scholarly journals Paraoxonases-2 and -3 Are Important Defense Enzymes againstPseudomonas aeruginosaVirulence Factors due to Their Anti-Oxidative and Anti-Inflammatory Properties

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Eva-Maria Schweikert ◽  
Julianna Amort ◽  
Petra Wilgenbus ◽  
Ulrich Förstermann ◽  
John F. Teiber ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanism ◽  
Homoserine Lactone ◽  
Host Cells ◽  
Defense System ◽  
Innate Defense ◽  
Redox Active ◽  
Intracellular Ca ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

The pathogenPseudomonas aeruginosacauses serious damage in immunocompromised patients by secretion of various virulence factors, among them the quorum sensing N-(3-oxododecanoyl)-L-homoserine lactone (3OC12) and the redox-active pyocyanin (PCN). Paraoxonase-2 (PON2) may protect againstP. aeruginosainfections, as it efficiently inactivates 3OC12 and diminishes PCN-induced oxidative stress. This defense could be circumvented because 3OC12 mediates intracellular Ca2+-rise in host cells, which causes rapid inactivation and degradation of PON2. Importantly, we recently found that the PON2 paralogue PON3 prevents mitochondrial radical formation. Here we investigated its role as additional potential defense mechanism againstP. aeruginosainfections. Our studies demonstrate that PON3 diminished PCN-induced oxidative stress. Moreover, it showed clear anti-inflammatory potential by protecting against NF-κB activation and IL-8 release. The latter similarly applied to PON2. Furthermore, we observed a Ca2+-mediated inactivation and degradation of PON3, again in accordance with previous findings for PON2. Our results suggest that the anti-oxidative and anti-inflammatory functions of PON2 and PON3 are an important part of our innate defense system againstP. aeruginosainfections. Furthermore, we conclude thatP. aeruginosacircumvents PON3 protection by the same pathway as for PON2. This may help identifying underlying mechanisms in order to sustain the protection afforded by these enzymes.

Paraoxonase 2 is down-regulated by the Pseudomonas aeruginosa quorumsensing signal N-(3-oxododecanoyl)-L-homoserine lactone and attenuates oxidative stress induced by pyocyanin

2010 ◽  
Vol 426 (1) ◽  
pp. 73-83 ◽  
Author(s):  
Sven Horke ◽  
Ines Witte ◽  
Sebastian Altenhöfer ◽  
Petra Wilgenbus ◽  
Marion Goldeck ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Pseudomonas Aeruginosa ◽  
Homoserine Lactone ◽  
Hydrolytic Activity ◽  
Host Cells ◽  
Ionophore A23187 ◽  
Acetoxymethyl Ester ◽  
Bacterial Gene ◽  
Bacterial Gene Expression ◽  
Ros Formation

Two virulence factors produced by Pseudomonas aeruginosa are pyocyanin and N-(3-oxododecanoyl)-L-homoserine lactone (3OC12). Pyocyanin damages host cells by generating ROS (reactive oxygen species). 3OC12 is a quorum-sensing signalling molecule which regulates bacterial gene expression and modulates host immune responses. PON2 (paraoxonase-2) is an esterase that inactivates 3OC12 and potentially attenuates Ps. aeruginosa virulence. Because increased intracellular Ca2+ initiates the degradation of PON2 mRNA and protein and 3OC12 causes increases in cytosolic Ca2+, we hypothesized that 3OC12 would also down-regulate PON2. 3OC12 and the Ca2+ ionophore A23187 caused a rapid cytosolic Ca2+ influx and down-regulated PON2 mRNA, protein and hydrolytic activity in A549 and EA.hy 926 cells. The decrease in PON2 hydrolytic activity was much more extensive and rapid than decreases in protein, suggesting a rapid post-translational mechanism which blocks PON2's hydrolytic activity. The Ca2+ chelator BAPTA/AM [1,2-bis-(o-aminophenoxy)ethane-N,N,N′,N′-tetra-acetic acid tetrakis(acetoxymethyl ester)] diminished the ability of 3OC12 to decrease PON2, demonstrating that the effects are mediated by Ca2+. PON2 also has antioxidative properties and we show that it protects cells from pyocyanin-induced oxidative stress. Knockdown of PON2 by transfecting cells with siRNA (small interfering RNA) rendered them more sensitive to, whereas overexpression of PON2 protected cells from, pyocyanin-induced ROS formation. Additionally, 3OC12 potentiated pyocyanin-induced ROS formation, presumably by inactivating PON2. These findings support a key role for PON2 in the defence against Ps. aeruginosa virulence, but also reveal a mechanism by which the bacterium may subvert the protection afforded by PON2.

