Increased nitric oxide production in platelets from severe chronic renal failure patients

2011 ◽  
Vol 89 (2) ◽  
pp. 97-102 ◽  
Author(s):  
Mariana Alves de Sá Siqueira ◽  
Tatiana M.C. Brunini ◽  
Natália Rodrigues Pereira ◽  
Marcela Anjos Martins ◽  
Monique Bandeira Moss ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Chronic Renal Failure ◽  
Platelet Aggregation ◽  
Plasma Levels ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
No Production ◽  
Dialysis Treatment ◽  
Cgmp Pathway

Nitric oxide (NO) production occurs through oxidation of the amino acid l-arginine by NO synthase (NOS). NO inhibits platelet activation by increasing the levels of cyclic guanosine monophosphate (cGMP), thus maintaining vascular homeostasis. Our group previously demonstrated ( da Silva et al. 2005 ) an enhancement of the l-arginine–NO–cGMP pathway in platelets taken from chronic renal failure (CRF) patients on haemodialysis associated with reduced platelet aggregation. We investigate the platelet l-arginine–NO–cGMP pathway, platelet function, and inflammation from patients in CRF on conservative treatment. A total of 42 CRF patients and 42 controls (creatinine clearance = 27 ± 3 vs. 93 ± 1 mL per min per 1.73 m2, respectively) participated in this study. NOS activity and expression and cGMP concentration were measured in platelets. Platelet aggregation induced by collagen or ADP was evaluated and plasma levels of fibrinogen were determined by the Clauss method. A marked increase in basal NOS activity was seen in undialysed CRF patients compared with controls, accompanied by an elevation of fibrinogen plasma levels. There were no differences in expression of NOS and in cGMP levels. In this context, platelet aggregation was not affected. We provide the first evidence of increased intraplatelet NO biosynthesis in undialysed CRF patients, which can be an early marker of future haemostatic abnormalities during dialysis treatment.

scholarly journals L-Arginine Supplementation in Type II Diabetic Rats Preserves Renal Function and Improves Insulin Sensitivity by Altering the Nitric Oxide Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Taylor Claybaugh ◽  
Sarah Decker ◽  
Kelly McCall ◽  
Yuriy Slyvka ◽  
Jerrod Steimle ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Renal Dysfunction ◽  
Cell Damage ◽  
Cyclic Guanosine Monophosphate ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Rats ◽  
Guanosine Monophosphate ◽  
No Production ◽  
Type Ii

Rat studies demonstrated that type II diabetes mellitus (T2DM) decreases both the production and bioavailability of nitric oxide (NO). L-arginine (LA) provides the precursor for the production of NO. We hypothesized that LA dietary supplementation will preserve NO production via endothelial nitric oxide synthase (eNOS) causing renal microvascular vasodilation and increased glomerular blood flow and thus increasing glomerular filtration rate (GFR). This would impede the formation of reactive oxygen species which contributes to cell damage and death. LA supplementation preserved GFR in the treated diabetic rats compared to untreated diabetic rats. We provide evidence that this effect may be due to increased levels of eNOS and urinary cyclic guanosine monophosphate, which leads to renal microvascular vasodilation. Plasma nitrotyrosine was decreased in the LA treated rats; however, plasma nitrite levels remained unaffected as expected. Marked improvements in glucose tolerance were also observed in the LA treated diabetic rats. These results demonstrate that LA supplementation preserves NO activity and may delay the onset of insulin resistance and renal dysfunction during hyperglycemic stress. These results suggest the importance of the NO pathway in consequent renal dysfunction and in the development of insulin resistance in diabetic rats.

