scholarly journals Expression of islet inducible nitric oxide synthase and inhibition of glucose-stimulated insulin release after long-term lipid infusion in the rat is counteracted by PACAP27

2007 ◽  
Vol 292 (5) ◽  
pp. E1447-E1455 ◽  
Author(s):  
Saleem S. Qader ◽  
Javier Jimenez-Feltström ◽  
Mats Ekelund ◽  
Ingmar Lundquist ◽  
Albert Salehi
Keyword(s):  
Nitric Oxide ◽  
Cyclic Amp ◽  
Insulin Release ◽  
Inducible Nitric Oxide Synthase ◽  
Cyclic Gmp ◽  
Inos Expression ◽  
Β Cells ◽  
Lipid Infusion ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Chronic exposure of pancreatic islets to elevated plasma lipids (lipotoxicity) can lead to β-cell dysfunction, with overtime becoming irreversible. We examined, by confocal microscopy and biochemistry, whether the expression of islet inducible nitric oxide synthase (iNOS) and the concomitant inhibition of glucose-stimulated insulin release seen after lipid infusion in rats was modulated by the islet neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP)27. Lipid infusion for 8 days induced a strong expression of islet iNOS, which was mainly confined to β-cells and was still evident after incubating islets at 8.3 mmol/l glucose. This was accompanied by a high iNOS-derived NO generation, a decreased insulin release, and increased cyclic GMP accumulation. No iNOS expression was found in control islets. Addition of PACAP27 to incubated islets from lipid-infused rats resulted in loss of iNOS protein expression, increased cyclic AMP, decreased cyclic GMP, and suppression of the activities of neuronal constitutive (nc)NOS and iNOS and increased glucose-stimulated insulin response. These effects were reversed by the PKA inhibitor H-89. The suppression of islet iNOS expression induced by PACAP27 was not affected by the proteasome inhibitor MG-132, which by itself induced the loss of iNOS protein, making a direct proteasomal involvement less likely. Our results suggest that PACAP27 through its cyclic AMP- and PKA-stimulating capacity strongly suppresses not only ncNOS but, importantly, also the lipid-induced stimulation of iNOS expression, possibly by a nonproteasomal mechanism. Thus PACAP27 restores the impairment of glucose-stimulated insulin release and additionally might induce cytoprotection against deleterious actions of iNOS-derived NO in β-cells.

scholarly journals Activation of Nuclear Factor κB and Induction of Inducible Nitric Oxide Synthase by Ureaplasma urealyticumin Macrophages

2000 ◽  
Vol 68 (12) ◽  
pp. 7087-7093 ◽  
Author(s):  
Y.-H. Li ◽  
Z.-Q. Yan ◽  
J. Skov Jensen ◽  
K. Tullus ◽  
A. Brauner
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Alveolar Macrophages ◽  
Nuclear Factor Κb ◽  
Inos Expression ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

ABSTRACT Chronic lung disease (CLD) of prematurity is an inflammatory disease with a multifactorial etiology. The importance ofUreaplasma urealyticum in the development of CLD is debated, and steroids produce some improvement in neonates with this disease. In the present study, the capability of U. urealyticum to stimulate rat alveolar macrophages to produce nitric oxide (NO), express inducible nitric oxide synthase (iNOS), and activate nuclear factor κB (NF-κB) in vitro was characterized. The effect of NO on the growth of U. urealyticum was also investigated. In addition, the impact of dexamethasone and budesonide on these processes was examined. We found that U. urealyticum antigen (≥4 × 107 color-changing units/ml) stimulated alveolar macrophages to produce NO in a dose- and time-dependent manner (P < 0.05). This effect was further enhanced by gamma interferon (100 IU/ml; P < 0.05) but was attenuated by budesonide and dexamethasone (10−4 to 10−6 M) (P < 0.05). The mRNA and protein levels of iNOS were also induced in response to U. urealyticum and inhibited by steroids.U. urealyticum antigen triggered NF-κB activation, a possible mechanism for the induced iNOS expression, which also was inhibited by steroids. NO induced by U. urealyticum caused a sixfold reduction of its own growth after infection for 10 h. Our findings imply that U. urealyticum may be an important factor in the development of CLD. The host defense response againstU. urealyticum infection may also be influenced by NO. The down-regulatory effect of steroids on NF-κB activation, iNOS expression, and NO production might partly explain the beneficial effect of steroids in neonates with CLD.

Abstract 316: Effects of Inhibiting of Inducible Nitric Oxide Synthase in the Pathophysiology of Experimental Preeclampsia

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Lorena M Amaral ◽  
Ana Carolina T Palei ◽  
Lucas C Pinheiro ◽  
Jonas T Sertorio ◽  
Danielle A Guimaraes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Expression ◽  
Oxygen Species ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The pathophysiology of preeclampsia (PE) is not entirely known. However, increased oxidative stress possibly leading to impaired nitric oxide activity has been implicated in the critical condition. Increased oxidative stress with increased levels of highly reactive species including superoxide may generate peroxynitrite. We examined the role of inducible nitric oxide synthase (iNOS) and oxidative stress in the reduced uterine perfusion pressure (RUPP) preeclampsia experimental model. METHODS: RUPP was induced in wistar rats. Pregnant rats in the RUPP group had their aortic artery clipped at day 14 of gestation. After a midline incision, a silver clip (0.203 mm) was placed around the aorta above the iliac bifurcation; silver clips (0.100 mm) were also placed on branches of both the right and left ovarian arteries that supply the uterus. Sham-operated (pregnant control rats) and RUPP rats were treated with oral vehicle or 1 mg/kg/day 1400W (iNOS inhibitor) for 5 days. Mean arterial pressure (MAP) and plasma levels of thiobarbituric acid-reactive species (TBARS) and total radical-trapping antioxidant potential (TRAP) were measured determined. Aortic iNOS expression (Western blotting) and reactive oxygen species (ROS; assessed by fluorescence microscopy with dihydroethidium-DHE) were measured. We found increased mean arterial pressure in RUPP compared with pregnant control rats (MAP= 128±1 vs. 100±1.8 mmHg, respectively; P<0.05) and 1400W exerted antihypertensive effects (MAP= 114±2 vs.128±1 mmHg in RUPP treated and untreated rats, respectively; P<0.05). Higher reactive oxygen species (ROS) concentrations were found in RUPP compared with pregnant control rats (7.1±0.5 vs. 5.1±0.5 arbitrary units (A.U.), respectively; P<0.05) and 1400W decreased ROS production to 5.8±0.02 A.U. in RUPP treated rats, P<0.05. In addition, 1400W attenuated iNOS expression in RUPP rats (0.29±0.02 vs. 0.55±0.8 A.U. in RUPP treated and untreated rats, respectively; P<0.01) and had no effects on plasma TBARS and TRAP levels. Our results suggest that 1400w exerts antihypertensive effects in the RUPP model and suppresses ROS formation. Supported by FAPESP,Cnpq.

Modulation of hepatic inducible nitric oxide synthase (iNOS) expression by S-adenosylmethionine (AdoMet) in rats

2001 ◽  
Vol 34 ◽  
pp. 83
Author(s):  
P.L. Majano ◽  
C. Garcia-Monzon ◽  
U. Latasa ◽  
E. Garcia-Trevijano ◽  
F.J. Corrales ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Expression ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide
Sign in / Sign up

Export Citation Format

Share Document