The Effect of Lipopolysaccharide from Proteus mirabilis on the Level of the Stable End Metabolic Products of Nitric Oxide in Blood Platelets

Saluk-Juszczak, Joanna; Olas, Beata; Nowak, Paweł; Kołodziejczyk, Joanna; Wachowicz, Barbara; Zgirski, Alojzy

doi:10.1007/s00284-006-0230-3

Cited by 12 publications

(6 citation statements)

References 24 publications

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“…The classical effects of NO are dependent on sGC activation, which converts GTP to cGMP further activating PKG . Our data showed that intraplatelet levels of cGMP in ADP‐activated platelets after LPS treatment are significantly higher than the saline group, which is consistent with a previous study . Incubation of platelets from the LPS group with either the sGC inhibitor ODQ or the PKG inhibitor RP‐8‐Br significantly reduced the increased ROS production, indicating that both enzymes form part of the machinery that leads to ROS production in endotoxaemia model.…”

Section: Discussionsupporting

confidence: 91%

Signalling pathways involved in p47^phox‐dependent reactive oxygen species in platelets of endotoxemic rats

Pires

Naime

Oliveira

et al. 2018

Basic Clin Pharma Tox

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Thrombocytopenia during sepsis is associated with a less favourable clinical outcome. Overproduction of reactive oxygen species (ROS) by different cell types contributes to sepsis. Platelets generate ROS, but the upstream pathways of NADPH oxidase activation are not completely understood. Here, we designed experiments in washed platelets from lipopolysaccharide (LPS)-treated rats to investigate the p47 phox activation and ROS generation, and its modulation by c-Src family kinase (c-Src), phosphoinositide 3-kinase (PI3K), protein kinase C (PKC) and protein kinase G (PKG). Rats were injected intraperitoneally with LPS (1 mg/kg), and at 48 hours thereafter, arterial blood was collected and washed platelets were obtained. Washed platelets were pre-incubated with different inhibitors and subsequently activated or not with ADP. Flow cytometry, Western blotting and ELISA were performed. We found that LPS significantly increased the p47 phox phosphorylation and ROS generation compared with the control group (P < 0.05). The enhanced ROS production in the LPS group was unaffected by the non-selective SFKs inhibitor PP2, the PI3K inhibitor wortmannin or the Akt inhibitor PPI-1. The cyclic GMP levels were 115% higher in activated platelets of LPS compared with the saline group (P < 0.05). Moreover, in the LPS group, the sGC inhibitor ODQ, the PKG inhibitor Rp-8-Br and the PKC inhibitor GF109203X abrogated the increased p47 phox phosphorylation and reduced the ROS levels. In conclusion, selective inhibitors of cGMP-PKG and PKC-p47 phox pathways that regulate ROS generation by LPS in platelets may help control the redox balance in sepsis improving the survival of patients.

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Section: Discussionsupporting

confidence: 91%

Signalling pathways involved in p47^phox‐dependent reactive oxygen species in platelets of endotoxemic rats

Pires

Naime

Oliveira

et al. 2018

Basic Clin Pharma Tox

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“…6 Exposure of host cells to LPS can induce an inflammatory response. 7 Upon stimulation, LPS binding to the CD14-Toll-like receptor 4 (TLR4) complex…”

Section: Introductionmentioning

confidence: 99%

Lipopolysaccharide‐induced miR‐1224 negatively regulates tumour necrosis factor‐α gene expression by modulating Sp1

Niu¹,

Mo²,

Qin³

et al. 2011

Immunology

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Summary The innate immune response provides the initial defence mechanism against infection by other organisms. However, an excessive immune response will cause damage to host tissues. In an attempt to identify microRNAs (miRNAs) that regulate the innate immune response in inflammation and homeostasis, we examined the differential expression of miRNAs using microarray analysis in the spleens of mice injected intraperitoneally with lipopolysaccharide (LPS) and saline, respectively. Following challenge, we observed 19 miRNAs up‐regulated (1·5‐fold) in response to LPS. Among these miRNAs, miR‐1224, whose expression level increased 5·7‐fold 6 hr after LPS injection and 2·3‐fold after 24 hr, was selected for further study. Tissue expression patterns showed that mouse miR‐1224 is highly expressed in mouse spleen, kidney and lung. Transfection of miR‐1224 mimics resulted in a decrease in basal tumour necrosis factor‐α (TNF‐α) promoter reporter gene activity and a down‐regulation of LPS‐induced TNF‐α mRNA in RAW264.7 cells. With public databases of miRNA target prediction, miR‐1224 was shown to bind to the 3′ untranslated region (UTR) of Sp1 mRNA, whose coding product controls TNF‐α expression at the transcriptional level. Furthermore, we found that in HEK‐293 cells, the activity of the luciferase reporter bearing Sp1 mRNA 3′ UTR was down‐regulated significantly when transfected with miR‐1224 mimics. After transfection of miR‐1224 in RAW264.7 cells, nucleus Sp1 protein level decreased, and when endogenous miR‐1224 was blocked, the decrease was abolished. Therefore, we initially speculated that miR‐1224 was a negative regulator of TNF‐α in an Sp1‐dependent manner, which was confirmed in vivo by chromatin immunoprecipitation assay, and might be involved in regulating the LPS‐mediated inflammatory responses.

