OrganismsChemicals and DrugsPhenomena and Processes
CyclosporinsMitosporic FungiCyclosporineDrug Resistance
CyclophilinCalcineurinCyclophilinsImmunosuppressant cyclosporinLipidsImmunosuppressive AgentsMicrobial productsMitochondrialInhibitorsInhibitionFK506Peptidyl-prolyl cTacrolimusInhibitorExtracellularPermeabilityMetabolismKinaseAlbuminAmino AcidsAnionPPIaseGenesTurnoverGeneTherapeuticViralTransporterMethotrexateEnzymeImmune systemCYP3A4MechanismTargetsSubstratesToxicEndoplasmic reticulumMolecularConcentrationDrugPurificationVitroDiseasesProcessesFactorIncludeFoundSpecificFamilies
Cyclophilin5
  • Classical 'first-generation' inhibitors of the mPTP, such as cyclosporin A, inhibit cyclophilin D (CypD), a protein that is believed to regulate the pore. (globenewswire.com)
  • The first type of this enzyme found proved to be the protein cyclophilin, which binds the immunosuppressant cyclosporin A. (cathdb.info)
  • Two protein-protein interaction sites on the spliceosome-associated human cyclophilin CypH. (nih.gov)
  • Studies aimed to unfold the site of CSA action have shown that this molecule binds to cytosolic proteins of the cyclophilin family. (hal.science)
  • The principal cyclosporin A and tacrolimus binding proteins cyclophilin A and FKBP12 were also expressed by keratinocytes and nonimmune cells in skin. (ncl.ac.uk)
Calcineurin7
  • The DNA binding, active NF-AT complex contains a cytoplasmic, Ca2+/calcineurin dependent, cyclosporin sensitive subunit, designated NF-ATc, which is present in the cytoplasm of resting cells. (bdbiosciences.com)
  • P-sites 2 and 3 phosphorylated by Ca2+ calmodulin-dependent protein kinase II) were excellent substrates for protein phosphatase 2A, whereas P-sites 4, 5, and 6 (phosphorylated by mitogen-activated protein kinase) were efficiently dephosphorylated only by Ca2+-calmodulin-dependent protein phosphatase 2B-calcineurin. (ucl.ac.uk)
  • Inhibition of calcineurin activity by cyclosporin A resulted in a complete block of Ca2+-dependent dephosphorylation of P-sites 4, 5, and 6 and correlated with a prominent increase in ionomycin-evoked glutamate release. (ucl.ac.uk)
  • Cyclosporin A and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor nuclear factor of activated T cells (NFAT). (ncl.ac.uk)
  • We investigated whether nonimmune cells in human skin express calcineurin and NFAT1 and whether cyclosporin A and tacrolimus block activation of calcineurin/NFAT in epidermal keratinocytes. (ncl.ac.uk)
  • We assessed calcineurin/NFAT activation in cultured keratinocytes by measuring the degree of nuclear localization of calcineurin and NFAT1 using immunofluorescence/confocal microscopy and assessed if cyclosporin A and tacrolimus blocked nuclear translocation of these proteins. (ncl.ac.uk)
  • Agonists that induce keratinocyte differentiation, specifically 12:0-tetradecanoyl-phorbol-13-acetate (TPA) plus ionomycin, TPA, and raised extracellular calcium, induced nuclear translocation of NFAT1 and calcineurin in keratinocytes that was inhibited by pretreatment with cyclosporin A or tacrolimus. (ncl.ac.uk)
Cyclophilins3
  • Influences of cyclosporin A and non-immunosuppressive derivatives on cellular cyclophilins and viral nucleocapsid protein during human coronavirus 229E replication. (uni-muenchen.de)
  • A comparison of their known functions has identified, besides a common role within protein folding, multiple roles for the cyclophilins within pre-mRNA splicing and cellular signalling, and within transcription and cell cycle regulation for the parvulins. (biomedcentral.com)
  • The peptidyl-prolyl cis / trans isomerase (PPIase) class of proteins is traditionally comprised of three distinct protein families, the cyclophilins (cyclosporin A binding proteins), FKBPs (FK506 binding proteins) and parvulins, that are linked by their shared ability to catalyse the bond preceding a proline residue between its cis and trans forms. (biomedcentral.com)
Immunosuppressant cyclosporin2
  • In clinical trials, a significant interaction between the endothelin receptor antagonist bosentan and the immunosuppressant cyclosporin A was observed, which could not be rationalized in terms of inhibition of drug-metabolizing enzymes. (aspetjournals.org)
  • During the clinical development of bosentan, the potential interaction between bosentan (500 mg b.i.d.) with the immunosuppressant cyclosporin A (300 mg b.i.d.) has been investigated in healthy male volunteers. (aspetjournals.org)
