scholarly journals Nitric oxide-dependent CYP2B degradation is potentiated by a cytokine-regulated pathway and utilizes the immunoproteasome subunit LMP2

2012 ◽  
Vol 445 (3) ◽  
pp. 377-382 ◽  
Author(s):  
Haiyan Sun ◽  
Choon-myung Lee ◽  
Shweta Tripathi ◽  
Kyung-Bo Kim ◽  
Edward T. Morgan
Keyword(s):  
Nitric Oxide ◽  
Cytochrome P450 ◽  
Protein Degradation ◽  
Rat Hepatocytes ◽  
No Synthase ◽  
Proteolytic Degradation ◽  
Independent Action ◽  
Cytochrome P450 Enzymes ◽  
No Donor ◽  
Synthase Inhibitor

CYP2B proteins in rat hepatocytes undergo NO-dependent proteolytic degradation, but the mechanisms and the reasons for the specificity towards only certain P450 (cytochrome P450) enzymes are yet unknown. In the present study we found that down-regulation of CYP2B proteins by the NO donor NOC-18 is accelerated by pretreatment of the hepatocytes with IL-1 (interleukin-1β) in the presence of an NO synthase inhibitor, suggesting that an NO-independent action of IL-1 contributes to the lability of CYP2B proteins. The immunoproteasome subunit LMP2 (large multifunctional peptidase 2) was significantly expressed in hepatocytes under basal conditions, and IL-1 induced LMP2 within 6–12 h of treatment. CYP2B protein degradation in response to IL-1 was attenuated by the selective LMP2 inhibitor UK-101, but not by the LMP7 inhibitor IPSI. The results show that LMP2 contributes to the NO-dependent degradation of CYP2B proteins, and suggest that induction of LMP2 may be involved in the potentiation of this degradation by IL-1.

Is nitric oxide the final mediator regulating the migrating myoelectric complex cycle?

1995 ◽  
Vol 268 (2) ◽  
pp. G207-G214 ◽  
Author(s):  
A. Rodriguez-Membrilla ◽  
V. Martinez ◽  
M. Jimenez ◽  
E. Gonalons ◽  
P. Vergara
Keyword(s):  
Nitric Oxide ◽  
Small Intestine ◽  
Motor Pattern ◽  
No Synthase ◽  
Phase Iii ◽  
Motor Patterns ◽  
No Donor ◽  
Postprandial State ◽  
Synthase Inhibitor

The main objective was to study the role of nitric oxide (NO) in the conversion of migrating myoelectric complexes (MMC) to the irregular electrical activity characteristic of the postprandial state. Both rats and chickens were implanted with electrodes for electromyography in the small intestine. Intravenous infusion of NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, induced an organized MMC-like pattern in fed rats. Infusion of sodium nitroprusside, a NO donor, disrupted the MMC, inducing a postprandial-like motor pattern in fasting rats. Similarly, in chickens L-NNA mimicked the fasting pattern, consisting of a shortening of phase II, enlargement of phase III, orad displacement of the origin of the MMC, and an increase in the speed of phase III propagation. An inhibition of NO synthesis seems to be involved in the induction of the fasting motor pattern, whereas an increase of NO mediates the occurrence of the fed pattern. It is suggested that NO might be the final mediator in the control of small intestine motor patterns.

scholarly journals Nitric oxide inhibits basolateral 10-pS Cl− channels through the cGMP/PKG signaling pathway in the thick ascending limb of C57BL/6 mice

2016 ◽  
Vol 310 (8) ◽  
pp. F755-F762 ◽  
Author(s):  
Peng Wu ◽  
Zhongxiuzi Gao ◽  
Shiwei Ye ◽  
Zhi Qi
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylyl Cyclase ◽  
Inhibitory Effect ◽  
No Synthase ◽  
Thick Ascending Limb ◽  
Channel Activity ◽  
No Donor ◽  
Cgmp Analog ◽  
Synthase Inhibitor