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“…This could indicate that the treatment with spectinomycin could have limited the growing of E. coli in the patients from the treated group and it would have permitted the overproduction of P. mirabilis. P. mirabilis is able to produce endotoxin that can impair diverse biological functions through several mechanisms, as the alteration of platelet activity (Saluk-Juszczak et al, 2007). In the treated lambs the concentration of endotoxin in serum was significantly higher than in the untreated group (Table 1).…”

Section: Discussionmentioning

confidence: 97%

Relationship between the treatment and the evolution of the clinical course in scouring Merino lambs from “La Serena” (Southwest Spain)

Gómez

Andrés

Sánchez

et al. 2008

Small Ruminant Research

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This work investigated the link between the type of treatment and the clinical evolution of lambs suffering from diarrhoea attributed to non-enterotoxigenic Escherichia coli. Two hundred and forty scouring lambs, and 25 healthy lambs selected as control, were used in this trial. The faecal samples from the scouring lambs were positive to non-enterotoxigenic E. coli. All the scouring lambs received supportive care and they were randomly allotted to two groups of 120 animals (treated group and untreated group). The lambs in the treated group were given two daily doses of 20 mg/kg live weight spectinomycin for 3 days, while the other group of lambs (untreated group) did not receive any antibiotic. Serum endotoxin was higher in the treated lambs. The combined infection of E. coli + Proteus mirabilis was the most frequent microbiological result in the deceased treated lambs, while the only enteric pathogen isolated in the untreated lambs submitted to necroscopy was E. coli. The pathological findings most commonly recorded in the untreated lambs were suggestive of a generalized inflammatory process attributed to colibacilosis, while the lesions in the treated lambs might correspond to an enterotoxoemic process. The overproduction of P. mirabilis might be consequence of the antibiotic treatment and it would be the most probable cause of the endotoxemia, the high mortality rate and the pathological findings in the treated lambs. Therefore, a supportive care without antibiotics does not lead to a poorer chance of survival in lambs with diarrhoea attributed to non-enterotoxigenic E. coli.

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The Effect of Lipopolysaccharide from Proteus mirabilis on the Level of the Stable End Metabolic Products of Nitric Oxide in Blood Platelets

Cited by 12 publications

References 24 publications

Signalling pathways involved in p47^phox‐dependent reactive oxygen species in platelets of endotoxemic rats

Signalling pathways involved in p47^phox‐dependent reactive oxygen species in platelets of endotoxemic rats

Lipopolysaccharide‐induced miR‐1224 negatively regulates tumour necrosis factor‐α gene expression by modulating Sp1

Relationship between the treatment and the evolution of the clinical course in scouring Merino lambs from “La Serena” (Southwest Spain)

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The Effect of Lipopolysaccharide from Proteus mirabilis on the Level of the Stable End Metabolic Products of Nitric Oxide in Blood Platelets

Cited by 12 publications

References 24 publications

Signalling pathways involved in p47phox‐dependent reactive oxygen species in platelets of endotoxemic rats

Signalling pathways involved in p47phox‐dependent reactive oxygen species in platelets of endotoxemic rats

Lipopolysaccharide‐induced miR‐1224 negatively regulates tumour necrosis factor‐α gene expression by modulating Sp1

Relationship between the treatment and the evolution of the clinical course in scouring Merino lambs from “La Serena” (Southwest Spain)

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Product

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Signalling pathways involved in p47^phox‐dependent reactive oxygen species in platelets of endotoxemic rats

Signalling pathways involved in p47^phox‐dependent reactive oxygen species in platelets of endotoxemic rats