Lipids2
  • The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. (sigmaaldrich.com)
  • Both methods yield antibody in solution that is free of most other soluble proteins, lipids, etc. (bdbiosciences.com)
Immunosuppressive Agents1
  • The microbial products cyclosporin A (CsA), FK506 and rapamycin are potent immunosuppressive agents. (ox.ac.uk)
Microbial products1
  • [ 1 ] Neutrophils move to the site of invasion by means of chemotaxis, which occurs in response to microbial products, activated complement proteins, and cytokines. (medscape.com)
Mitochondrial5
  • The work will determine whether genetic deletion of this mitochondrial protein in vitro and in vivo protects brain cells , and therefore, whether drug modulation of this protein has the potential to improve Parkinson's symptoms. (globenewswire.com)
  • Cyclosporin A, given as a single-dose intrathecal bolus, has previously been shown to attenuate mitochondrial damage and reduce axonal injury in experimental TBI. (usuhs.edu)
  • The PKCδ inhibition and neuroprotection mediated by GRe were comparable to those by the ROS inhibitor N-acetylcysteine, the mitochondrial protectant cyclosporin A, the microglial inhibitor minocycline, or the PKCδ inhibitor rottlerin. (medworm.com)
  • Here, polymerase-interacting protein 2 (Poldip 2) was found in the endothelial mitochondrial matrix and no effects on Poldip 2 and NADPH oxidase 4 (NOX 4) expression treated by Ang II. (bvsalud.org)
  • Our previous study suggested a crosstalk between extracellular regulated protein kinase (ERK) phosphorylation and CypD expression, and gallic acid (GA) inhibited mitochondrial dysfunction in neurons depending on regulating the ERK-CypD axis. (bvsalud.org)
Inhibitors1
  • cyclosporin A, verapamil) are limited by their toxicity, whereas secondgeneration inhibitors (eg. (ac.rs)
Inhibition4
  • Results from both series of experiments point to inhibition of active bosentan uptake into the liver by cyclosporin A as the major underlying mechanism for this pharmacokinetic interaction that is in line with reports on other oatp-transported drugs. (aspetjournals.org)
  • The interaction between bosentan and cyclosporin A is a rare example of a pharmacokinetic interaction, which can mostly be attributed to the inhibition of transport processes in the liver. (aspetjournals.org)
  • It is, however, clear that inhibition of CYP3A4-mediated metabolism by cyclosporin A alone is insufficient to explain the increased bosentan concentrations and that inhibition of hepatocellular uptake offers an attractive mechanistic alternative also in human. (aspetjournals.org)
  • Inhibition of this pathway in epidermal keratinocytes may account, in part, for the therapeutic effect of cyclosporin A and tacrolimus in skin diseases such as psoriasis. (ncl.ac.uk)
FK5061
  • Cyclosporin A and FK506: molecular mechanisms of immunosuppression and probes for transplantation biology. (ox.ac.uk)
Peptidyl-prolyl c2
  • The peptidyl-prolyl cis / trans isomerase (PPIase) class of proteins is present in all known eukaryotes, prokaryotes, and archaea, and it is comprised of three member families that share the ability to catalyze the cis / trans isomerisation of a prolyl bond. (biomedcentral.com)
  • The protein encoded by this gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. (nih.gov)
Tacrolimus2
  • It is unnecessary to proactively reduce the dose of cyclosporin or tacrolimus when comedicated with LVX. (dovepress.com)
  • Systemic cyclosporin A and tacrolimus are effective treatments for psoriasis. (ncl.ac.uk)
Inhibitor1
  • These characteristics were used to develop an assay for antiviral compound screening in 96-well format, which was used to identify cyclosporin A as an inhibitor of MERS-CoV replication in cell culture. (microbiologyresearch.org)
Extracellular1
  • The -tocopherol regulates many genes expression, including extracellular proteins and inflammation modulators. (usp.br)
Permeability2
  • Several molecular changes in epithelial cells have been shown to yield protein-losing enteropathy by increasing the permeability to serum proteins. (medscape.com)
  • [ 5 ] In addition, infants and children with various forms of congenital glycosylation defects, another potential mechanism for loss of heparin sulfate proteoglycans, also have protein-losing enteropathy secondary to increased intestinal permeability. (medscape.com)
Metabolism2