EFFECTS OF HAEMODIALYSIS AND CONTINUOUS AMBULATORY PERITONEAL DIALYSIS ON NITRIC OXIDE SERUM CONCENTRATION IN PATIENTS WITH CHRONIC RENAL FAILURE

2008 ◽  
Vol 37 (2) ◽  
pp. 93-98
Author(s):  
Amela Matavulj ◽  
Pedja Kovacevic ◽  
Jasminko Huskic ◽  
Slavimir Veljkovic ◽  
Zvezdana Rajkovaca ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Failure ◽  
Peritoneal Dialysis ◽  
Chronic Renal Failure ◽  
Serum Concentration ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
No Production ◽  
Bleeding Tendency ◽  
Wide Range ◽  
Hemostatic Disorders

Introduction: Nitric oxide (NO) plays an important role in a wide range of physiologic and pathophysiological processes. A major mediator of endothelial function, NO regulates vasodilatory and antithrombotic actions in the vasculature and plays a role in reproductive functions, bronchodilation, bone formation, memory, insulin sensitivity, and gastrointestinal relaxation. Impaired NO bioactivity is strongly associated with endothelial dysfunction. NO, an L-arginine derivative, also exerts a variety of renal and extrarenal physiological and pathophysiological effects. It seems that NO synthetic pathway could have a key role in mediating the complex hemodynamic and hemostatic disorders associated to the progression of renal disease. It remains unclear whether endogenous NO production is increased or decreased in patients with chronic renal failure. The objective of this study was to present the effect of different dialysis treatment on NO serum concentration in patients with chronic renal failure.Patients and Methods: To evaluate endogenous NO production in these patients we studied plasma NO2 and NO3 levels (determined with the Griess method) in patients who underwent regular continuous ambulatory peritoneal dialysis or repeated haemodialysis and in healthy subjects. The study included 51 patients suffering from chronic renal failure and 30 healthy subjects.Results: Our results show that patients with chronic renal failure had a significantly higher NO serum concentration than controls. These values did not differ between patients on haemodialysis and those on continuous ambulatory peritoneal dialysis. NO serum concentration did not differ between female and male independently of the patient’s treatment.Discussion and Conclusion: From obtained results we can concluded that uremia is associated with excessive systemic NO release independently of the patient’s treatment. Alter (increase) NO synthesis may help to explain some pathological changes seen in uraemia such as bleeding tendency, a well-known complication of uremia and hemodialysis hypotension.

scholarly journals Muscle fiber type differences in nitrate and nitrite storage and nitric oxide signaling in rats

2020 ◽  
Author(s):  
Gary M. Long ◽  
Derrick A. Gray ◽  
Ashley D. Troutman ◽  
Amanda Fisher ◽  
Mary Beth Brown ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fiber Type ◽  
Vastus Lateralis ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Cgmp Level ◽  
No Production ◽  
Nitric Oxide Signaling ◽  
Slow Twitch ◽  
Fast Twitch

AbstractRecent studies have emphasized the importance of the nitric oxide synthase (NOS)-independent, nitrate (NO3−) → nitrite (NO2−) → nitric oxide (NO) pathway in skeletal muscle. In particular, it has been hypothesized that this pathway is especially active in type II, or fast-twitch, muscle fibers, necessitating greater NO3− and NO2− storage. We therefore measured NO3− and NO2− concentrations in the predominantly fast-twitch vastus lateralis and predominantly slow-twitch soleus muscles of rats. Contrary to the above hypothesis, we found that NO3− and NO2− concentrations were 3.4-fold and 1.8-fold higher, respectively, in the soleus. On the other hand, NO signaling (i.e., cyclic guanosine monophosphate (cGMP) level) was comparable in the two muscles. Although the physiological significance of these observations remains to be determined, we speculate that NO production via the NO3− → NO2− → NO pathway is normally higher in slow-twitch muscles, thus helping compensate for their inherently lower NOS activity.

Effect of nitric oxide on the cyclic guanosine monophosphate (cGMP) pathway during meiosis resumption in bovine oocytes

2014 ◽  
Vol 81 (4) ◽  
pp. 556-564 ◽  
Author(s):  
Kátia R. Lancellotti Schwarz ◽  
Pedro R. Lisboa Pires ◽  
Ligia Garcia Mesquita ◽  
Marcos R. Chiaratti ◽  
Cláudia Lima Verde Leal
Keyword(s):  
Nitric Oxide ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Cgmp Pathway ◽  
Bovine Oocytes

Volatile Anesthetics Do Not Alter Bradykinin-induced Release of Nitric Oxide or L-Citrulline in Crystalloid Perfused Guinea Pig Hearts 

