• In addition, C3G increased the protein expression of phosphorylated-AMPK/AMPK and Sirtuin 1 and decreased that of mitogen-activated protein kinases, such as phosphorylated-Akt/Akt and phosphorylated-ERK/ERK, thus demonstrating its neuroprotective effects. (biomedcentral.com)
  • Both cannabinoid receptors (CBRs) are, in fact, part of the heptahelical G protein-coupled receptor (GPCR) family and can inhibit adenyl cyclase activity or even stimulate mitogen-activated protein kinases (MAPKs), being, therefore, classified as Gi/0 receptors [ 3 - 5 ]. (irjournal.org)
  • ROS may induce intracellular calcium increase and subsequent contraction of PASMCs via direct or indirect interactions with protein kinases, phospholipases, sarcoplasmic calcium channels, transient receptor potential channels, voltage-dependent potassium channels and L-type calcium channels, whose relevance may vary under different experimental conditions. (ersjournals.com)
  • it is involved in skeletal muscle contraction, excitation-contraction coupling in cardiac and smooth muscle, and activation of protein kinases and enzyme phosphorylation. (msdmanuals.com)
  • MAPK is a mitogen-activated protein kinase, a class of protein kinases with dual phosphorylation of serine and tyrosine in the cytosol. (cusabio.com)
  • The ribosomal protein S6 kinase 1 (S6K1) is one of two mammalian p70-RSK proteins, acting as a downstream mediator of mammalian target of rapamycin (mTOR) in the phosphoinositide 3-kinase (PI3K) pathway and/or the Ras-MAPK pathway . (axonmedchem.com)
  • Since adenosine kinase has a lower K m and V max than adenosine deaminase, deamination plays a significant role only when cytosolic adenosine saturates the phosphorylation pathway. (nih.gov)
  • It is now well established that in order to translate into the appropriate cellular function multiple extracellular inputs, which may act simultaneously on the same cell, the cAMP/PKA signalling pathway is compartmentalised. (ox.ac.uk)
  • Similarly, cannabinoid preparations deactivate a promitogenic p42/p44 extracellular signal-regulated kinase pathway. (royalseedsboutique.com)
  • 18 These signal exchanges promote activation of some cellular pathways that are essential for DPC growth, function, and survival, such as the activation of Wnt signaling pathway. (benitonovas.com)
  • It has been reported that lung cancer cells exhibit upregulated expression of all key glycolytic enzymes [hexokinase 2 (HK2), phosphofructokinase and pyruvate kinase (PK)] ( 13 ), suggesting that the essential enzymes of the aerobic glycolytic pathway have a critical role in the development of lung carcinoma. (spandidos-publications.com)
  • SCARA5 expression is significantly downregulated in various tumor tissues including liver cancer (LC), rectal cancer, and glioblastoma [ 15 , 16 ] and might affect cell proliferation and invasion abilities by the focal adhesion kinase (FAK) signaling pathway and epithelial-mesenchymal transition (EMT) [ 5 , 17 - 20 ]. (hindawi.com)
  • The main process of this pathway: the growth factor activates the receptor by binding to the tyrosine kinase receptor, and the activated tyrosine kinase receptor activates the Ras protein, then the Ras protein phosphorylates the Raf, and the activated Raf phosphorylates the downstream MEK. (cusabio.com)
  • Inhibition of the p38 MARK pathway down-regulates the activity of protein kinase C ( PKC ), which plays an important role in osteogenic differentiation of cells. (cusabio.com)
  • This protein is a member of the G protein-coupled receptor (GPCR) family which possess seven transmembrane alpha helices, as well as an extracellular N-terminus and an intracellular C-terminus. (wikipedia.org)
  • Abundant extracellular adenosine can then bind to the A2A receptor resulting in a Gs-protein coupled response, resulting in the accumulation of intracellular cAMP, which functions primarily through protein kinase A to upregulate inhibitory cytokines such as transforming growth factor-beta (TGF-β) and inhibitory receptors (i.e. (wikipedia.org)
  • By preventing ADO phosphorylation, ADK inhibition increases intracellular ADO concentrations, altering the equilibrium of the bidirectional transport systems responsible for ADO reuptake with the net effect of increasing the local concentration of ADO in the extracellular compartment. (axonmedchem.com)
  • Selective compounds have been developed that target either the extracellular ligand-binding region of the EGFR (including a number of monoclonal antibodies [MAbs], immunotoxins, and ligand-binding cytotoxic agents) or the intracellular tyrosine kinase region (including various small-molecule inhibitors). (medscape.com)
