scholarly journals Increased ACE Expression and iNOS Protein Levels in the Aorta of 2‐month‐old Syrian Cardiomyopathic Hamsters

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Nildris Cruz ◽  
Jose Quidgley ◽  
Laurianne El Musa ◽  
Juan Garcia ◽  
Giselle Torres ◽  
...  
Keyword(s):  
Inos Protein ◽  
Protein Levels ◽  
Cardiomyopathic Hamsters

Rgx365, a Rare Protopanaxatriol-Type Ginsenoside Fraction from Black Ginseng, Suppresses Inflammatory Gene iNOS via the Iinhibition of p-STAT-1 and NF-κB

2020 ◽  
Vol 48 (05) ◽  
pp. 1091-1102
Author(s):  
So Yeon Jeong ◽  
Ji-Eun Kim ◽  
Gyu-Yong Song ◽  
Jong-Sup Bae
Keyword(s):  
Lung Tissue ◽  
Lavage Fluid ◽  
Heme Oxygenase 1 ◽  
Inos Protein ◽  
Protein Levels ◽  
Rna Transfection ◽  
Inos Protein Expression ◽  
Black Ginseng ◽  
Cox 2 ◽  
Human Pulmonary Artery

Black ginseng (BG), which is ginseng that has been steamed and dried nine times, and its main protopanaxatriol-type ginsenosides Rg4, Rg6, Rh4, and Rg2 have been reported to exhibit various forms of biological activity, including antiseptic, antidiabetic, wound-healing, immune-stimulatory, and anti-oxidant activity. The aim of the this study was to examine the effects of [Formula: see text] (a rare protopanaxatriol-type ginsenoside fraction; Rg2, Rg4, Rg6, Rh1, and Rh4) on heme oxygenase-1 (HO-1) induction and on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-)2 in lipopolysaccharide (LPS)-activated human pulmonary artery endothelial cells (HPAECs). [Formula: see text] was tested to determine its effect on iNOS protein expression and inflammatory markers (interleukin [IL]-1[Formula: see text] and tumor necrosis factor [TNF]-[Formula: see text] in the lung tissue of LPS-treated mice. The results showed that [Formula: see text] induced the expression of HO-1, reduced LPS-activated NF-[Formula: see text]B-luciferase activity, and inhibited iNOS/NO and COX-2/PGE2, which contributed to the inhibition of STAT-1 phosphorylation. In particular, [Formula: see text] induced the translocation of Nrf2 from the cytosol to the nucleus by increasing Nrf2-ARE activity and decreased IL-1[Formula: see text] production in LPS-activated HPAECs. This reduction in iNOS/NO expression due to [Formula: see text] was reversed by siHO-1 RNA transfection. In LPS-treated mice, [Formula: see text] significantly reduced lung tissue iNOS protein levels and TNF-[Formula: see text] levels in the bronchoalveolar lavage fluid. In conclusion, these findings indicate that [Formula: see text] has a critical anti-inflammatory effect due to its ability to regulate iNOS via the inhibition of p-STAT-1 and NF-[Formula: see text]B, and thus it may be suitable for the treatment of inflammatory disease.

scholarly journals NFκB activation and stimulation of chemokine production in normal human macrophages by the gadolinium-based magnetic resonance contrast agent Omniscan: possible role in the pathogenesis of nephrogenic systemic fibrosis

2010 ◽  
Vol 69 (11) ◽  
pp. 2024-2033 ◽  
Author(s):  
Francesco Del Galdo ◽  
Peter J Wermuth ◽  
Sankar Addya ◽  
Paolo Fortina ◽  
Sergio A Jimenez
Keyword(s):  
Gene Expression ◽  
Nephrogenic Systemic Fibrosis ◽  
Specific Cell ◽  
Chemokine Production ◽  
Nuclear Localisation ◽  
Inos Protein ◽  
Protein Levels ◽  
Normal Human ◽  
Stimulation Of

