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Journal of Chromatography. B,... Oct 2022RNA modifications have been revealed to be essential in many biological activities, and their disorders are associated with various human diseases, including cancers....
Determination of adenosine and its modifications in urine and plasma from breast cancer patients by hydrophilic interaction liquid chromatography-tandem mass spectrometry.
RNA modifications have been revealed to be essential in many biological activities, and their disorders are associated with various human diseases, including cancers. 2'-O-methyladenosine (A), N-methyladenosine (mA), N-methyladenosine (mA), N,2'-O-dimethyladenosine (mA) and N,N-dimethyladenosine (mA) are important adenosine (A) modifications. The noninvasive collection of urine samples and the diverse contents of metabolites in plasma make them favored biofluids for biomarkers discovery. In this work, we established a hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method to quantify these six nucleosides in urine and plasma of healthy controls and breast cancer (BC) patients. The limit of detection (LOD) for A, A, mA, mA, mA, and mA were 0.0025, 0.01, 0.05, 0.005, 0.005, and 0.005 nM. The results showed that the concentrations of A, mA, and mA were increased, whereas mA was decreased in the urine of BC patients compared with the healthy controls. We also found that the level ratios of mA/A, mA/A, and mA/A were all reduced in plasma from BC patients, compared with healthy controls. Interestingly, these ratios of methylated adenosine nucleosides to adenosine in plasma could better discriminate BC patients from healthy controls, compared to the levels of these nucleosides. The present study not only suggests these modified adenosines can act as noninvasive biomarkers of BC but also will contribute to investigating the impacts of RNA methylation on the occurrence and development of BC.
Topics: Adenosine; Breast Neoplasms; Chromatography, Liquid; Female; Humans; Hydrophobic and Hydrophilic Interactions; Nucleosides; RNA; Tandem Mass Spectrometry
PubMed: 36041348
DOI: 10.1016/j.jchromb.2022.123428 -
Cell Jan 2005We predict regulatory targets of vertebrate microRNAs (miRNAs) by identifying mRNAs with conserved complementarity to the seed (nucleotides 2-7) of the miRNA. An...
We predict regulatory targets of vertebrate microRNAs (miRNAs) by identifying mRNAs with conserved complementarity to the seed (nucleotides 2-7) of the miRNA. An overrepresentation of conserved adenosines flanking the seed complementary sites in mRNAs indicates that primary sequence determinants can supplement base pairing to specify miRNA target recognition. In a four-genome analysis of 3' UTRs, approximately 13,000 regulatory relationships were detected above the estimate of false-positive predictions, thereby implicating as miRNA targets more than 5300 human genes, which represented 30% of our gene set. Targeting was also detected in open reading frames. In sum, well over one third of human genes appear to be conserved miRNA targets.
Topics: 3' Untranslated Regions; Adenosine; Amino Acid Sequence; Animals; Chickens; Dogs; Gene Expression Regulation; Gene Targeting; Humans; Mice; MicroRNAs; Molecular Sequence Data; Nucleic Acid Hybridization; Nucleotides; RNA, Messenger; Rats
PubMed: 15652477
DOI: 10.1016/j.cell.2004.12.035 -
Nature Structural & Molecular Biology Feb 2016N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA. Recent discoveries of the locations, functions and mechanisms of m6A have shed...
N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA. Recent discoveries of the locations, functions and mechanisms of m6A have shed light on a new layer of gene regulation at the RNA level, giving rise to the field of m6A epitranscriptomics. In this Perspective, we provide an update on the various effects of mammalian m6A modification, which affects many different stages of the RNA life cycle.
Topics: Adenosine; Animals; Epigenesis, Genetic; Humans; Nucleic Acid Conformation; Protein Biosynthesis; RNA; Transcriptome
PubMed: 26840897
DOI: 10.1038/nsmb.3162 -
Hospital Practice (Office Ed.) Mar 1993An important regulator of cardiac rhythm and coronary blood flow, adenosine is finding valuable applications in treatment and diagnosis. It should soon be available for... (Review)
Review
An important regulator of cardiac rhythm and coronary blood flow, adenosine is finding valuable applications in treatment and diagnosis. It should soon be available for cardiac imaging and eventually as a protective agent against acute myocardial infarction and reperfusion injury. Study of adenosine's uses is providing insights into its biologic effects in a variety of organ systems.