  • Intracellular adenosine is rapidly metabolized either via phosphorylation to adenosine monophosphate by adenosine kinase, or via deamination to inosine by adenosine deaminase in the cytosol. (nih.gov)
  • As in somatic cells, sperm intracellular cAMP concentration is regulated by the opposite action of two enzymes: the adenylyl cyclases (AC), which synthesize cAMP from ATP, and the phosphodiesterases (PDE), which break the phosphodiester bond of cAMP to form 5'-adenosine monophosphate (AMP). (plos.org)
  • Similarly, hypoxia and inflammation may lead to reduced expression of adenosine kinase, which is believed to convert GS-441524 to GS-441524 monophosphate, the perceived rate-limiting step in the intracellular formation of GS-441524 triphosphate. (regionh.dk)
  • Moreover, increases in extracellular and intracellular levels of adenosine, which may occur during critical illnesses, has the potential to competitively decrease cellular uptake and phosphorylation of GS-441524. (regionh.dk)
  • MTX increases intracellular accumulation of adenosine monophosphate (AMP) and 5-aminoimidazole-4-carboxamide ribonucleotide which activates AMP-activated protein kinase (AMPK). (bmj.com)
  • Both extracellular and intracellular calcium concentrations are tightly regulated by bidirectional calcium transport across the plasma membrane of cells and intracellular organelles, such as the endoplasmic reticulum, the sarcoplasmic reticulum of muscle cells, and the mitochondria. (msdmanuals.com)
  • Calcium is also involved in the action of other intracellular messengers, such as cAMP (cyclic adenosine monophosphate) and inositol 1,4,5-triphosphate, and thus mediates the cellular response to numerous hormones, including epinephrine , glucagon , vasopressin (antidiuretic hormone), secretin, and cholecystokinin. (msdmanuals.com)
  • Adenosine monophosphate formed by phosphorylation of adenosine is incorporated into the high-energy phosphate pool. (nih.gov)
  • In mammals, adenosine 3', 5'-cyclic monophosphate (cAMP) is known to play highly important roles in sperm motility and acrosomal exocytosis. (plos.org)
  • Cyclic AMP (adenosine 3', 5'-cyclic monophosphate) is an important player in sperm function. (plos.org)
  • 3'-5'-Cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signalling is activated by different extracellular stimuli and mediates many diverse processes within the same cell. (ox.ac.uk)
  • IF affects hepatic autophagy through multiple interacting pathways and molecular mechanisms, including adenosine monophosphate (AMP)-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), silent mating-type information regulatory 2 homolog-1 (SIRT1), peroxisomal proliferator-activated receptor alpha (PPARα) and farnesoid X receptor (FXR), as well as signaling pathways and molecular mechanisms such as glucagon and fibroblast growth factor 21 (FGF21). (golearnweb.com)
  • Activation of chemomigration-related cell signaling (extracellular signal-regulated kinase (ERK), 5' adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC)) was evaluated by Western blot analysis. (unimi.it)
  • Keywords: Soluble adenylyl cyclase cAMP Microdomain Cancer Diagnostics 1 Introduction Cyclic adenosine monophosphate (cAMP) is one of the most ancient CDCL1 signaling molecules present from bacteria to man. (bioinf.org)
  • The HER (erbB) family of transmembrane receptor tyrosine kinases is one of the cytostatic targets in tumor cell growth and survival. (medscape.com)
  • In EPH-related tyrosine kinases, appears to mediate cell-cell initiated signal transduction via the binding of SH2-containing proteins to a conserved tyrosine that is phosphorylated. (embl.de)
  • The p70 ribosomal S6 kinases (S6K) and p90 ribosomal S6 kinases (RSK) are distinct families of Ser/Thr kinases (EC 2.7.11.1) that regulate diverse cellular processes by phosphorylation of ribosomal protein S6 (Rps6). (axonmedchem.com)
  • p90 ribosomal S6 kinase and p70 ribosomal S6 kinase link phosphorylation of the eukaryotic chaperonin containing TCP-1 to growth factor, insulin, and nutrient signaling. (axonmedchem.com)
  • Furthermore, EPO-induced neuroprotection as well as phosphorylation of the proapoptotic Bcl family member Bad was reduced by the phosphoinositide-3 kinase (PI3K) inhibitor LY294002. (jneurosci.org)
  • The actions of the A2A receptor are complicated by the fact that a variety of functional heteromers composed of a mixture of A2A subunits with subunits from other unrelated G-protein coupled receptors have been found in the brain, adding a further degree of complexity to the role of adenosine in modulation of neuronal activity. (wikipedia.org)