ObjectiveNephrogenic systemic fibrosis (NSF) is a generalised fibrotic disorder occurring in certain individuals with renal insufficiency exposed to gadolinium-based contrast agents (GdBCA) for MRI. Histopathological examination of affected tissues shows increased numbers of activated macrophages. To elucidate the mechanisms responsible for macrophage activation, the effects of the GdBCA Omniscan on normal human macrophage global gene expression, chemokine production and nuclear factor κB (NFκB) activation was examined.MethodsNormal human monocyte-derived macrophages were incubated with Omniscan (50 mM) and their gene expression analysed by microarrays and real-time PCR. Macrophage chemokine production was assayed by multiplex ELISA. NFκB activation was assessed by NFκB nuclear localisation and quantitation of intracellular levels of inducible nitric oxide synthase (iNOS) protein. A specific cell-permeable NFκB peptide inhibitor was used to abrogate NFκB stimulation of chemokine and iNOS protein levels. CCL8/MCP-2 in affected skin of patients with NSF was examined by indirect immunofluorescence.ResultsOmniscan caused a profound change in the transcriptome of differentiated human normal macrophages in vitro, including a large increase in the expression of genes encoding CC and CXC chemokines. It induced rapid nuclear localisation of NFκB and stimulation of iNOS protein levels and chemokine production which were blocked by an NFκB inhibitory peptide. CCL8/MCP-2, the most upregulated chemokine following in vitro macrophage exposure to Omniscan, was strongly increased in NSF-affected skin.ConclusionThe GdBCA Omniscan induces potent stimulation of macrophage gene expression, NFκB activation and increased NFκB-mediated production of CC and CXC chemokines and iNOS. These alterations may play a crucial role in the pathogenesis of NSF.

Upregulation of lung soluble guanylate cyclase during chronic hypoxia is prevented by deletion of eNOS

2001 ◽  
Vol 281 (2) ◽  
pp. L369-L376 ◽  
Author(s):  
Dechun Li ◽  
Victor E. Laubach ◽  
Roger A. Johns
Keyword(s):  
Right Ventricle ◽  
Protein Expression ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Vasculature ◽  
Hypoxic Exposure ◽  
Mouse Lung ◽  
Inos Protein ◽  
Protein Levels ◽  
The Right

Hypoxia upregulates endothelial (e) nitric oxide synthase (NOS), but how eNOS affects soluble guanylate cyclase (sGC) protein expression in hypoxia-induced pulmonary hypertension is unknown. Wild-type (WT), eNOS-deficient [eNOS(−/−)], and inducible NOS (iNOS)-deficient [iNOS(−/−)] mice were used to investigate the effects of lack of NO from different NOS isoforms on sGC activity and protein expression and its relationship to the muscularization of the pulmonary vasculature. After 6 days of hypoxic exposure (10% O2), the ratios of the right ventricle to left ventricle + septum weight (RV/LV+S) and right ventricle weight to body weight, the lung sGC activity, and vascular muscularization were determined, and protein analysis for eNOS, iNOS, and sGC was performed. Results demonstrated that there were significant increases of RV/LV+S in all animals treated with hypoxia. In hypoxic WT and iNOS(−/−) mice, eNOS and sGC α1- and β1-protein increased twofold; cGMP levels and the number of muscularized vessels also increased compared with hypoxic eNOS(−/−) mice. There was a twofold increase of iNOS protein in WT and eNOS(−/−) mice, and the basal iNOS protein concentration was higher in eNOS(−/−) mice than in WT mice. In contrast, the eNOS(−/−) mouse lung showed no eNOS protein expression, lower cGMP concentrations, and no change of sGC protein levels after hypoxic exposure compared with its normoxic controls ( P > 0.34). These results suggest that eNOS, but not iNOS, is a major regulator of sGC activity and protein expression in the pulmonary vasculature.

scholarly journals Developmental Time‐course of Vascular RNA Expression and Protein Levels for ACE, eNOS and iNOS in Young Syrian Cardiomyopathic Hamsters