1998 ◽  
Vol 89 (2) ◽  
pp. 421-433 ◽  
Author(s):  
Satoshi Fujita ◽  
David L. Roerig ◽  
Wynda W. Chung ◽  
Zeljko J. Bosnjak ◽  
David F. Stowe
Keyword(s):  
Nitric Oxide ◽  
Guinea Pig ◽  
Volatile Anesthetics ◽  
Left Ventricular ◽  
Guanosine Monophosphate ◽  
No Production ◽  
Permeable Membrane ◽  
No Release ◽  
Cgmp Pathway ◽  
Perfused Hearts

Background Nitric oxide (NO) and L-citrulline (L-cit) are released by endothelial NO synthase (eNOS) to induce vasodilation via guanylyl cyclase and cyclic guanosine monophosphate (cGMP). Volatile anesthetics directly reduce vascular muscle tone, but their effects on the eNOS cGMP pathway is controversial. The aim of this study was to examine the effects of anesthetics on bradykinin-induced increases in flow, NO, and L-cit in isolated hearts. Methods Guinea pig hearts were isolated, perfused at 55 mmHg with a crystalloid or erythrocyte perfusate at 37 degrees C, and heart rate, left ventricular pressure, coronary flow (CF), effluent pH, and oxygen tension were monitored. Effluent [NO] was measured by a Clark-type electrode (sensitivity > or = 1 nM = 3 pA) with a selectively permeable membrane. Effluent [L-cit] was measured by chromatography. Before, during, and after exposure to halothane, isoflurane, or sevoflurane, hearts were infused with as much as 100 nM bradykinin to induce increases in CF and effluent release of NO and L-cit. Results In crystalloid-perfused hearts, 10 nm bradykinin produced maximal concentration-dependent increases in CF (87+/-2%), [NO] (24+/-4 nM), NO release (128+/-18 pmol x g(-1) x min(-1)), and [L-cit] (58+/-8 nM). Isoflurane slightly increased CF but not NO. Anesthetics did not alter the bradykinin-induced CF, NO slope relationship, or change [L-cit]. In erythrocyte-perfused hearts, isoflurane also did not alter the bradykinin-induced increase in CF and decrease in percentage of oxygen extracted. Conclusions This is the first study to simultaneously measure CF with bradykinin-induced changes in [NO] and [L-cit] in the presence of halothane, isoflurane, and sevoflurane in intact hearts. The study shows for the first time that volatile anesthetics do not alter the CF to NO relationship and suggests that NO production, NO release, and NO vasodilatory effects mediated by the eNOS cGMP pathway are not significantly affected by anesthetics in crystalloid or erythrocyte-perfused guinea pig hearts.

scholarly journals Calcium blood level modulates endogenous nitric oxide action: effects of parathroidectomy in patients with hyperparathyroidism

1998 ◽  
Vol 156 (2) ◽  
pp. 231-235 ◽  
Author(s):  
V Martina ◽  
GA Bruno ◽  
V Brancaleoni ◽  
E Zumpano ◽  
M Tagliabue ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylate Cyclase ◽  
Normal Values ◽  
Normal Subjects ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Blood Levels ◽  
Free Calcium ◽  
No Production ◽  
High Calcium