  • Heteromers consisting of adenosine A1/A2A, dopamine D2/A2A and D3/A2A, glutamate mGluR5/A2A and cannabinoid CB1/A2A have all been observed, as well as CB1/A2A/D2 heterotrimers, and the functional significance and endogenous role of these hybrid receptors is still only starting to be unravelled. (wikipedia.org)
  • Older research on adenosine receptor function, and non-selective adenosine receptor antagonists such as aminophylline, focused mainly on the role of adenosine receptors in the heart, and led to several randomized controlled trials using these receptor antagonists to treat bradyasystolic arrest. (wikipedia.org)
  • As a result, Adenosine receptor A2A decreases activity in the Dopamine D2 receptors. (wikipedia.org)
  • Therefore, smFRET has been limited to studies of inter-receptor interactions in cellular membranes and receptors in detergent environments. (nature.com)
  • Because FGF2 and P2 purinergic receptors are coupled to extracellular signal regulated protein kinase (ERK), a key member of a signaling cascade that regulates proliferation, we also investigated the role of ERK in regulating cyclin expression induced by FGF2 and ATP. (sagepub.com)
  • The levels of phosphorylated AMP-activated protein kinase (P-AMPK), well known for its role in cellular energy sensing and regulation, and ATP show reciprocal changes. (jneurosci.org)
  • Furthermore, the changes in ATP exhibit reciprocity with the phosphorylated state of the cellular energy sensor, phosphorylated AMP-activated protein kinase (P-AMPK), thus supporting the induction of anabolic processes during sleep. (jneurosci.org)
  • Adenosine (ADO) is an endogenous homeostatic inhibitory neuromodulator that reduces cellular excitability at sites of tissue injury and inflammation. (axonmedchem.com)
  • Adenosine is an endogenous nucleoside occurring in all cells of the body. (nih.gov)
  • GPCRs recognize a large variety of endogenous extracellular signaling molecules transmitting their corresponding signals inside the cell, and this process can be modulated by synthetic ligands or drug molecules. (nature.com)
  • Adenosine triphosphate (ATP), mainly produced in mitochondria, plays an important role in various pathological processes such as inflammation and acute liver injury. (bvsalud.org)
  • ABT-702 (4-amino-5-(3-bromophenyl)-7-(6-morpholinopyridin-3-yl)pyrido[2, 3-d]pyrimidine), a novel orally effective adenosine kinase inhibitor with analgesic and anti-inflammatory. (axonmedchem.com)
  • Discovery of 4-amino-5-(3-bromophenyl)-7-(6-morpholino-pyridin-3-yl)pyrido[2,3-d]pyrimidine, an orally active, non-nucleoside adenosine kinase inhibitor. (axonmedchem.com)
  • Cultured neurons express EpoR, and the Janus kinase-2 (JAK-2) inhibitor AG490 abolished EPO-induced tolerance against OGD. (jneurosci.org)
  • Emerging evidence shows that key signal transduction pathways including TGFβ (transforming growth factor-β), ERK (extracellular signal-regulated kinase), and mTORC1 (mechanistic target of rapamycin complex 1) regulate downstream gene expression through m 6 A processing. (molcells.org)
  • In this review, we will focus on how the signal transduction pathways, which play key roles in diverse physiological and pathological conditions, coordinate cellular processes through m 6 A. Given that m 6 A also controls signaling pathways through RNA modification or acting as a ligand, understanding the crosstalk between signal transduction networks and m 6 A RNA processing will provide us insights into the complex biological systems. (molcells.org)
  • By influencing the metabolism of energy and oxygen radicals as well as cellular stress response systems, IF protects hepatocytes from genetic and environmental factors. (golearnweb.com)
  • Iron represents a micronutrient for cellular metabolism and aerobic respiration, but cellular iron overload produces toxic build-up in many organs (including brain) via free radical formation. (unimi.it)
  • cAMP microdomains were first appreciated in the 1970s from the groups of Keely Hayes Brunton and others when they identified that different tmAC activating hormones (e.g. β-adrenergic receptor and prostaglandin E1 agonists) all led to cAMP elevation but each induced unique cellular events in cardiomyocytes e.g. only β-adrenergic activation induced improved contractility and glycogen rate of metabolism [12]. (bioinf.org)