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Nildris Cruz ◽  
Jose Quidgley ◽  
Juan M. Garcia ◽  
Giselle M. Torres ◽  
Nelson Escobales ◽  
...  
Keyword(s):  
Time Course ◽  
Developmental Time ◽  
Rna Expression ◽  
Protein Levels ◽  
Cardiomyopathic Hamsters

Matrix remodeling in experimental and human heart failure: a possible regulatory role for TIMP-3

2003 ◽  
Vol 284 (2) ◽  
pp. H626-H634 ◽  
Author(s):  
Paul W. M. Fedak ◽  
Svetlana M. Altamentova ◽  
Richard D. Weisel ◽  
Nafiseh Nili ◽  
Nobuhisa Ohno ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Human Heart ◽  
Matrix Remodeling ◽  
Human Heart Failure ◽  
Protein Levels ◽  
Cardiomyopathic Hamsters ◽  
End Stage ◽  
Myocardial Collagen ◽  
Normal Controls

In the failing heart, an imbalance in matrix metalloproteinases (MMPs) and their biological regulators, the tissue inhibitors of MMPs (TIMPs), may result in cardiac dilatation from matrix degradation. We hypothesized that a reduction of myocardial TIMP-3 is associated with adverse matrix remodeling in both human and experimental heart failure. Cardiomyopathic hamsters at age 15 wk (normal), 25 wk (compensated stage), and 35 wk (overt failure) were compared with age-matched normal controls. MMP activity (gelatinase bioassay) was increased in cardiomyopathic hearts ( P = 0.03) and peaked during the transition to overt heart failure. TIMP-3 content (immunoblot) was decreased compared with normal controls (74 ± 5% at 25 wk, 69 ± 10% at 35 wk; P = 0.001) and its reduction was associated with increased MMP activity ( r = −0.6; P = 0.004). TIMP-1 increased progressively ( P = 0.001), whereas TIMP-2, TIMP-4, and MMP protein levels were unchanged. Myocardial collagen (hydroxyproline content) increased with time during the progression to end-stage cardiac failure ( P < 0.0001). Collagen synthesis ([14C]proline uptake) was elevated in cardiomyopathy at 15 and 25 wk ( P < 0.05). The collagen cross-linking ratio (insoluble:soluble collagen) was reduced ( P = 0.003) as the left ventricle dilated. By confocal microscopy restricted to viable myocardium, collagen content was reduced ( P = 0.04) with fragmentation ( P < 0.0001) and thinning ( P = 0.003) of perimysial collagen fibers. Similarly, patients with end-stage congestive heart failure ( n = 7) compared with nonfailing controls ( n = 2) had elevated gelatinase MMP activity ( P = 0.02) associated with isolated reductions in TIMP-3 (55 ± 5% of normal; P = 0.003). Reductions of TIMP-3 parallel adverse matrix remodeling in the cardiomyopathic hamster and the failing human heart. TIMP-3 may contribute to the regulation of myocardial remodeling and its reduction may promote a transition from compensated to end-stage congestive heart failure.

Intratracheal adenoviral-mediated delivery of iNOS decreases pulmonary vasoconstrictor responses in rats

2004 ◽  
Vol 97 (5) ◽  
pp. 1814-1822 ◽  
Author(s):  
Louis G. Chicoine ◽  
Edith Tzeng ◽  
Rebekah Bryan ◽  
Steven Saenz ◽  
Michael L. Paffett ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Exhaled Nitric Oxide ◽  
Time Dependent ◽  
Inos Mrna ◽  
Alveolar Wall ◽  
Gene Transduction ◽  
Inos Protein ◽  
Protein Levels ◽  
Inos Gene ◽  
Adenoviral Construct