scholarly journals Protective roles of redox-active protein thioredoxin-1 for severe acute pancreatitis

2006 ◽  
Vol 290 (4) ◽  
pp. G772-G781 ◽  
Author(s):  
Shinya Ohashi ◽  
Akiyoshi Nishio ◽  
Hajime Nakamura ◽  
Masahiro Kido ◽  
Satoru Ueno ◽  
...  
Keyword(s):  
Acute Pancreatitis ◽  
Severe Acute Pancreatitis ◽  
Defense Mechanism ◽  
Intraperitoneal Administration ◽  
Neutrophil Infiltration ◽  
Myeloperoxidase Activity ◽  
Experimental Acute Pancreatitis ◽  
Redox Active ◽  
Thioredoxin 1 ◽  
Anti Inflammatory

Severe acute pancreatitis is a disease with high mortality, and infiltration of inflammatory cells and reactive oxygen species have a crucial role in the pathophysiology of this disease. Thioredoxin-1 (TRX-1) is an endogenous redox-active multifunctional protein with antioxidant and anti-inflammatory effects. TRX-1 is induced in various inflammatory conditions and shows cytoprotective effects. The aim of the present study was to clarify the protective roles of TRX-1 in the host defense mechanism against severe acute pancreatitis. Experimental acute pancreatitis was induced by intraperitoneal administration of cerulein, a CCK analog, and aggravated by lipopolysaccharide injection in transgenic mice overexpressing human TRX-1 (hTRX-1) and control C57BL/6 mice. Transgenic overexpression of hTRX-1 strikingly attenuated the severity of experimental acute pancreatitis. TRX-1 overexpression suppressed neutrophil infiltration as determined by myeloperoxidase activity, oxidative stress as determined by malondialdehyde concentration, and cytoplasmic degradation of inhibitor of κB-α, thereby suppressing proinflammatory cytokines, tumor necrosis factor-α, interleukin-1β, and interleukin-6; a neutrophil chemoattractant, keratinocyte-derived chemokine; and inducible nitric oxide synthase in the pancreas. Administration of recombinant hTRX-1 also suppressed neutrophil infiltration, reduced the inflammation of the pancreas and the lung, and improved the mortality rate. The present study suggests that TRX-1 has potent antioxidant and anti-inflammatory actions in experimental acute pancreatitis and might be a new therapeutic strategy to improve the prognosis of severe acute pancreatitis.

scholarly journals Anti-Inflammatory Effects of Analogues of N-Acyl Homoserine Lactones on Eukaryotic Cells

2020 ◽  
Vol 21 (24) ◽  
pp. 9448
Author(s):  
Agathe Peyrottes ◽  
Garance Coquant ◽  
Loïc Brot ◽  
Dominique Rainteau ◽  
Philippe Seksik ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Cell Model ◽  
Homoserine Lactone ◽  
Biological Properties ◽  
Host Cells ◽  
Medical Community ◽  
Eukaryotic Cells ◽  
Reporter Strain ◽  
Ifn Γ ◽  
Anti Inflammatory

Background: Since acyl-homoserine lactone (AHL) profiling has been described in the gut of healthy subjects and patients with inflammatory bowel disease (IBD), the potential effects of these molecules on host cells have raised interest in the medical community. In particular, natural AHLs such as the 3-oxo-C12-HSL exhibit anti-inflammatory properties. Our study aimed at finding stable 3-oxo-C12-HSL-derived analogues with improved anti-inflammatory effects on epithelial and immune cells. Methods: We first studied the stability and biological properties of the natural 3-oxo-C12-HSL on eukaryotic cells and a bacterial reporter strain. We then constructed and screened a library of 22 AHL-derived molecules. Anti-inflammatory effects were assessed by cytokine release in an epithelial cell model, Caco-2, and a murine macrophage cell line, RAW264.7, (respectively, IL-8 and IL-6) upon exposure to the molecule and after appropriate stimulation (respectively, TNF-α 50 ng/mL and IFN-γ 50 ng/mL, and LPS 10 ng/mL and IFN-γ 20 U/mL). Results: We found two molecules of interest with amplified anti-inflammatory effects on mammalian cells without bacterial-activating properties in the reporter strain. The molecules furthermore showed improved stability in biological medium compared to the native 3-oxo-C12-HSL. Conclusions: We provide new bio-inspired AHL analogues with strong anti-inflammatory properties that will need further study from a therapeutic perspective.

