scholarly journals Binding of nitric oxide to thiols and hemes in hemoglobin H: implications for α-thalassemia and hypertension

1997 ◽  
Vol 43 (8) ◽  
pp. 1442-1447 ◽  
Author(s):  
Poluru L Reddy ◽  
Lemuel J Bowie ◽  
Steven Callistein
Keyword(s):  
Nitric Oxide ◽  
Sulfhydryl Groups ◽  
Spectral Studies ◽  
Biochemical Basis

Abstract Our earlier studies suggested an association between α-thalassemia and hypertension. We postulated that this association might involve trapping of the vasodilator nitric oxide (NO) by hemoglobin (Hb). Hb A has recently been shown to carry NO on its sulfhydryl groups in addition to its hemes. In this report we studied the interaction of purified Hb H as well as Hb A with NO. The number of reactive sulfhydryls were determined spectrophotometrically with bis-dithionitrobenzoate. Spectral studies and nitrosothiol measurements after treatment with NO or nitrosothiols indicated that all eight reactive sulfhydryls of Hb H were capable of binding NO. Hb A, however, was only able to bind and transfer two molecules of NO per tetramer. These findings support the biochemical basis for the association between α-thalassemia and hypertension.

PT365 Is there a biochemical basis for differential thromboembolic risk in atrial fibrillation? Studies with platelet nitric oxide signalling

Global Heart ◽  
2014 ◽  
Vol 9 (1) ◽  
pp. e240-e241
Author(s):  
Nathan E.K. Procter ◽  
Jocasta Ball ◽  
Doan Ngo ◽  
Yuliy Y. Chirkov ◽  
Jeffrey S. Isenberg ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Atrial Fibrillation ◽  
Biochemical Basis ◽  
Thromboembolic Risk

scholarly journals A Novel Biflavonyloxymethane from Pongamia Pinnata and its Radical Quenching Activity

2011 ◽  
Vol 6 (5) ◽  
pp. 1934578X1100600 ◽  
Author(s):  
Anindita Ghosh ◽  
Suvra Mandal ◽  
Avijit Banerji ◽  
Manoj Kar ◽  
Kalyan Hazra ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
2D Nmr ◽  
Pongamia Pinnata ◽  
Spectral Studies ◽  
Root Bark

The root bark of Pongamia pinnata Pierre (syn P. glabra Vent.) has afforded a new biflavonyloxymethane, pongabiflavone, along with a known furanoflavone, 3-methoxy-(7, 8, 2″, 3″) furanoflavone. The structure of this new compound was elucidated from extensive spectral studies, including 2D-NMR spectroscopic experiments. The antioxidant, radical quenching activity- superoxide and nitric oxide quenching activities of both pongabiflavone and previously isolated karanjabiflavone have been evaluated which can be a key to cure Psoriasis.

scholarly journals Nitric oxide is a mediator of the decrease in cytochrome P450-dependent metabolism caused by immunostimulants

1993 ◽  
Vol 90 (23) ◽  
pp. 11147-11151 ◽  
Author(s):  
O G Khatsenko ◽  
S S Gross ◽  
A B Rifkind ◽  
J R Vane
Keyword(s):  
Nitric Oxide ◽  
Cytochrome P450 ◽  
Nitric Oxide Synthase ◽  
Cytochromes P450 ◽  
Hepatic Metabolism ◽  
Spectral Studies ◽  
Rat Liver Microsomes ◽  
Hepatic Microsomes ◽  
Oxide Synthase

Bacterial lipopolysaccharide (LPS) and a diverse array of other immunostimulants and cytokines suppress the metabolism of endogenous and exogenous substances by reducing activity of the hepatic cytochrome P450 mixed-function oxidase system. Although this effect of immunostimulants was first described almost 40 yr ago, the mechanism is obscure. Immunostimulants are now known to cause NO overproduction by cells via induction of nitric oxide synthase. We have investigated whether NO overproduction is involved in suppressing hepatic metabolism by LPS. In vitro treatment of hepatic microsomes with NO, produced by chemical decomposition of 3-morpholinosydnonimine or by nitric oxide synthase, substantially suppressed cytochrome P450-dependent oxygenation reactions. This effect of NO was seen with hepatic microsomes prepared from two species (rat and chicken) and after exposure to chemicals that induce distinct molecular isoforms of cytochromes P450 (beta-naphthoflavone, 3-methylcholanthrene, and phenobarbital). Spectral studies indicate that NO reacts in vitro with both Fe(2+)- and Fe(3+)-hemes in microsomal cytochromes P450. In vivo, LPS diminished the phenobarbital-induced dealkylation of 7-pentoxyresorufin by rat liver microsomes and reduced the apparent P450 content as measured by CO binding. These LPS effects were associated with induction of NO synthesis; LPS-induced NO synthesis showed a strong positive correlation with the severity of cytochrome P450 inhibition. The decrease in both hepatic microsomal P450 activity and CO binding caused by LPS was largely prevented by the selective NO synthase inhibitor N omega-nitro-L-arginine methyl ester. Our findings implicate NO over-production as a major factor mediating the suppression of hepatic metabolism by immunostimulants such as LPS.