Topics: Adenosine; Animals; Blood Flow Velocity; Calcium Channels; Clinical Trials as Topic; Coronary Vessels; Diagnosis, Differential; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Exercise Test; Heart Rate; Hemodynamics; Humans; Potassium Channels; Receptors, Purinergic; Signal Transduction; Tachycardia, Paroxysmal; Tachycardia, Supraventricular
PubMed: 8383138
DOI: 10.1080/21548331.1993.11442765 -
The American Journal of Physiology Mar 1985In anesthetized cats, reduction of portal flow by occlusion of the superior mesenteric artery results in rapid increase in hepatic arterial (HA) flow that compensates...
In anesthetized cats, reduction of portal flow by occlusion of the superior mesenteric artery results in rapid increase in hepatic arterial (HA) flow that compensates for (buffers) 25.5 +/- 2.7% of the decreased portal flow. The hypothesis tested is that adenosine concentration produced near the HA resistance vessels is regulated by washout into portal vessels in intimate contact with the HA. Reduced portal flow leads to accumulation of adenosine and HA dilation. Several criteria for this hypothesis are met. First, adenosine is a potent dilator of the HA. Second, portal blood has access to HA resistance vessels as shown by a marked dilator effect of adenosine infused into the portal vein; it is therefore possible for adenosine produced locally to diffuse into portal blood. Third, dipyridamole potentiated the dilator response to adenosine as well as potentiating the buffer response from a 23% compensation for reduced portal flow to 34%. Fourth, 1-methyl-3-isobutylxanthine (MIX) antagonized exogenous adenosine and reduced the buffer response from 19% down to 5%. These data strongly support the hypothesis that the hepatic arterial buffer response is mediated by local concentrations of adenosine that are controlled by the rate of washout into portal blood.
Topics: 1-Methyl-3-isobutylxanthine; 2-Chloroadenosine; Adenosine; Animals; Blood Pressure; Cats; Dipyridamole; Hepatic Artery; Liver Circulation; Portal System; Rheology; Time Factors; Vasodilation
PubMed: 2579585
DOI: 10.1152/ajpheart.1985.248.3.H331 -
The Journal of Surgical Research Nov 1994During induced ischemia for cardiac surgery, nucleotides are degraded while being used to maintain myocyte integrity. The resulting nucleosides washout upon reperfusion,...
During induced ischemia for cardiac surgery, nucleotides are degraded while being used to maintain myocyte integrity. The resulting nucleosides washout upon reperfusion, limiting nucleotide resynthesis resulting in poor postischemic cardiac function. We studied if the mechanism of the beneficial effect of adenosine, a nucleotide precursor, which is known to improve postischemic functional recovery is as a substrate for nucleotide resynthesis or by stimulation of adenosine A1 or A2 receptors. Isolated, retrograde-perfused rabbit hearts received cardioplegia as controls or cardioplegia containing 80 microM [R]-N6-[1-methyl-2-phenylethyl]-adenosine, an A1 receptor agonist, or 200 microM 5'-(N-ethylcarboxamido)adenosine, or 200 microM adenosine alone. To assess functional recovery developed pressure, max dP/dt, pressure-rate product, coronary flow, and myocardial oxygen consumption were compared after 120 min of 34 degrees C global cardioplegic ischemia. Following ischemia and reperfusion, adenosine alone had better developed pressure, dP/dt, and pressure-rate product, while heart rates, wet weights, %H2O, end-diastolic volumes/pressures, and oxygen extraction were not significantly different between groups. While adenosine receptor stimulation may play a role, in this model the beneficial effect of adenosine on functional recovery appears to be mediated more by adenosine's role as a substrate for nucleotide resynthesis.
Topics: Adenosine; Animals; Cardioplegic Solutions; Female; Heart; Heart Arrest, Induced; Heart Rate; Male; Myocardial Reperfusion Injury; Oxygen Consumption; Rabbits; Receptors, Purinergic P1; Regional Blood Flow; Signal Transduction; Substrate Specificity; Vasodilator Agents
PubMed: 7967597
DOI: 10.1006/jsre.1994.1188 -
Expert Opinion on Investigational Drugs Feb 2007Oral antiplatelet therapy with P2Y(12) receptor blockers (especially clopidogrel) is the current choice of treatment during acute coronary syndromes and percutaneous... (Review)
Review
Oral antiplatelet therapy with P2Y(12) receptor blockers (especially clopidogrel) is the current choice of treatment during acute coronary syndromes and percutaneous interventions. To address the various limitations of thienopyridine therapy (including response variability and non-responsiveness) a novel drug, AZD6140, is under clinical development. AZD6140 is an oral and reversible P2Y(12) receptor blocker that does not require hepatic conversion to an active metabolite and produces an overall superior ADP-induced platelet inhibition with less response variability than clopidogrel. It has fast onset and offset actions that may be advantageous in patients who may have to undergo immediate surgery.