scholarly journals Influence of Pinealectomy and Long-term Melatonin Administration on Inflammation and Oxidative Stress in Experimental Gouty Arthritis

2021 ◽  
Author(s):  
Arwa Fadıl Haqi BALLUR ◽  
Eyup ALTINOZ ◽  
Gurkan YİGİTTURK ◽  
Melike Ozgul Onal ◽  
Hulya ELBE ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gouty Arthritis ◽  
Total Antioxidant Status ◽  
Cellular Damage ◽  
Histopathological Changes ◽  
Markers Of Inflammation ◽  
Antioxidant Defense Systems ◽  
Anti Inflammatory ◽  
Underlying Mechanisms ◽  
Msu Crystals

Abstract Gout is an inflammatory arthritis characterized by the deposition of monosodium urate (MSU) crystals in the joints or soft tissue. MSU crystals are potent inflammation inducers. Melatonin (MLT) is a powerful endogenous anti-inflammatory agent and effective in reducing cellular damage. In the present study, possible underlying mechanisms associated with anti-inflammatory and anti-oxidative effects were investigated in rats with gouty arthritis and melatonin deprivation treated with MLT. Fifty-six rats were divided into seven groups: control, sham control, pinealectomy (PNX), MSU (On the 30th day, single dose 20 mg/ml, intraperitoneal), MSU+MLT (10 mg/kg/day for 30 days, intraperitoneal), MSU+PINX and MSU+PINX+MLT. PNX procedure was performed on the first day of the study. As compared to the controls, the results showed that MSU administration caused significant increases in oxidative stress parameters (malondialdehyde and total oxidant status). Besides, significant decreases in antioxidant defense systems (glutathione, superoxide dismutase and total antioxidant status were observed. A statistically significant increase was found in the mean histopathological damage score in the groups that received MSU injection. It was found that histopathological changes were significantly reduced in the MSU+MLT group given MLT. In our study, it was determined that many histopathological changes, as well as swelling and temperature increase in the joint, which are markers of inflammation, were significantly reduced with MLT supplementation. These results suggest that melatonin ameliorates MSU-induced gout in the rat through inhibition of oxidative stress and proinflammatory cytokine production.

Inhaled Carbon Monoxide: An Anti-Inflammatory Modulator in Transgenic Sickle Mice.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2268-2268
Author(s):  
Joan D. Beckman ◽  
Julie V. Vineyard ◽  
Casey Yang ◽  
Thomas E. Schmidt ◽  
John D. Belcher ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Carbon Monoxide ◽  
Critical Role ◽  
Prolonged Treatment ◽  
Heme Oxygenase 1 ◽  
Western Blots ◽  
Active Iron ◽  
Redox Active ◽  
Significant Difference ◽  
Anti Inflammatory