We used patch-clamp techniques to examine whether nitric oxide (NO) decreases NaCl reabsorption by suppressing basolateral 10-pS Cl− channels in the thick ascending limb (TAL). Both the NO synthase substrate l-arginine (l-Arg) and the NO donor S-nitroso- N-acetylpenicillamine significantly inhibited 10-pS Cl− channel activity in the TAL. The inhibitory effect of l-Arg on Cl− channels was completely abolished in the presence of the NO synthase inhibitor or NO scavenger. Moreover, inhibition of soluble guanylyl cyclase abrogated the effect of l-Arg on Cl− channels, whereas the cGMP analog 8-bromo-cGMP (8-BrcGMP) mimicked the effect of l-Arg and significantly decreased 10-pS Cl− channel activity, indicating that NO inhibits basolateral Cl− channels by increasing cGMP production. Furthermore, treatment of the TAL with a PKG inhibitor blocked the effect of l-Arg and 8-BrcGMP on Cl− channels, respectively. In contrast, a phosphodiesterase 2 inhibitor had no significant effect on l-Arg or 8-BrcGMP-induced inhibition of Cl− channels. Therefore, we conclude that NO decreases basolateral 10-pS Cl− channel activity through a cGMP-dependent PKG pathway, which may contribute to the natriuretic and diuretic effects of NO in vivo.

Effect of nitric oxide on renin secretion. II. Studies in the perfused juxtaglomerular apparatus

1995 ◽  
Vol 268 (5) ◽  
pp. F953-F959 ◽  
Author(s):  
X. R. He ◽  
S. G. Greenberg ◽  
J. P. Briggs ◽  
J. B. Schnermann
Keyword(s):  
Nitric Oxide ◽  
Concentration Ratio ◽  
Juxtaglomerular Apparatus ◽  
No Synthase ◽  
Renin Secretion ◽  
Progressive Decrease ◽  
No Donor ◽  
Concentration Step ◽  
Synthase Inhibitor

To examine the possible role of NO in macula densa control of renin secretion, we examined the effects of varying NO availability on renin release in the isolated perfused rabbit juxtaglomerular apparatus (JGA). Gradual increments of luminal Na/Cl concentration ratio (mM/mM) from 26/7 over 46/27, 66/47, to 86/67 caused a progressive decrease in renin secretion from (as log of nano-Goldblatt hog units vs. time, i.e., log nGU/min) 1.09 +/- 0.34 to 0.46 +/- 0.24 log nGU/min, with the greatest change occurring at the first concentration step. The presence of 0.7 mM N omega-nitro-L-arginine (NNA), an NO synthase inhibitor, in the luminal fluid significantly reduced renin secretion at the lowest Na/Cl concentration ratio to 0.65 +/- 0.32 log nGU/min (P < 0.01 compared with control). Renin secretion at the higher Na/Cl concentration ratios was not significantly affected by NNA compared with control. In contrast to these results, the addition of the NO donor nitroprusside (1 mM) to the bath caused a reduction in renin secretion from 1.0 +/- 0.39 to 0.47 +/- 0.46 log nGU/min (P < 0.05), an effect that was reversed by bath addition of 0.01 mM methylene blue. Similarly, addition of L-arginine (0.7 mM) to the bath reduced renin secretion from 0.99 +/- 0.37 to 0.81 +/- 0.38 log nGU/min (P < 0.01), whereas addition of L-arginine to the luminal fluid increased renin secretion from 0.85 +/- 0.43 to 1.94 +/- 0.46 log nGU/min (P < 0.05). The stimulatory effect of luminal L-arginine was reversed by the luminal addition of NNA.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Nitric Oxide Ameliorates Plant Metal Toxicity by Increasing Antioxidant Capacity and Reducing Pb and Cd Translocation

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1981
Author(s):  
Abolghassem Emamverdian ◽  
Yulong Ding ◽  
James Barker ◽  
Farzad Mokhberdoran ◽  
Muthusamy Ramakrishnan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Heavy Metal ◽  
Sodium Nitroprusside ◽  
Metal Toxicity ◽  
Heavy Metal Toxicity ◽  
No Synthase ◽  
Bamboo Species ◽  
No Donor ◽  
Cd Toxicity ◽  
Synthase Inhibitor