Platelet cyclic guanosine monophosphate (cGMP) is produced by soluble guanylate cyclase (sGC), the activity of which is modulated by the activity of nitric oxide (NO) constitutive synthase (cNOS) which, in turn, is activated by a calcium/calmodulin complex. In primary hyperparathyroidism (H-PTH) an increase in platelet free calcium levels is present. In this study we evaluate the platelet cGMP levels, as an expression of NO production, in the presence of 3-isobutyl-1-methylxanthine (IBMX) alone (IBMXcGMP) and after stimulation by ionomycine (IONO; IONOcGMP) and sodium nitroprusside (SNP; SNPcGMP), in eight subjects affected by H-PTH before and after removal of adenoma. Platelet cGMP levels were also measured in seven normal subjects. IBMXcGMP and IONOcGMP were elevated in H-PTH patients compared with normal subjects (1.9 +/- 0.3 vs 0.8 +/- 0.2 fmol/10(6) platelets and 2.7 +/- 0.4 vs 1.4 +/- 0.3; P < 0.02 and P < 0.05 respectively) but SNPcGMP was unaffected (3.9 +/- 0.6 vs 2.5 +/- 0.5). After parathyroidectomy, blood levels of intact parathyroid hormone (i-PTH), total calcium (t-Ca), IBMXcGMP and IONOcGMP all decreased (177.5 +/- 23.9 vs 45.0 +/- 8.8 pg/ml, P < 0.005; 6.5 +/- 0.5 vs 4.6 +/- 0.1 mEq/1, P < 0.005; 1.9 +/- 0.3 vs 0.8 +/- 0.2, P < 0.005; 2.7 +/- 0.4 vs 1.8 +/ 0.3, P < 0.05 respectively), while SNPcGMP was not modified (3.9 +/- 0.6 vs 4.3 +/- 0.9). t-Ca and i-PTH were directly correlated with IBMXcGMP (P < 0.02, rs = 0.613; P < 0.02, rs = 0.576 respectively) and i-PTH was also correlated with t-Ca (P < 0.001), rs = 0.840). In conclusion: (1) levels of IBMXcGMP and IONOcGMP are high in subjects with H-PTH; (2) after surgery both IBMXcGMP and IONOcGMP decrease to normal values. As IBMXcGMP expresses basal cGMP and IONOcGMP expresses the cGMP after cNOS stimulation, it can be speculated that the increase in NO production could be a mechanism to downregulate the vasoconstriction which may be caused by the high calcium levels in smooth muscle cells. After surgery, together with the normalization of calcium levels, NO production also returned to normal values.

Inhalational Anesthetic Effects on Rat Cerebellar Nitric Oxide and Cyclic Guanosine Monophosphate Production

1997 ◽  
Vol 86 (3) ◽  
pp. 689-698 ◽  
Author(s):  
Appavoo Rengasamy ◽  
Thomas N. Pajewski ◽  
Roger A. Johns
Keyword(s):  
Nitric Oxide ◽  
Nmda Receptor ◽  
Cyclic Guanosine Monophosphate ◽  
Inhibitory Effect ◽  
No Synthase ◽  
Guanosine Monophosphate ◽  
Excitatory Neurotransmitter ◽  
Cgmp Production ◽  
Inhalational Anesthetics ◽  
Cgmp Pathway

Background Inhalational anesthetics interact with the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway in the central nervous system (CNS) and attenuate excitatory neurotransmitter-induced cGMP concentration. The site of anesthetic action on the NO-cGMP pathway in the CNS remains controversial. This study investigated the effect of inhalational anesthetics on N-methyl-D-aspartate (NMDA)-stimulated NO synthase activity and cyclic cGMP production in rat cerebellum slices. Methods The interaction of inhalational anesthetics with NO synthase activation and cGMP concentration was determined in cerebellum slices of 10-day-old rats. Nitric oxide synthase activity in cerebellum slices was assessed by measuring the conversion of L-[3H]arginine to L-[3H]citrulline. The cGMP content of cerebellum slices was measured by radioimmunoassay. Results Isoflurane at 1.5% and 3% enhanced the NMDA-stimulated NO synthase activity by two times while halothane at 1.5% and 3% produced no significant effect. However, the NMDA-stimulated cGMP production was inhibited by both anesthetic agents. The anesthetic inhibition of cGMP accumulation was not significantly altered by a mixture of superoxide dismutase and catalase or by glycine, a coagonist of the NMDA receptor. Conclusions The enhancement of NMDA-induced NO synthase activity by isoflurane and the inhibition of NMDA-stimulated cGMP production by halothane and isoflurane suggests that inhalational anesthetics interfere with the neuronal NO-cGMP pathway. This inhibitory effect of anesthetics on cGMP accumulation is not due to either their interaction with the glycine binding site of the NMDA receptor or to the action of superoxide anions.

scholarly journals THE ADMINISTRATION OF FISH OIL TO PREGNANT RATS AGAINST THE BACKGROUND OF STRESS PREVENTS THE DISORDERS OF NITRIC OXIDE FORMATION AND ACTION IN OFFSPRING