Abstract Inflammation plays a prominent role in vaso-occlusion and organ pathology in sickle cell disease (SCD). We have shown that heme oxygenase-1 (HO-1) plays a critical role in metabolizing the excess heme generated in this hemolytic disease, thereby modulating hypoxia/reoxygenation-induced vaso-occlusion in murine models of SCD. The products of HO-1 activity, carbon monoxide (CO), Fe2+ (ultimately incorporated into ferritin), and biliverdin/bilirubin have demonstrable anti-oxidant and anti-inflammatory effects. We have observed that brief (1 h/d × 3 d) inhalation of CO in SCD mice modulates vaso-occlusion (JCI, 116: 808–816; 2006). We hypothesize that prolonged treatment with inhaled CO will significantly decrease the inflammatory phenotype of SCD mice. Starting at three weeks of age, C57BL-6J and heterozygous BERK mice (mβ/hβS) were treated with inhaled CO at 0, 25, or 250 ppm (1 h/d × 3 d/wk × 10 wks). Over the duration of the ten week study no animals died as result of the CO treatments. Upon completion of the ten week treatment period animals were euthanized, blood was removed by cardiac puncture, and organs were harvested and homogenized. Carboxyhemoglobin levels immediately after 1h of CO treatment, (0, 25, and 250 ppm) were <1%,<1%, and 12%, respectively, but decreased to normal 24 h later. Untreated heterozygous BERK mice had a higher mean white blood cell count (WBC)(14,400/μL) than C57BL-6J mice (9,469/ μL, p<0.005). Treatment for 10 weeks with either 25 or 250 ppm CO significantly decreased heterozygous BERK WBC (8827 and 9222/μl, p<0.02), but had no effect on C57BL-6J WBC. The decrement in heterozygous BERK WBC was primarily due to a significant decrease in neutrophils (p<0.05). There was no significant difference in either the mean hematocrits or reticulocyte counts in CO-treated mice. Since redox-active iron (Fe2+) promotes oxidative stress and inflammation, we measured redox-active iron with Ferene-S in liver homogenates. In untreated heterozygous BERK mice, redox-active iron was two-fold greater than C57BL-6J mice (p<0.05) and treatment with 25 or 250 ppm CO significantly (p<0.01, p<0.02 respectively) decreased the redox-active iron (Fe2+) to levels comparable to untreated C57BL-6J. Since there is red cell congestion in heterozygous BERK livers, it was not surprising that the heme-content of untreated heterozygous BERK mice was three-fold (p<0.05) higher than untreated C57BL-6J. Treatment with 25 or 250 ppm CO significantly (p<0.05) decreased the heme-content of the livers to levels comparable to untreated C57BL-6J. The cytoprotective proteins HO-1 and ferritin heavy-chain were significantly increased in the livers of untreated heterozygous BERK mice compared to C57BL-6J (p<0.02). However, CO treatments had no significant effects on expression of these proteins on Western blots. We conclude that inhaled CO treatments decrease WBC, neutrophils, as well as liver redox-active iron and heme content in heterozygous BERK mice. Further studies are evaluating the effects of CO on inflammation, vaso-occlusion, and organ pathology in the homozygous BERK mouse model. We speculate that inhaled CO treatments may be a potential therapy for patients with SCD by acting as a modulator of oxidative stress and inflammation.

scholarly journals Melatonin Mediated Regulation of Drought Stress: Physiological and Molecular Aspects

Plants ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 190 ◽  
Author(s):  
Sharma ◽  
Zheng
Keyword(s):  
Oxidative Stress ◽  
Drought Stress ◽  
Photosynthetic Apparatus ◽  
Severe Drought ◽  
Defense System ◽  
Ros Scavenging ◽  
Effects Of Drought ◽  
Molecular Aspects ◽  
Underlying Mechanisms ◽  
Scavenging Efficiency

Drought stress adversely effects physiological and biochemical processes of plants, leading to a reduction in plant productivity. Plants try to protect themselves via activation of their internal defense system, but severe drought causes dysfunction of this defense system. The imbalance between generation and scavenging of reactive oxygen species (ROS) leads to oxidative stress. Melatonin, a multifunctional molecule, has the potential to protect plants from the adverse effects of drought stress by enhancing the ROS scavenging efficiency. It helps in protection of photosynthetic apparatus and reduction of drought induced oxidative stress. Melatonin regulates plant processes at a molecular level, which results in providing better resistance against drought stress. In this review, the authors have discussed various physiological and molecular aspects regulated by melatonin in plants under drought conditions, along with their underlying mechanisms.

scholarly journals Oral Exposure to Atrazine Induces Oxidative Stress and Calcium Homeostasis Disruption in Spleen of Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Shuying Gao ◽  
Zhichun Wang ◽  
Chonghua Zhang ◽  
Liming Jia ◽  
Yang Zhang
Keyword(s):  
Oxidative Stress ◽  
Calcium Homeostasis ◽  
Protein Product ◽  
Oral Exposure ◽  
Advanced Oxidation Protein Product ◽  
Expression Of Genes ◽  
Intracellular Ca ◽  
Herbicide Atrazine ◽  
Underlying Mechanisms