Recently, nitric oxide (NO) has been reported to increase plant resistance to heavy metal stress. In this regard, an in vitro tissue culture experiment was conducted to evaluate the role of the NO donor sodium nitroprusside (SNP) in the alleviation of heavy metal toxicity in a bamboo species (Arundinaria pygmaea) under lead (Pb) and cadmium (Cd) toxicity. The treatment included 200 µmol of heavy metals (Pb and Cd) alone and in combination with 200 µM SNP: NO donor, 0.1% Hb, bovine hemoglobin (NO scavenger), and 50 µM L-NAME, N(G)-nitro-L-arginine methyl ester (NO synthase inhibitor) in four replications in comparison to controls. The results demonstrated that the addition of L-NAME and Hb as an NO synthase inhibitor and NO scavenger significantly increased oxidative stress and injured the cell membrane of the bamboo species. The addition of sodium nitroprusside (SNP) for NO synthesis increased antioxidant activity, protein content, photosynthetic properties, plant biomass, and plant growth under heavy metal (Pb and Cd) toxicity. It was concluded that NO can increase plant tolerance for metal toxicity with some key mechanisms, such as increasing antioxidant activities, limiting metal translocation from roots to shoots, and diminishing metal accumulation in the roots, shoots, and stems of bamboo species under heavy metal toxicity (Pb and Cd).

Regulation of VIP release from rat enteric nerve terminals: evidence for a stimulatory effect of NO

1996 ◽  
Vol 271 (4) ◽  
pp. G568-G574 ◽  
Author(s):  
H. D. Allescher ◽  
M. Kurjak ◽  
A. Huber ◽  
P. Trudrung ◽  
V. Schusdziarra
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Nerve Terminals ◽  
No Donor ◽  
Cyclic Monophosphate ◽  
A 23187 ◽  
Basal Release ◽  
Significant Release ◽  
Synthase Inhibitor ◽  
Stimulation Of

The basal release of vasoactive intestinal polypeptide (VIP) from freshly prepared enriched synaptosomes was 159.1 +/- 17.3 fmol/mg protein (100%), which constituted 2.5% of the total VIP content. Basal VIP release was reduced by 65% by removal of external Ca2+. Release of VIP was stimulated by depolarization with KCl (65 mM, 143%) and in the presence of veratridine (10(-6) M, 184%), monensin (10(-5) M, 131%), and the Ca2+ ionophore A-23187 (10(-6) M, 160%). Stimulation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent mechanisms using isoproterenol (10(-6)-10(-4) M) and forskolin (10(-6) and 10(-5) M) had no stimulatory influence on VIP release. In contrast, sodium nitroprusside (10(-4) M, 198%), the nitric oxide (NO) donor 3-(morpholino)sydnonimine (10(-4) M, 155%), and the guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-bromo cGMP (10(-4) M, 196%) caused a significant release of VIP. L-Arginine (10(-3) M, 246%) also caused a significant increase of VIP release that was antagonized by the NO synthase inhibitor N omega-nitro-L-arginine methyl ester (5 x 10(-4) M, 131%), which had no effect when given alone. The results demonstrate that VIP can be released from enriched synaptosomes by Ca(2+)-dependent mechanisms by NO agonists or NO-dependent mechanisms. It is speculated that this VIP release is induced by a presynaptic stimulatory mechanism of NO and this effect could enhance or contribute to the action of NO.