2021 ◽  
Vol 20 (4) ◽  
pp. 27-37
Author(s):  
A.N. Pauliukevich ◽  
Keyword(s):  
Nitric Oxide ◽  
Fish Oil ◽  
Blood Serum ◽  
Cyclic Guanosine Monophosphate ◽  
Female Offspring ◽  
Guanosine Monophosphate ◽  
Control Fish ◽  
No Production ◽  
Diene Conjugates ◽  
Pregnant Rats

Objectives. To assess the possibility to prevent the disturbances of nitric oxide (NO) formation and action system in prenatally stressed rats with the help of fish oil administered to their mothers during pregnancy against the background of stress. Material and methods. Outbred pregnant rats weighing 180-220 g were divided into equal groups (n=10): «Pregnant control», «Pregnant stress», «Pregnant control + fish oil», «Pregnant stress+fish oil». Stress was reproduced by exposure to stressors on different days of pregnancy: food deprivation during one day, contact with cats’ feces during one day, and immobilization in water (20 minutes, t°=23±2). Rats of the groups «Pregnant control + fish oil» and «Pregnant stress + fish oil» received 0.1 ml of fish oil (Biosola, Lithuania) as a gavage at a daily dose of 60 mg/kg of eicosapentaenoic and docosahexaenoic acids; rats of groups «Pregnant control» and «Pregnant stress» received an equivalent volume of starch solution (0.1 ml). In 3-month-old offspring (n=181), systolic, diastolic, and mean arterial pressure (SBP, DBP, MAP, respectively) were measured noninvasively; the concentration of endothelial and inducible isoforms of NO-synthase (eNOS and iNOS, respectively), cyclic guanosine monophosphate (cGMP), asymmetric dimethylarginine (ADMA) was determined in blood serum by ELISA; the content of nitrates/nitrites (NO<sub>3</sub><sup>-</sup>/NO<sub>2</sub><sup>-</sup>), diene conjugates (DC), malondialdehyde (MDA), superoxide dismutase (SOD) and catalase was determined spectrophotometrically in blood serum. Results. Fish oil which was administered to pregnant rats under stress led to the increase of reduced compared with control males content of eNOS, cGMP, SOD, catalase, NO<sub>3</sub><sup>-</sup>/NO<sub>2</sub><sup>-</sup> (by 10.7%, 48.3%, 62.6%, 31.3%, 91.7%, respectively); the decrease of increased concentration of iNOS, ADMA, DC, MDA (by 21.8%, 37.4%, 61.2%, 75.9%, respectively) in the blood serum of male offspring. In female offspring of group «Pregnant stress + fish oil» the decrease of increased content of iNOS, DC, MDA (by 25.8%, 2.6 and 4.9 times, respectively) with the increase of reduced concentration of NO<sub>3</sub><sup>-</sup>/NO<sub>2</sub><sup>-</sup>, SOD (by 84.6%, 52%, respectively) were determined in the blood serum. The introduction of fish oil to pregnant rats against the background of stress prevented SBP, DBP, and MAP increasing in the offspring. Conclusions. The administration of fish oil to rats during pregnancy under chronic stress prevents the impairment of NO production and action in the offspring.

scholarly journals Shear-induced nitric oxide production by endothelial cells

2016 ◽  
Author(s):  
K. Sriram ◽  
J. G. Laughlin ◽  
P. Rangamani ◽  
D. M. Tartakovsky
Keyword(s):  
Nitric Oxide ◽  
Endothelial Nitric Oxide Synthase ◽  
Calcium Influx ◽  
Cyclic Guanosine Monophosphate ◽  
G Protein Coupled Receptors ◽  
Guanosine Monophosphate ◽  
No Production ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
G Protein Coupled