The widely used herbicide atrazine (ATR) can cause many adverse effects including immunotoxicity, but the underlying mechanisms are not fully understood. The current study investigated the role of oxidative stress and calcium homeostasis in ATR-induced immunotoxicity in mice. ATR at doses of 0, 100, 200, or 400 mg/kg body weight was administered to Balb/c mice daily for 21 days by oral gavage. The studies performed 24 hr after the final exposure showed that ATR could induce the generation of reactive oxygen species in the spleen of the mice, increase the level of advanced oxidation protein product (AOPP) in the host serum, and cause the depletion of reduced glutathione in the serum, each in a dose-related manner. In addition, DNA damage was observed in isolated splenocytes as evidenced by increase in DNA comet tail formation. ATR exposure also caused increases in intracellular Ca2+within splenocytes. Moreover, ATR treatment led to increased expression of genes for some antioxidant enzymes, such asHO-1andGpx1, as well as increased expression of NF-κB and Ref-1 proteins in the spleen. In conclusion, it appears that oxidative stress and disruptions in calcium homeostasis might play an important role in the induction of immunotoxicity in mice by ATR.

Rapamycin alleviates oxidative stress-induced damage in rat erythrocytes

2016 ◽  
Vol 94 (5) ◽  
pp. 471-479 ◽  
Author(s):  
Abhishek Kumar Singh ◽  
Sandeep Singh ◽  
Geetika Garg ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Defense Mechanism ◽  
Osmotic Fragility ◽  
Redox System ◽  
Protein Carbonyl ◽  
Ros Production ◽  
Rat Erythrocytes ◽  
Immunosuppressant Drug ◽  
Reducing Ability ◽  
Intracellular Ca

An imbalanced cellular redox system promotes the production of reactive oxygen species (ROS) that may lead to oxidative stress-mediated cell death. Erythrocytes are the best-studied model of antioxidant defense mechanism. The present study was undertaken to investigate the effect of the immunosuppressant drug rapamycin, an inducer of autophagy, on redox balance of erythrocytes and blood plasma of oxidatively challenged rats. Male Wistar rats were oxidatively challenged with HgCl2 (5 mg/kg body mass (b.m.)). A significant (p < 0.05) induction in ROS production, plasma membrane redox system (PMRS), intracellular Ca2+ influx, lipid peroxidation (LPO), osmotic fragility, plasma protein carbonyl (PCO) content, and plasma advanced oxidation protein products (AOPP) and simultaneously significant reduction in glutathione (GSH) level and ferric reducing ability of plasma (FRAP) were observed in rats exposed to HgCl2. Furthermore, rapamycin (0.5 mg/kg b.m.) provided significant protection against HgCl2-induced alterations in rat erythrocytes and plasma by reducing ROS production, PMRS activity, intracellular Ca2+ influx, LPO, osmotic fragility, PCO content, and AOPP and also restored the level of antioxidant GSH and FRAP. Our observations provide evidence that rapamycin improves redox status and attenuates oxidative stress in oxidatively challenged rats. Our data also demonstrate that rapamycin is a comparatively safe immunosuppressant drug.

Inflammatory Biomarkers in Atrial Fibrillation

2019 ◽  
Vol 26 (5) ◽  
pp. 837-854 ◽  
Author(s):  
Effimia Zacharia ◽  
Nikolaos Papageorgiou ◽  
Adam Ioannou ◽  
Gerasimos Siasos ◽  
Spyridon Papaioannou ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Plasma Levels ◽  
Large Scale ◽  
Inflammatory Biomarkers ◽  
Inflammatory Pathways ◽  
Inflammatory State ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

During the last few years, a significant number of studies have attempted to clarify the underlying mechanisms that lead to the presentation of atrial fibrillation (AF). Inflammation is a key component of the pathophysiological processes that lead to the development of AF; the amplification of inflammatory pathways triggers AF, and, in tandem, AF increases the inflammatory state. Indeed, the plasma levels of several inflammatory biomarkers are elevated in patients with AF. In addition, the levels of specific inflammatory biomarkers may provide information regarding to the AF duration. Several small studies have assessed the role of anti-inflammatory treatment in atrial fibrillation but the results have been contradictory. Large-scale studies are needed to evaluate the role of inflammation in AF and whether anti-inflammatory medications should be routinely administered to patients with AF.

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4626-4638 ◽  
Author(s):  
Reyhaneh Moradi-Marjaneh ◽  
Seyed M. Hassanian ◽  
Farzad Rahmani ◽  
Seyed H. Aghaee-Bakhtiari ◽  
Amir Avan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Therapeutic Potential ◽  
Vegf Signaling ◽  
Anticancer Effects ◽  
Inhibition Of Angiogenesis ◽  
Underlying Mechanisms ◽  
Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

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