Novel single nucleotide polymorphism markers for low dose aspirin-associated small bowel bleeding
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ABSTRACT: Blood from 17 patients taking enteric-coated low-dose aspirin (LDA) and with suspected bleeding from small intestine and 18 control patients taking aspirin were analyzed. Results provide insight into the risk for aspirin-induced small bowel bleeding. 35 samples; 1 array per sample.
Project description:Blood from 17 patients taking enteric-coated low-dose aspirin (LDA) and with suspected bleeding from small intestine and 18 control patients taking aspirin were analyzed. Results provide insight into the risk for aspirin-induced small bowel bleeding.
Project description:STOX1 overexpressing placentas generate preeclampsia-like symptoms in pregnant mice. These symptoms are reverted by aspirin. The experiment aims at analyzing placental expression in Transgenic/non transgenic with and withou aspirin, in the placentas at 16,5 days post-coïtum. There are two strains of transgenic mice that express the transgene at different levels: STOX42 about 15 fold that of STOX13. STOX13 expressed the human STOX1 roughly at the level of the mouse endogeneous Stox1 in the placenta.
Project description:Aspirin is currently the only drug used in preeclampsia, a major hypertensive disorder of pregnancy. The counselled doses are low (75-150 mg/day), and the actual effects of aspirin are not well understood, especially in the target organ, the placenta.This is the aim of the present study.
Project description:Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino-acid side-chains, leading to speculation that aspirin-mediated lysine acetylation could explain some of its drug actions or side-effects. Using a labeled form of aspirin, aspirin-d3, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies acetylation signals at thousands of sites, cells tolerate aspirin mediated acetylation very well unless endogenous deacetylases are inhibited. Apart from a limited number of cellular proteins that are substantially acetylated under endogenous conditions, aspirin mediated acetylation leads to a large increase in the acetylation of many proteins even although they remain at very low stoichiometry. This reinforces the idea that a major function of cellular deacetylases is the suppression of non-specific or non-enzymatic protein acetylation.
Project description:Thioredoxin Reductase 1 (isoform 4) was incubated with aspirin for 1 hour at 37 C followed by SDS PAGE. Samples were picked from SDS PAGE gel, digested with trypsin, and sent for LC-MS/MS.
Project description:Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino-acid side-chains, leading to speculation that aspirin-mediated lysine acetylation could explain some of its drug actions or side-effects. Using a labeled form of aspirin, aspirin-d3, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies acetylation signals at thousands of sites, cells tolerate aspirin mediated acetylation very well unless endogenous deacetylases are inhibited. Apart from a limited number of cellular proteins that are substantially acetylated under endogenous conditions, aspirin mediated acetylation leads to a large increase in the acetylation of many proteins even although they remain at very low stoichiometry. This reinforces the idea that a major function of cellular deacetylases is the suppression of non-specific or non-enzymatic protein acetylation.
Project description:Aspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. An important property of aspirin is its ability to acetylate multiple cellular proteins with some pharmacological functions explicable by the irreversible acetylation of cyclooxygenases at active site serine residues. We have used a labeled form of aspirin, aspirin-d3 to acetylate proteins in cultured human cells, and unambiguously identified over 12000 sites of acetylation, using acetylated lysine peptide enrichment combined with mass-spectrometry-based proteomics. Aspirin increases lysine acetylation occupancy of the majority of detected endogenous sites, but leaves almost unchanged a small group that are already highly acetylated. We show that cells are remarkably tolerant of this acetylation insult unless endogenous deacetylases are inhibited. This work raises the possibility that rather than single protein effects, some of the clinical features of aspirin may be the consequence of multiple concurrent protein modifications, and that combining aspirin with lysine deacetylase inhibitors may have important medical implications.
Project description:Pancreatic cancer is a highly malignant tumor that is well known for its poor prognosis. It has been reported that aspirin can reduce the risk of various cancers, but the potential role of aspirin and gemcitabine in pancreatic cancer pathogenesis and chemotherapy has not been studied. Therefore, we investigated their synergistic anti-tumor effects and explored the potential molecular mechanisms and biological functions underlying their inhibitory effects on the development of pancreatic cancer in the hope of identifying treatment-related or prognostic biomarkers for the effective treatment of pancreatic cancer.
Project description:The main aim of this study is to decipher the mutual impact that high glucose levels and diabetes have on aspirin-mediated acetylation of COX-1 through a targeted parallel reaction monitoring MS approach.
Project description:Transcriptome analysis of partially degraded and fragmented RNA samples from mus musculus gut Global gene expression profiling has shown the gut transcripts changes through administration of aspirin while probiotics strain administration beforehand attenuates the effect more than teprenone. We analyzed five groups of mice gut using the Affymetrix Mouse Gene 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool. No techinical replicates were performed.