  • We conclude that CYP3A4 is the major enzyme involved in the oxidative metabolism of cyclosporin G in human liver. (nih.gov)
  • This enzyme is involved in the metabolism of approximately half the drugs which are are used today, including acetaminophen, codeine, cyclosporin A, diazepam and erythromycin. (sigmaaldrich.com)
Kinase1
  • As L-type Ca2+ channels are thought to be targets of protein kinase C (PKC), we investigated the role of PKC under excitotoxic conditions. (medworm.com)
Albumin2
  • One potential clue is that renal losses of protein are usually limited to smaller proteins such as albumin, whereas the GI tract and skin losses are less discriminating. (medscape.com)
  • This results in the stasis of lymph and, if the pressure is high enough, the loss of lymphatic fluid rich in albumin and other proteins from the lacteals in intestinal microvilli into the lumen of the GI tract. (medscape.com)
Amino Acids1
Anion3
  • Both drugs reduced in a concentration-dependent manner the transport of fluorescein on the classical organic anion system and transport of fluorescein-methotrexate on multidrug resistance-associated protein 2 (Mrp2). (aspetjournals.org)
  • In vitro, the majority of bosentan uptake into liver cells was shown to depend on active transport and to be efficiently inhibited by cyclosporin A. All known members of the organic anion transporting polypeptide (oatp) transport protein family expressed in rat liver, i.e., oatp1, oatp2, and oatp4, were shown to be involved in the uptake of bosentan. (aspetjournals.org)
  • Transporters such as organic anion-transporting polypeptide 1A2, P-glycoprotein, human organic cation transporter 1, and multidrug and toxin extrusion protein 1 are involved in the pharmacokinetics of LVX. (dovepress.com)
PPIase1
  • This protein has been shown to possess PPIase activity and may act as a protein chaperone that mediates the interactions between different proteins inside the spliceosome. (nih.gov)
Genes1
  • These proteins are differentially expressed in tissues, suggesting that each may activate distinct sets of genes. (bdbiosciences.com)
Turnover2
  • This approach 'sticks' proteins of interests to E3 ubiquitin ligases of the ubiquitin-proteasome pathway, which helps with protein turnover and removes excess or damaged proteins within the body. (cas.org)
  • In 1949, Albright et al demonstrated an increase in protein turnover in patients with protein-losing enteropathy. (medscape.com)
Gene2
  • This study was aimed to evaluate the vitamin E supplementation effect on pancreatic gene expression of inflammatory markers in rats with alcoholic chronic pancreatitis induced by liquid diet containing ethanol (with or without -tocopherol supplementation), cyclosporin A and cerulein through the quantitative real time PCR technique. (usp.br)
  • New aspects of cyclosporin a mode of action: from gene silencing to gene up-regulation. (hal.science)
Therapeutic3
  • Cyclosporin A has emerged as a promising therapeutic agent in traumatic brain injury (TBI), although its precise neuroprotective mechanism is unclear. (usuhs.edu)
  • Intravenous administration produced therapeutic levels of cyclosporin A in brain parenchyma. (usuhs.edu)
  • Intravenous cyclosporin A administration achieves therapeutic levers in brain parenchyma and 10 mg/kg is the most effective dose in attenuating axonal damage after traumatic brain injury. (usuhs.edu)
Viral1
Transporter1
  • valspodar, biricodar) showed reduced toxicity but were confounded by unpredictable pharmacokinetic interactions with anticancer drugs as well as interactions with other transporter proteins. (ac.rs)
Methotrexate1
  • Graft-versus-host disease (GvHD) prophylaxis consisted of a short course of methotrexate and cyclosporin A. Neutrophil and platelet engraftment occurred on days 22 and 65 after surgery, respectively. (cdc.gov)
Enzyme1
  • Other distinct families of the enzyme exist, one being FK-506 binding proteins (FKBP) and another that includes parvulin from Escherichia coli. (cathdb.info)
Immune system1
  • A family of peptidyl-prolyl cis-trans isomerases that bind to CYCLOSPORINS and regulate the IMMUNE SYSTEM. (musc.edu)
CYP3A42
  • 6) in human hepatocytes in culture, pretreatment of cells with rifampicin and phenobarbital, 2 inducers of CYP3A4, produced a great increase in cyclosporin G oxidase activity, while beta-naphthoflavone, an inducer of CYP1As, did not. (nih.gov)