We hypothesized that adenovirus-mediated inducible nitric oxide synthase (iNOS) gene transduction of the lung would result in time-dependent iNOS overexpression and attenuate the vascular constrictor responses to a thromboxane mimetic, U-46619. Rats were treated via the trachea with surfactant alone (sham), surfactant containing an adenoviral construct with a cytomegalovirus promoter-regulated human iNOS gene (Adeno-iNOS), or an adenoviral construct without a gene insert (Adeno-Control). Adeno-iNOS-transduced rats demonstrated human iNOS mRNA and increased iNOS protein levels only in the lungs. Immunohistochemistry of lungs from Adeno-iNOS-treated animals demonstrated transgene expression in alveolar wall cells. In the lungs from Adeno-iNOS-transduced rats, the expression of iNOS protein and exhaled nitric oxide concentrations were increased on days 1–4 and 7 but returned to baseline values by day 14. The administration of the selective iNOS inhibitor l- N6-(1-iminoethyl)lysine dihydrochloride (l-NIL) decreased exhaled nitric oxide concentrations to levels found in Adeno-Control-transduced lungs. In a second group of rats, the segmental vasoconstrictor responses to U-46619 were determined in isolated, perfused lungs 3 days after transduction. Lungs from rats transduced with Adeno-iNOS had reduced total, arterial, and venous vasoconstrictor responses to U-46619 compared with sham, Adeno-Control, and control groups. In a third set of experiments, the response to 400 nM U-46619 in the presence of 10 μM l-NIL was not different in the isolated lungs from Adeno-Control- and Adeno-iNOS-transduced rats. We conclude that adenovirus-mediated iNOS gene transduction of the lung results in time-dependent iNOS overexpression, which attenuates the vascular constrictor responses to the thromboxane mimetic U-46619.

Vitamin B6 Deficiency can Reduce Fuel Storage and Utilization in Physically Trained Rats

2008 ◽  
Vol 78 (2) ◽  
pp. 64-69 ◽  
Author(s):  
Choi ◽  
Cho
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Muscle Protein ◽  
Plasma Free Fatty Acid ◽  
Vitamin B ◽  
Liver Protein ◽  
Protein Levels ◽  
Before And After ◽  
Fuel Storage ◽  
Exercise Muscle

This study investigated the effect of vitamin B6 deficiency on the utilization and recuperation of stored fuel in physically trained rats. 48 rats were given either vitamin B6-deficient (B6–) diet or control (B6+) diet for 4 weeks and were trained on treadmill for 30 minutes daily. All animals were then subdivided into 3 groups: before-exercise (BE); during-exercise (DE); after-exercise (AE). The DE group was exercised on treadmill for 1 hour just before being sacrificed. Animals in the AE group were allowed to take a rest for 2 hours after being exercised like the DE group. Glucose and free fatty acids were compared in plasma. Glycogen and triglyceride were compared in liver and skeletal muscle. Protein levels were compared in plasma, liver, and skeletal muscle. Compared with the B6+ group, plasma glucose levels of the B6– group were significantly lower before and after exercise. Muscle glycogen levels of the B6– group were significantly lower than those of the B6+ group regardless of exercise. The liver glycogen level of the B6– group was also significantly lower than that of B6+ group during and after exercise. Before exercise, plasma free fatty acid levels were not significantly different between the B6+ and B6– groups, and plasma free fatty acid levels of the B6– group were significantly lower during and after exercise. The muscle triglyceride level of the B6– group was significantly lower than that of the B6+ group before exercise, and there were no differences between B6+ and B6– groups during and after exercise. Liver triglyceride levels were not significantly different between B6+ and B6– groups. Plasma protein levels of the B6– group were lower than those of B6+ before and after exercise. Muscle protein levels of the B6– group were not significantly different from those of the B6+ group. Liver protein levels of the B6– group were significantly lower than that of the B6+ group after exercise. Liver protein levels of both B6+ and B6– groups were not significantly changed, regardless of exercise. Thus, it is suggested that vitamin B6 deficiency may reduce fuel storage and utilization with exercise in physically trained rats.

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