Topics: Adenosine; Animals; Coronary Disease; Drugs, Investigational; Humans; Platelet Aggregation Inhibitors; Purinergic P2 Receptor Antagonists; Ticagrelor
PubMed: 17243942
DOI: 10.1517/13543784.16.2.225 -
Clinical Pharmacy Apr 1990
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Thrombosis Research Jan 2002Adenosine is an endogenous antiaggregating substance that influences the platelet responses through specific A-type receptors that activate adenylate cyclase increasing...
Adenosine is an endogenous antiaggregating substance that influences the platelet responses through specific A-type receptors that activate adenylate cyclase increasing the levels of 3',5'-cyclic adenosine monophosphate (cAMP). In this study, we investigated whether adenosine can also influence the levels of 3',5'-cyclic guanosine monophosphate (cGMP) and decrease the aggregating response of human platelets to adenosine-5-diphosphate (ADP) through this nucleotide. In platelet samples from healthy volunteers, we evaluated the effect of adenosine on ADP-induced aggregation and cyclic nucleotide synthesis. Some experiments were repeated in the presence of dipyridamole (inhibitor of adenosine uptake and phosphodiesterase activity), N(G)-monomethyl-L-arginine (L-NMMA, nitric synthase inhibitor), ionomycin (calcium ionophore), and ambroxol (2-amino-3,5-dibromo-N-[trans-4-hydroxycyclohexyl]benzylamine, inhibitor of nitric oxide (NO)-dependent activation of guanylate cyclase). Adenosine decreased the response to ADP in a concentration-dependent way (analysis of variance, ANOVA: P<.0001): cAMP levels increased from 30.0 +/- 2.0 (control) to 46.0 +/- 3.0 pmol/10(9) platelets (in the presence of 15 mumol/l adenosine) and cGMP levels increased from 5.6 +/- 1.0 (control) to 10.9 +/- 2.0 pmol/10(9) platelets (in the presence of 15 mumol/l adenosine). Also, nucleotide levels measured at the end of aggregation were higher in platelet samples exposed to adenosine than in controls. Dipyridamole at 40 mumol/l slightly increased adenosine's effects on both nucleotides. L-NMMA blunted the effect of adenosine on cGMP both in unstimulated samples and in aggregated platelets without any effect on cAMP synthesis. Platelet exposure to L-NMMA and ambroxol partially prevented adenosine's effect on ADP-induced aggregation. In conclusion, adenosine, which enhances intraplatelet cAMP levels, was determined to also cause an increase in cGMP concentrations through a mechanism that involves NO synthesis. This effect plays a direct role in the adenosine-induced antiaggregation.
Topics: Adenosine; Adenosine Diphosphate; Blood Platelets; Cyclic GMP; Dose-Response Relationship, Drug; Drug Antagonism; Guanylate Cyclase; Humans; Nitric Oxide; Platelet Aggregation; Platelet Aggregation Inhibitors
PubMed: 11864710
DOI: 10.1016/s0049-3848(01)00412-1 -
Brain Research Jan 1989Administration of adenosine and agonists of the adenosine receptors to rats results in hypoactivity, hypothermia, muscle relaxation and antinociception. In the present...
Administration of adenosine and agonists of the adenosine receptors to rats results in hypoactivity, hypothermia, muscle relaxation and antinociception. In the present study, we found that the adenosine ligand, N6-R-phenylisopropyladenosine (R-PIA), increased food intake in rats at a time in the day when rats normally eat very little food or none at all. Feeding was not reliably stimulated upon the first exposure to R-PIA, but was clearly increased following repeated administration of this agonist. Other adenosine agonists, namely 2-chloradenosine and 5'N-ethylcarboxamide adenosine, failed to alter feeding after a single injection or after repeated exposure. The adenosine antagonist, caffeine, did not block R-PIA's effect on food intake, whereas the opioid antagonist, naloxone, blocked R-PIA-induced eating. These data suggest that R-PIA stimulates feeding independent of the A1 or A2 adenosine receptors.
Topics: 2-Chloroadenosine; Adenosine; Adenosine-5'-(N-ethylcarboxamide); Animals; Feeding Behavior; Grooming; Male; Motor Activity; Phenylisopropyladenosine; Rats; Rats, Inbred Strains; Reference Values
PubMed: 2702488
DOI: 10.1016/0006-8993(89)91415-7