scholarly journals Gastroprotective Effect of Juanislamin on Ethanol-Induced Gastric Lesions in Rats: Role of Prostaglandins, Nitric Oxide and Sulfhydryl Groups in the Mechanism of Action

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2246
Author(s):  
María Elena Sánchez-Mendoza ◽  
Yaraset López-Lorenzo ◽  
Leticia Cruz-Antonio ◽  
Arturo Cruz-Oseguera ◽  
Jazmín García-Machorro ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mechanism Of Action ◽  
Gastrointestinal Disorder ◽  
Sulfhydryl Groups ◽  
Dependent Manner ◽  
Gastric Lesions ◽  
Reference Drug ◽  
Ulcer Disease ◽  
Gastroprotective Effect

Peptic ulcer disease, the most common gastrointestinal disorder, is currently treated with several types of drugs, but all have severe side effects. The aim of the present study was to evaluate the gastroprotective activity of juanislamin, isolated from Calea urticifolia, in a rat model of ethanol-induced gastric lesions. Thirty minutes after orally administering a given dose of juanislamin (from 1 to 30 mg/kg) or carbenoxolone (the reference drug, at 1–100 mg/kg) to rats, 1 mL of ethanol was applied, and the animals were sacrificed 2 h later. The stomachs were removed and opened to measure the total area of lesions in each. To examine the possible participation of prostaglandins, nitric oxide and/or sulfhydryl groups in the mechanism of action of juanislamin, the rats received indomethacin, NG-Nitro-l-arginine methyl ester hydrochloride (l-NAME) or N-ethylmaleimide pretreatment, respectively, before being given juanislamin and undergoing the rest of the methodology. Juanislamin inhibited gastric lesions produced by ethanol in a non-dose-dependent manner, showing the maximum gastroprotective effect (100%) at 10 mg/kg. The activity of juanislamin was not modified by pretreatment with indomethacin, l-NAME or N-ethylmaleimide. In conclusion, juanislamin protected the gastric mucosa from ethanol-induced damage, and its mechanism of action apparently does not involve prostaglandins, nitric oxide or sulfhydryl groups.

Peroxynitrite inhibits amiloride-sensitive Na+ currents inXenopus oocytes expressing αβγ-rENaC

1998 ◽  
Vol 274 (5) ◽  
pp. C1417-C1423 ◽  
Author(s):  
M. D. DuVall ◽  
S. Zhu ◽  
C. M. Fuller ◽  
S. Matalon
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Sulfhydryl Groups ◽  
Channel Activity ◽  
Protein Nitration ◽  
No Donor ◽  
Whole Cell ◽  
Na Currents

We examined the effect of peroxynitrite (ONOO−) on the cloned rat epithelial Na+ channel (αβγ-rENaC) expressed in Xenopusoocytes. 3-Morpholinosydnonimine (SIN-1) was used to concurrently generate nitric oxide (⋅ NO) and superoxide ([Formula: see text] ⋅), which react to form ONOO−, a species known to promote protein nitration and oxidation. Under control conditions, oocytes displayed an amiloride-sensitive whole cell conductance of 7.4 ± 2.8 (SE) μS. When incubated at 18°C with SIN-1 (1 mM) for 2 h (final ONOO− concentration = 10 μM), the amiloride-sensitive conductance was reduced to 0.8 ± 0.5 μS. To evaluate whether the observed inhibition was due to ONOO−, as opposed to ⋅ NO, we also exposed oocytes to SIN-1 in the presence of urate (500 μM), a scavenger of ONOO− and superoxide dismutase, which scavenges[Formula: see text] ⋅, converting SIN-1 from an ONOO− to an ⋅ NO donor. Under these conditions, conductance values remained at control levels following SIN-1 treatment. Tetranitromethane, an agent that oxidizes sulfhydryl groups at pH 6, also inhibited the amiloride-sensitive conductance. These data suggest that oxidation of critical sulfhydryl groups within rENaC by ONOO− directly inhibits channel activity.