  • Currently, there are 4 known MAPK signaling pathways, including the extracellular signal-regulated kinase ( ERK ), c- Jun N-terminal kinase (JNK, also known as SAPK), p38 and ERK5 pathways. (cusabio.com)
  • The c-Jun N-terminal kinase (JNK), also known as stress-activated protein kinase (SAPK), is another subclass of MAPK in mammals. (cusabio.com)
  • p38 MAPK can be activated by a variety of extracellular stress responses, including ultraviolet, radiation and proinflammatory factors. (cusabio.com)
  • Adenosine is antagonized competitively by methylxanthines such as caffeine and theophylline, and potentiated by blockers of nucleoside transport such as dipyridamole. (nih.gov)
  • GS-441524 is an adenosine analog and the parent nucleoside of the prodrug remdesivir, which has received emergency approval for treatment of COVID-19. (regionh.dk)
  • Intravenously administered adenosine is rapidly cleared from the circulation via cellular uptake, primarily by erythrocytes and vascular endothelial cells. (nih.gov)
  • While extracellular adenosine is primarily cleared by cellular uptake with a half-life of less than 10 seconds in whole blood, excessive amounts may be deaminated by an ecto-form of adenosine deaminase. (nih.gov)
  • Importantly, cellular uptake of GS-441524 may be reduced during hypoxia and inflammation due to decreased expression of adenosine transporters. (regionh.dk)
  • It also inhibits cellular adenosine uptake. (royalseedsboutique.com)
  • When larger doses are given by infusion, adenosine decreases blood pressure by decreasing peripheral resistance. (nih.gov)
  • Inducing sleep and delta activity by adenosine infusion into basal forebrain during the normally active dark period also increases ATP. (jneurosci.org)
  • Sperm cells are highly sensitive to reactive oxygen species (ROS), which are produced during cellular oxidation. (mdpi.com)
  • Inosine formed by deamination of adenosine can leave the cell intact or can be degraded to hypoxanthine, xanthine, and ultimately uric acid. (nih.gov)
  • The crystallographic structure of the adenosine A2A receptor reveals a ligand binding pocket distinct from that of other structurally determined GPCRs (i.e., the beta-2 adrenergic receptor and rhodopsin). (wikipedia.org)
  • More importantly, IF can activate hepatic autophagy, which is important for maintaining cellular homeostasis and energy balance, quality control, cell and tissue remodeling, and defense against extracellular damage and pathogens. (golearnweb.com)
  • Extracellular adenosine gathers in response to cellular stress and breakdown through interactions with hypoxia induced HIF-1α. (wikipedia.org)
  • Hypoxia may be particularly critical to the ability of GS-441524 to eliminate SARS-CoV-2 from tissues with low basal expression of adenosine transporters, such as alveolar cells. (regionh.dk)
  • Here, we performed smFRET experiments on functionally active human A 2A adenosine receptor (A 2A AR) molecules embedded in freely diffusing lipid nanodiscs to study their intramolecular conformational dynamics. (nature.com)
  • IF involves a series of coordinated metabolic and hormonal changes to maintain the organism's metabolic balance and cellular homeostasis. (golearnweb.com)
  • As adenosine requires no hepatic or renal function for its activation or inactivation, hepatic and renal failure would not be expected to alter its effectiveness or tolerability. (nih.gov)
  • Shi, You-Fang 2005-12-03 00:00:00 Extracellular ATP enhances the mitogenic activity of fibroblast growth factor-2 (FGF2) in astrocytes, but the molecular mechanism underlying this synergistic interaction is not known. (sagepub.com)
  • To determine whether the potentiating effect of extracellular ATP involves cell cycle control mechanisms, we have measured the expression of cyclins that are induced in different phases of the cell cycle in primary cultures of rat cortical astrocytes. (sagepub.com)
  • ACs 1-9 encode for proteins with a fairly similar structure in that all of them are transmembrane proteins (tmACs) and reside principally at the plasma membrane and endosomes making these ACs well suited to respond to extracellular signals. (bioinf.org)
  • This ATP-delta correlation is also confirmed by pharmacologically induced sleep using adenosine perfusion into the basal forebrain. (jneurosci.org)
  • In mammals cAMP controls a wide range of cellular processes and is present in every cell type and organ. (bioinf.org)
  • Available protein expression data suggest that several adenosine transporters are expressed at only low levels in the epithelial cells lining the alveoli in the lungs, i.e., the alveolar cells or pneumocytes from healthy lungs. (regionh.dk)