  • CYP3A4 (AAI01632.1, 1 a.a. ~ 503 a.a) full-length human protein. (sigmaaldrich.com)
Mechanism1
  • No single mechanism can account for the loss of protein into the GI tract seen in a wide range of underlying clinical conditions. (medscape.com)
Targets2
  • Learn more about their rise in oncology, inflammatory, and immune disease treatment through trends, protein targets, scientific mechanisms, and more in our latest article . (cas.org)
  • Synapsins are well established targets for multiple protein kinases within the nerve terminal, yet little is known about dephosphorylation processes involved in regulation of synapsin function. (ucl.ac.uk)
Substrates1
  • Several additional diagnostic techniques using radiolabeled substrates were developed, but a major advance was made when Crossley and Elliot demonstrated that measurement of alpha1-antitrypsin (A1-AT) levels in the stool was a reliable and simple test for protein-losing enteropathy. (medscape.com)
Toxic2
  • Cyclosporin G is a new immunosuppressor structurally similar to cyclosporin A. Although this drug is pharmacologically as active as cyclosporin A, it is less toxic, in particular at the kidney level. (nih.gov)
  • cyclosporin A 50 mg/kg i.v. was toxic. (usuhs.edu)
Endoplasmic reticulum1
  • This protein localizes to the endoplasmic reticulum and its expression is induced by glucocorticoids and some pharmacological agents. (sigmaaldrich.com)
Molecular3
  • Molecular glues and targeted protein degraders are changing the landscape of drug discovery. (cas.org)
  • Dr. Ebert started off with discussing some of the natural molecular glues such as Cyclosporin and molecular glues that do not utilize the E3 ligase for protein destruction, such as FK-506. (cas.org)
  • In short, this was an engaging panel that highlights future opportunities with molecular glues, targeted protein degraders, and the treatment of diseases with high unmet needs moving forward. (cas.org)
Concentration1
  • Rats were subjected to experimental TBI and given one of five intravenous doses of cyclosporin A. At 3 h post-injury, brains were processed for brain tissue cyclosporin A concentration. (usuhs.edu)
Drug1
  • Neither drug inhibited transport of a fluorescent cyclosporin A derivative on P-glycoprotein. (aspetjournals.org)
Purification1
  • Tissue culture supernatant is purified by either protein A/G or affinity purification methods. (bdbiosciences.com)
Vitro1
  • In vitro analyses have demonstrated that loss of these proteoglycans not only directly causes protein-losing enteropathy but also potentiates the effects of other reputed factors such as inflammatory cytokines and increased lymphatic pressure. (medscape.com)
Diseases1
  • Protein-losing enteropathy can be either a primary manifestation or a subclinical component of various diseases. (medscape.com)
Processes3
  • 3} MAS is postulated to occur due to a defective function of perforin, a protein involved in the cytolytic processes and control of lymphocyte proliferation. (pediatriconcall.com)
  • While it occurs in multiple conditions through various pathophysiologic processes, the end result is the loss of serum proteins into the GI tract. (medscape.com)
  • For practical purposes, the disease processes that cause protein-losing enteropathy can be grouped into the following 3 major categories: (1) lymphatic obstruction (2) mucosal erosion or ulceration, and (3) epithelial cell dysfunction in the absence of macroscopic compromise. (medscape.com)
Factor2
  • Aberrant DNA methylation of GATA binding protein 3 (GATA3), interleukin-4 (IL-4), and transforming growth factor-β (TGF-β) promoters in. (oncotarget.com)
  • 4} Other agents used for treatment include cyclosporin A {cy A}and anti-Tumor Necrosis Factor {TNF} therapy. (pediatriconcall.com)
Include1
  • Although enteropathy implies an intestinal disease associated with the small bowel, the term protein-losing enteropathy is commonly used to also include loss of protein from the colon, stomach, and, rarely, the esophagus. (medscape.com)
Found1
  • Similar results were also found in cyclosporin A (CsA) treated HUVECs. (bvsalud.org)
Specific1
  • This protein is a specific component of the complex that includes pre-mRNA processing factors PRPF3, PRPF4, and PRPF18, as well as U4/U5/U6 tri-snRNP. (nih.gov)
Families1
  • The three families are structurally unrelated and can be distinguished by being inhibited by cyclosporin A, FK-506 and 5-hydroxy-1,4-naphthoquinone, respectively. (cathdb.info)