AbstractWe present a biochemical model of the wall shear stress (WSS)-induced activation of endothelial nitric oxide synthase (eNOS) in an endothelial cell (EC). The model includes three key mechanotransducers: mechanosensing ion channels, integrins and G-protein-coupled receptors. The reaction cascade consists of two interconnected parts. The first is rapid activation of calcium, which results in formation of calcium-calmodulin complexes, followed by recruitment of eNOS from caveolae. The second is phosphoryaltion of eNOS by protein kinases PKC and AKT. The model also includes a negative feedback loop due to inhibition of calcium influx into the cell by cyclic guanosine monophosphate (cGMP). In this feedback, increased nitric oxide (NO) levels cause an increase in cGMP levels, so that cGMP inhibition of calcium influx can limit NO production. The model was used to predict the dynamics of NO production by an EC subjected to a step increase of WSS from zero to a finite physiologically relevant value. Among several experimentally observed features, the model predicts a highly nonlinear, bipha-sic transient behavior of eNOS activation and NO production: a rapid initial activation due to the very rapid influx of calcium into the cytosol (occurring within 1 to 5 minutes) is followed by a sustained period of activation due to protein kinases.AcronymsAKT, protein kinase B; [Ca2+]c, [Ca2+]s, [Ca2+]e and [Ca2+]b, cytosolic, stored, external and buffer concentrations of calcium ions, respectively; Ca3-CaM and Ca4-CaM, calcium-calmodulin complexes with 3 and 4 calcium ions bound to CaM, respectively; CaM, calmodulin; CCE, capacitative calcium entry; cGMP, cyclic guanosine monophosphate; EC, endothelial cell; ECM, extracellular matrix; eNOS, endothelial nitric oxide synthase; eNOScav, eNOS bound to caveolin; eNOS*, eNOS-CaM complex phosphorylated at Ser-1197; eNOS0, caveolin-bound eNOS phosphorylated at Thr-495; ER, endoplasmic reticulum; FAK, focal adhesion kinase; G, active G proteins; Gt, total G proteins; GPCR, G-protein-coupled receptors; Hsp90, heat shock protein 90; GTP, guanosine triphosphate; IP3, inositol triphosphate; L-Arg, L-form of arginine; MSIC, mechanosensing ion channel; NO, nitric oxide; O2, oxygen; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phos-phatidylinositol (3,4,5)-triphosphate; PI3K, phosphatidylinositide 3-kinases; PKC, protein kinase C; RBC, red blood cell; sGC, soluble guanylate cyclase; WSS, wall shear stress

scholarly journals Nitric Oxide Suppresses the Expression of Bcl-2 Binding Protein BNIP3 in Hepatocytes

2001 ◽  
Vol 276 (50) ◽  
pp. 46887-46895 ◽  
Author(s):  
Ruben Zamora ◽  
Louis Alarcon ◽  
Yoram Vodovotz ◽  
Binnie Betten ◽  
Peter K. M. Kim ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cultured Cells ◽  
Binding Protein ◽  
Soluble Guanylyl Cyclase ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate ◽  
Northern Analysis ◽  
No Production ◽  
No Donor ◽  
Factor Α

Nitric oxide (NO) is not only an important signaling molecule, but it also regulates the expression of a number of genes in the liver. We have previously shown that apoptosis in hepatocytes exposed to tumor necrosis factor-α and actinomycin D is prevented by NO derived from the inducible nitric-oxide synthase (iNOS), by mechanisms that are both dependent on and independent of modulation of cyclic guanosine monophosphate (cGMP) subsequent to activation of soluble guanylyl cyclase (sGC). We hypothesize that one mechanism by which NO exerts these effects is by regulating the expression of genes involved in apoptosis. We used differential display-polymerase chain reaction to isolate NO-regulated genes in hepatocytes fromiNOSknockout mice (to eliminate endogenous inducible NO production). Using this analysis, we identified a NO-suppressed gene fragment homologous with the pro-apoptotic Bcl-2 binding protein BNIP3. Northern analysis confirmed the NO-dependent suppression ofBNIP3in cultured cells. Similarly, the NO donorS-nitroso-N-acetyl-dl-penicillamine (1–1000 μm) down-regulated the expression ofBNIP3in bothiNOSknockout and wild-type hepatocytes. This effect of NO was reversed by the sGC inhibitor 1H-(1,2,4)-oxadiazole[4,3-a]quinoxalon-1-one (ODQ),suggesting the involvement of the sGC/cGMP pathway in the modulation of BNIP3 by NO. We propose that suppression of BNIP3 expression is one sGC/cGMP-dependent mechanism by which NO might affect the process of hepatocyte apoptosis.

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