  • 2 EndMT is a process by which endothelial cells lose a portion of their cellular features and obtain the mesenchymal phenotype, including the loss of tight junctions and increased production of extracellular matrix. (dovepress.com)
  • Cellular senescence , the process by which damaged cells terminate normal growth and reproduction cycles to prevent injured cells from proliferating. (foundmyfitness.com)
  • while p38 kinase inhibited cell develop into ectodermal cells and eventually differentiate into neural cells. (cusabio.com)
  • m 6 A recruits effector proteins that determine the fate of mRNAs through changes in splicing, cellular localization, stability, and translation efficiency. (molcells.org)
  • In the following sections we will review the part of exchange protein triggered by cAMP protein kinase A and A kinase anchoring proteins in cAMP signaling and how investigations of each have contributed to our understanding of cAMP microdomains. (bioinf.org)
  • The mitogen-activated protein (MAP) kinase cascade can either stimulate or inhibit DNA synthesis in primary cultures of rat hepatocytes depending upon whether its activation is acute/phasic or chronic. (sagepub.com)
  • Upon vascular injury, platelets are exposed to the subendothelium, and several agonists, including adenosine diphosphate (ADP) and thrombin, are generated at the injury site, which can stimulate platelet adhesion, activation and aggregation. (spandidos-publications.com)
  • [3] Cellular checkpoints and DNA damage-response pathways help preserve genomic stability and cell-cycle progression, but these processes decline with aging. (foundmyfitness.com)
  • It is involved in flagellar movements and motility, and in cellular events that occur in the sperm head, that will lead to successful interaction with the egg and to fertilization [ 1 , 2 ]. (plos.org)
  • In order to overcome these limitations, this study explored the possibility to use cancer cell derived extracellular vesicles (EVs) as drug delivery system for oncolytic adenovirus. (helsinki.fi)
  • The GDNF family ligands (GFLs) function through a glycosyl-phosphatidylinositol-(GPI) anchored coreceptor, GDNF family receptor alpha (GFRα), and rearranged during transfection (RET), a well-known receptor tyrosine kinase involved in kidney development, spermatogonial stem cell maintenance, and the development and maintenance of the sympathetic, parasympathetic, and enteric nervous systems [ 1 , 2 ]. (medsci.org)
  • 2 Anderson R, Lukey P T. A biological role for ascorbate in the selective neutralization of extracellular phagocyte-derived oxidants. (thieme-connect.com)
  • These adenosine studies prompted us to examine the actual "currency of brain cellular energy" ATP, since adenosine may be an indicator of neuronal activity-dependent energy use, by reflecting ATP breakdown. (jneurosci.org)
  • The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, and also denotes the human gene encoding it. (wikipedia.org)
  • MEK can phosphorylate and activate ERK, which is transferred into the nucleus and regulates gene expression by activating other kinases or transcription factors. (cusabio.com)
  • Like a pH and metabolic sensor sAC is definitely poised to function as an intrinsic sensor of cellular health. (bioinf.org)
  • In our previous study, several compounds extracted from this herb, including luteolin‑4'‑O‑β‑D‑glucopyranoside (LGP), were revealed to exert inhibitory effects on adenosine diphosphate (ADP)‑induced platelet aggregation. (spandidos-publications.com)
  • The RSK family of kinases: emerging roles in cellular signaling. (axonmedchem.com)
  • About 1% of bone calcium is freely exchangeable with the extracellular fluid and, therefore, is available for buffering changes in calcium balance. (msdmanuals.com)
  • Immediately on completion of the race transient elevations occurred in the concentrations of circulating neutrophils, monocytes and platelets, IL-6, cortisol, CRP, and creatine kinase in both groups. (thieme-connect.com)
  • The intravenous bolus dose of 6 or 12 mg adenosine usually has no systemic hemodynamic effects. (nih.gov)
  • A cumulative 60% of patients with paroxysmal supraventricular tachycardia had converted to normal sinus rhythm within one minute after an intravenous bolus dose of 6 mg adenosine (some converted on 3 mg and failures were given 6 mg), and a cumulative 92% converted after a bolus dose of 12 mg. (nih.gov)
  • The recommended adenosine injection dose is 0.14 mg/kg/min infused over six minutes (total dose of 0.84 mg/kg) ( Table 1 ). (pfizermedicalinformation.com)