Rapid tachyphylaxis to hemodynamic effects of PACAP-27 after inhibition of nitric oxide synthesis

1999 ◽  
Vol 276 (6) ◽  
pp. H2117-H2126 ◽  
Author(s):  
Erin J. Whalen ◽  
Mark D. Travis ◽  
Alan Kim Johnson ◽  
Stephen J. Lewis
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Receptor Agonist ◽  
No Synthase ◽  
Nitric Oxide Synthesis ◽  
No Donor ◽  
Pituitary Adenylate Cyclase ◽  
Cgmp Analog ◽  
Synthase Inhibitor

The vasodilator effects of pituitary adenylate cyclase-activating polypeptide (PACAP)-27 are subject to tachyphylaxis in rats treated with the nitric oxide (NO) synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME). We examined whether this tachyphylaxis could be prevented by administration of the putative endothelium-derived nitrosyl factor S-nitroso-l-cysteine (l-SNC) and whetherl-SNC may exert its effects via increases in cGMP levels in vascular smooth muscle. Five doses of PACAP-27 (2 nmol/kg iv) produced pronounced vasodilator responses in saline-treated rats. These responses were not subject to tachyphylaxis. The first injection of PACAP-27 (2 nmol/kg iv) inl-NAME-treated (50 μmol/kg iv) rats produced vasodilator responses similar to those in saline-treated rats, whereas subsequent injections produced progressively smaller responses. The injection ofl-SNC (1,200 nmol/kg iv) before each injection of PACAP-27 prevented tachyphylaxis to the Gs protein-coupled receptor agonist in l-NAME-treated rats, whereas equihypotensive doses of the NO donor sodium nitroprusside (100 μg/kg iv) did not. The injection of the membrane-permeant cGMP analog 8-(4-chlorophenylthio)guanosine 3′,5′-cyclic monophosphate (8-CPT-cGMP; 30 μmol/kg iv) tol-NAME-treated rats restored resting hemodynamic values to pre-l-NAME levels but did not prevent the development of tachyphylaxis to PACAP-27. These results suggest that nitrosyl factors prevent the development of tachyphylaxis to the hemodynamic actions of PACAP-27. These nitrosyl factors may act independently of their ability to generate cGMP in vascular smooth muscle.

Permissive role for nitric oxide in active thermoregulatory vasodilation in rabbit ear

1995 ◽  
Vol 269 (5) ◽  
pp. H1613-H1618 ◽  
Author(s):  
D. M. Farrell ◽  
V. S. Bishop
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Whole Body ◽  
Lingual Artery ◽  
No Donor ◽  
Rabbit Ear ◽  
Group 2 ◽  
Synthase Inhibitor ◽  
Permissive Role ◽  
Group 1

The present study was designed to test the hypothesis that during whole body heating (WBH), nitric oxide (NO) synthesized in the endothelium acts synergistically with an unknown neurotransmitter to elicit active vasodilation. Rabbits were instrumented for the measurement of mean arterial pressure, heart rate, and ear blood flow (EBF) (Doppler ultrasound). During WBH, either N omega-nitro-L-arginine methyl ester (L-NAME, 10-40 mg over 10-15 min, n = 6 rabbits; group 1), a NO synthase inhibitor, or saponin (30-40 mg over 10-20 min, n = 6 rabbits; group 2), a detergent that denudes the endothelium, was given via a lingual artery catheter until thermoregulatory vasodilation was reversed. When EBF stabilized at the new reduced level, the NO donor, sodium nitroprusside (SNP), was infused (0.2-1.0 mg/ml, 0.01-0.05 ml/min, 2-5 min) via the lingual artery catheter. During WBH, EBF increased from 0.39 +/- 0.08 to 6.47 +/- 0.63 kHz in group 1, and from 0.69 +/- 0.18 to 5.72 +/- 0.49 kHz in group 2. Infusion of L-NAME decreased EBF in group 1 to 1.97 +/- 0.40 kHz. Infusion of saponin decreased EBF in group 2 to 1.23 +/- 0.40 kHz. Subsequent SNP infusion during hyperthermia returned EBF to 6.88 +/- 0.72 kHz in group 1 and 5.53 +/- 1.27 kHz in group 2 but had no effect when administered during normothermia. These results suggest that NO acts in conjunction with another substance, presumably the neurotransmitter released on WBH, to elicit thermoregulatory vasodilation.