Nitric Oxide Blocks Fast, Slow, and Persistent Na+ Channels in C-Type DRG Neurons by S-Nitrosylation

2002 ◽  
Vol 87 (2) ◽  
pp. 761-775 ◽  
Author(s):  
M. Renganathan ◽  
T. R. Cummins ◽  
S. G. Waxman
Keyword(s):  
Nitric Oxide ◽  
Sulfhydryl Groups ◽  
Drg Neurons ◽  
No Donor ◽  
Channel Inactivation ◽  
Dependent Inactivation ◽  
Sodium Channel Inactivation ◽  
Voltage Dependent ◽  
Current Block ◽  
Dependent Protein

C-type dorsal root ganglion (DRG) neurons express three types of Na+ currents: fast TTX-sensitive, slow TTX-resistant, and persistent TTX-resistant Na+ currents. The nitric oxide (NO) donors papa-NONOate and S-nitroso- N-acetyl-dl-penicillamine inhibit all three types of Na+ currents. The NO scavenger hemoglobin abolished the effects of papa-NONOate on Na+ currents, indicating that NO or NO-related species inhibit these Na+ currents. NO donor inhibition of all three types of Na+ currents was reversed by washout. Incubation of neurons with 8-bromo cGMP, a membrane-permeable analogue of cGMP, and cG-PKI, an inhibitor of cGMP-dependent protein kinase, had no effect on papa-NONOate-mediated Na+ current block, demonstrating that Na+ current inhibition is independent of cGMP. Alkylation of free thiols with N-ethylmaleimide prevented the actions of papa-NONOate, suggesting that NO, or a related reactive nitrogen species, modifies sulfhydryl groups on Na+ channels or a closely associated protein. Papa-NONOate-mediated block of Na+ currents is not due to a hyperpolarizing shift in steady state voltage-dependent inactivation. The absence of NO-mediated enhancement of slow inactivation in fast and slow Na+ channels indicates that NO does not inhibit fast and slow Na+ channels by facilitating the transition to a slow inactivated state. These results demonstrate that inhibition of Na+ currents is not due to the modulation of fast and slow sodium channel inactivation. Taken together, these results show that NO or NO-related products modify the sulfhydryl groups on Na+ channels and inhibit Na+ currents by blocking the channel conductance.

N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs

1994 ◽  
Vol 267 (3) ◽  
pp. R767-R772 ◽  
Author(s):  
F. J. Ruiz ◽  
M. G. Salom ◽  
A. C. Ingles ◽  
T. Quesada ◽  
E. Vicente ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Sulfhydryl Groups ◽  
Vascular Effects ◽  
Converting Enzyme Inhibitors ◽  
Depressor Response ◽  
Antihypertensive Response

Recently, in vivo and in vitro studies have implicated nitric oxide as a mediator of the vascular effects of angiotensin-converting enzyme inhibitors (ACEIs). In the present study we hypothesized that N-acetyl-L-cysteine (NAC), by increasing the availability of reduced sulfhydryl groups, would enhance the antihypertensive response to the ACEIs captopril and enalaprilat by a mechanism dependent on nitric oxide. The experiments were performed on instrumented, indomethacin-pretreated, awake spontaneously hypertensive rats (SHRs). Thirty minutes after a bolus of captopril (10 mg/kg iv) was administered, blood pressure decreased from 167 +/- 5 to 147 +/- 6 mmHg (n = 8). The pretreatment with the donor of thiol groups NAC (300 mg/kg iv) potentiated the depressor response to captopril because blood pressure decreased from 172 +/- 3 to 139 +/- 4 mmHg (n = 6). At the dose of 60 micrograms/kg iv, the ACEI enalaprilat did not acutely modify the blood pressure of SHRs (from 172 +/- 5 to 167 +/- 4 mmHg; n = 6). However, when the SHRs were pretreated with NAC, the same dose of enalaprilat significantly reduced blood pressure from 176 +/- 5 to 151 +/- 5 mmHg (n = 6). This potentiation of the depressor response to ACEIs, due to NAC, was not observed when SHRs were pretreated with the nitric oxide inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 50 micrograms.kg-1.min-1 iv). The results of this study suggest that NAC, a donor of sulfhydryl groups, potentiates the antihypertensive response to captopril and enalaprilat in SHR by a nitric oxide-dependent mechanism.

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