Complexes

Ascorbic Acid Catalyzes Nitric Oxide Production from Nitrite Ions.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1574-1574 ◽  
Author(s):  
Nathawut Sibmooh ◽  
Barbora Piknova ◽  
Alan N. Schechter
Keyword(s):  
Nitric Oxide ◽  
Ascorbic Acid ◽  
Rate Constant ◽  
Dehydroascorbic Acid ◽  
Nitrite Reduction ◽  
Erythrocyte Membranes ◽  
No Production ◽  
Ferrous Ions ◽  
Physiological Conditions ◽  
Ferrous Heme

Abstract We have previously shown that nitrite ions can be reduced by hemoglobin to nitric oxide (NO), a ubiquitous signaling molecule and potent vasodilator. Nitrite serves as a stable tissue and vascular source for NO production; the reduction reaction is maximal at about 50% oxygen saturation values and is enhanced at low pH but little is known about other effectors of this reaction. In the current work, we studied the effect of ascorbic acid on nitrite reduction under physiological conditions using chemiluminescence to quantify NO production. In physiological buffer, this reaction has a rate constant of about 1×10−5 M−1.s−1. Thus, a significant production of NO would likely occur in plasma only at pharmacological levels of ascorbic acid (> 1 mM) although lowering pH below 7.0 markedly enhances this reaction. Loading human erythrocytes with 0.5 mM dehydroascorbic acid, which is in redox equilibrium with ascorbic acid and which can significantly raise intracellular ascorbic acid levels, increased basal levels of nitrite ions from 42±9.0 nM to 98±56 nM. Uptake of nitrite ions into erythrocytes by incubation in 10 μM nitrite was increased about 1.5 fold by dehydroascorbic acid and the half-time of nitrite loss was slowed to the same extent. Ascorbic acid also reduced free ferric heme in erythrocytes and plasma to ferrous heme which catalyzed the reduction of nitrite to NO with a rate constant of 2.3×103 M−1.s−1 under physiological conditions. However, free ferrous ions did not significantly produce NO in physiological buffer (rate constant = 1.8×10−2 M−1.s−1). The reaction of ferrous heme with nitrite was not affected by heme binding to proteins such as hemopexin and albumin, or erythrocyte membranes. These results suggest that physiological levels of ascorbic acid (20–80 μM in plasma and erythrocytes) may act to catalyze NO production in the blood by promoting the reduction of nitrite ions by free ferrous heme and by increasing intra-erythrocytic levels of nitrite ions which can be reduced to NO by deoxyhemoglobin.

Increased l-arginine Transport in Human Erythrocytes in Chronic Heart Failure

1998 ◽  
Vol 94 (1) ◽  
pp. 43-48 ◽  
Author(s):  
H. Hanssen ◽  
T. M. C. Brunini ◽  
M. Conway ◽  
A. P. Banning ◽  
N. B. Roberts ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Human Erythrocytes ◽  
Transport Systems ◽  
Acid Transport ◽  
Cationic Amino Acid ◽  
Arginine Transport ◽  
Healthy Donors ◽  
Patients With Heart Failure

1. Transport of l-arginine was investigated under zero-trans conditions in human erythrocytes from healthy donors and patients with heart failure. 2. Saturable influx of l-arginine was mediated by the classical cationic amino acid transport systems y+ and y+L. 3. The Vmax for l-arginine transport via system y+ increased from 292 to 490 μmol h−-1 l−-1 of cells in heart failure. 4. With system y+ inhibited by N-ethylmaleimide (0.2 mmol/l), the Vmax for the transport of l-arginine via system y+L was unaffected in erythrocytes from patients with heart failure. 5. The inhibition of l-arginine and l-leucine influx by NG-monomethyl-l-arginine was similar in erythrocytes from control and heart failure patients. 6. Plasma l-arginine levels were reduced in patients with heart failure (59 μmol/l) compared with controls (125 μmol/l). Plasma from patients with heart failure also contained the endogenous l-arginine analogue NG-monomethyl-l-arginine, which was undetectable in plasma from controls. 7. Intracellular concentrations of l-arginine and NG-monomethyl-l-arginine were significantly elevated in erythrocytes from patients with heart failure compared with controls, consistent with an increased transport capacity for l-arginine and NG-monomethyl-l-arginine. 8. The present study provides the first evidence that system y+ mediates the increased transport of l-arginine in human erythrocytes from patients with chronic heart failure. These findings are similar to our previous results obtained in patients with chronic renal failure. Since both pathologies seem to present with an increased synthesis of nitric oxide, studies of l-arginine transport in erythrocytes may provide a valuable paradigm to study abnormalities of the l-arginine-nitric oxide signalling pathway.

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