Nitric oxide does not modulate whole body oxygen consumption in anesthetized dogs

1999 ◽  
Vol 86 (6) ◽  
pp. 1944-1949 ◽  
Author(s):  
George J. Crystal ◽  
Xiping Zhou ◽  
Ayman A. Halim ◽  
Syed Alam ◽  
Mohammad El-Orbany ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Critical Level ◽  
No Synthase ◽  
Whole Body ◽  
No Production ◽  
No Donor ◽  
Standard Methods ◽  
Vasodilator Effect ◽  
Anesthetized Dogs ◽  
Synthase Inhibitor

The effects of the NO synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME) and the NO donor sodium nitroprusside (SNP) on whole body O2 consumption (V˙o 2) were assessed in 16 dogs anesthetized with fentanyl or isoflurane. Cardiac output (CO) and mean arterial pressure (MAP) were measured with standard methods and were used to calculate V˙o 2and systemic vascular resistance (SVR). Data were obtained in each dog under the following conditions: 1) Control 1, 2) SNP (30 μg ⋅ kg−1 ⋅ min−1iv) 3) Control 2, 4)l-NAME (10 mg/kg iv), and 5) SNP and adenosine (30 and 600 μg ⋅ kg−1 ⋅ min−1iv, respectively) after l-NAME. SNP reduced MAP by 29 ± 3% and SVR by 47 ± 3%, while it increased CO by 39 ± 9%.l-NAME had opposite effects; it increased MAP and SVR by 24 ± 4% and 103 ± 11%, respectively, and it decreased CO by 37 ± 3%. Neither agent changedV˙o 2 from the baseline value of 4.3 ± 0.2 ml ⋅ min−1 ⋅ kg−1, since the changes in CO were offset by changes in the arteriovenous O2 difference. Both SNP and adenosine returned CO to pre-l-NAME values, butV˙o 2 was unaffected. We conclude that 1) basally released endogenous NO had a tonic systemic vasodilator effect, but it had no influence on V˙o 2; 2) SNP did not alterV˙o 2 before or after inhibition of endogenous NO production; 3) the inability ofl-NAME to increaseV˙o 2 was not because CO, i.e., O2 supply, was reduced below the critical level.

Nitric oxide modulates endotoxin-induced platelet-endothelial cell adhesion in intestinal venules

2002 ◽  
Vol 282 (3) ◽  
pp. H1111-H1117 ◽  
Author(s):  
Wolfgang H. Cerwinka ◽  
Dianne Cooper ◽  
Christian F. Krieglstein ◽  
Martin Feelisch ◽  
D. Neil Granger
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Soluble Guanylate Cyclase ◽  
Vascular Diseases ◽  
Fold Increase ◽  
No Synthase ◽  
No Donor ◽  
Platelet Endothelial Cell Adhesion ◽  
Adhesive Interactions ◽  
Synthase Inhibitor

Although platelets have been implicated in the pathogenesis of vascular diseases, little is known about factors that regulate interactions between platelets and the vessel wall under physiological conditions. The objectives of this study were to 1) define the contribution of nitric oxide (NO) to endotoxin (lipopolysaccharide, LPS)-induced platelet-endothelial cell (P/E) adhesion in murine intestinal venules and 2) determine whether the antiadhesive action of NO is mediated by soluble guanylate cyclase (sGC). Adhesive interactions between platelets and endothelial cells were monitored by intravital microscopy. LPS administration into control wild-type mice (WT) resulted in a >15-fold increase in P/E adhesion. Similar responses were observed using endothelial NO synthase (eNOS)-deficient platelets. However, treatment with the NO donor diethylenetriamine-nitric oxide (DETA-NO) attenuated the P/E adhesion response to LPS, whereas the NO synthase inhibitor NG-nitro-l-arginine methyl ester or eNOS deficiency resulted in an exacerbation. P/E adhesion response did not differ between LPS-treated WT and inducible NOS-deficient mice. Inhibition of sGC abolished the attenuating effects of DETA-NO, whereas the sGC activator 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1) reduced LPS-induced P/E adhesion. These findings indicate that 1) eNOS-derived NO attenuates endotoxin-induced P/E adhesion and 2) sGC is responsible for the antiadhesive action of NO.

Sign in / Sign up

Export Citation Format

Share Document