A CALCIUM and CALMODULIN-dependent serine/threonine protein phosphatase that is composed of the calcineurin A catalytic subunit and the calcineurin B regulatory subunit. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including HISTONES; MYOSIN LIGHT CHAIN; and the regulatory subunits of CAMP-DEPENDENT PROTEIN KINASES. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes.
A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.
A family of transcription factors characterized by the presence of highly conserved calcineurin- and DNA-binding domains. NFAT proteins are activated in the CYTOPLASM by the calcium-dependent phosphatase CALCINEURIN. They transduce calcium signals to the nucleus where they can interact with TRANSCRIPTION FACTOR AP-1 or NF-KAPPA B and initiate GENETIC TRANSCRIPTION of GENES involved in CELL DIFFERENTIATION and development. NFAT proteins stimulate T-CELL activation through the induction of IMMEDIATE-EARLY GENES such as INTERLEUKIN-2.
A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).
Proteins which bind calmodulin. They are found in many tissues and have a variety of functions including F-actin cross-linking properties, inhibition of cyclic nucleotide phosphodiesterase and calcium and magnesium ATPases.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)
A family of immunophilin proteins that bind to the immunosuppressive drugs TACROLIMUS (also known as FK506) and SIROLIMUS. EC 5.2.1.-
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
A 12-KDa tacrolimus binding protein that is found associated with and may modulate the function of calcium release channels. It is a peptidyl-prolyl cis/trans isomerase which is inhibited by both tacrolimus (commonly called FK506) and SIROLIMUS.
Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.
Enzymes that catalyze either the racemization or epimerization of chiral centers within amino acids or derivatives. EC 5.1.1.
A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.
A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3.
Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.
Members of a family of highly conserved proteins which are all cis-trans peptidyl-prolyl isomerases (PEPTIDYLPROLYL ISOMERASE). They bind the immunosuppressant drugs CYCLOSPORINE; TACROLIMUS and SIROLIMUS. They possess rotamase activity, which is inhibited by the immunosuppressant drugs that bind to them.
The transference of a kidney from one human or animal to another.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
An enzyme that catalyzes the isomerization of proline residues within proteins. EC 5.2.1.8.
The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
An antibiotic substance derived from Penicillium stoloniferum, and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1301)
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.
Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)
A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.
A specific inhibitor of phosphoserine/threonine protein phosphatase 1 and 2a. It is also a potent tumor promoter. (Thromb Res 1992;67(4):345-54 & Cancer Res 1993;53(2):239-41)
A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions.

The role of immunophilins in mutant superoxide dismutase-1linked familial amyotrophic lateral sclerosis. (1/2213)

It has been reported that expression of familial amyotrophic lateral sclerosis (FALS)-associated mutant Cu/Zn superoxide dismutase-1 (SOD) induces apoptosis of neuronal cells in culture associated with an increase in reactive oxygen species. SOD recently has been shown to prevent calcineurin inactivation, initiating the present investigations examining the role of calcineurin in mutant SOD-induced cell death. Wild-type or mutant SOD was expressed in neuronal cells by infection with replication-deficient adenoviruses. PC12 cells overexpressing human wild-type SOD exhibited higher calcineurin activity than cells expressing FALS-related mutant SOD (SODV148G); however, cells expressing SODV148G had calcineurin activity equal to mock-infected cells, suggesting that cell death induced by mutant SOD was not related to a decrease in calcineurin activity. Calcineurin antagonists such as cyclosporin A and FK506, as well as nonimmunosuppressant analogs of cyclosporin A, significantly enhanced SODV148G- and SODA4V-induced cell death. Because both groups of drugs inhibit the rotamase activity of cyclophilins (CyP), but only the immunosuppressant analogs inhibit calcineurin activity, these data suggest that rotamase inhibition underlies the enhanced cell death after SODV148G expression. The importance of rotamase activity in mutant SOD-mediated apoptosis was supported by experiments showing that overexpressed wild-type cyclophilin A (CyPA), but not CyPA with a rotamase active site point mutation, protected cells from death after SODV148G expression. These data suggest that mutant SOD produces a greater need for rotamase and, also, highlights possible new therapeutic strategies in FALS.  (+info)

Differential effects of a calcineurin inhibitor on glutamate-induced phosphorylation of Ca2+/calmodulin-dependent protein kinases in cultured rat hippocampal neurons. (2/2213)

Calcium/calmodulin-dependent protein kinases (CaM kinases) are major multifunctional enzymes that play important roles in calcium-mediated signal transduction. To characterize their regulatory mechanisms in neurons, we compared glutamate-induced phosphorylation of CaM kinase IV and CaM kinase II in cultured rat hippocampal neurons. We observed that dephosphorylation of these kinases followed different time courses, suggesting different regulatory mechanisms for each kinase. Okadaic acid, an inhibitor of protein phosphatase (PP) 1 and PP2A, increased the phosphorylation of both kinases. In contrast, cyclosporin A, an inhibitor of calcineurin, showed different effects: the phosphorylation and activity of CaM kinase IV were significantly increased with this inhibitor, but those of CaM kinase II were not significantly increased. Cyclosporin A treatment of neurons increased phosphorylation of Thr196 of CaM kinase IV, the activated form with CaM kinase kinase, which was recognized with an anti-phospho-Thr196 antibody. Moreover, recombinant CaM kinase IV was dephosphorylated and inactivated with calcineurin as well as with PP1, PP2A, and PP2C in vitro. These results suggest that CaM kinase IV, but not CaM kinase II, is directly regulated with calcineurin.  (+info)

Reduction of calcineurin activity in brain by antisense oligonucleotides leads to persistent phosphorylation of tau protein at Thr181 and Thr231. (3/2213)

Phosphorylation of tau protein promotes stability of the axonal cytoskeleton; aberrant tau phosphorylation is implicated in the biogenesis of paired helical filaments (PHF) seen in Alzheimer's disease. Protein kinases and phosphatases that modulate tau phosphorylation have been identified using in vitro techniques; however, the role of these enzymes in vivo has not been determined. We used intraventricular infusions of antisense oligodeoxynucleotides (ODNs) directed against the major brain isoforms of the Ca2+/calmodulin-dependent phosphatase calcineurin to determine how reduced activity of this enzyme would affect tau dephosphorylation. Five-day infusions of antisense ODNs (5 and 10 nmol/day) in rats decreased immunoreactive levels and activity of calcineurin throughout the brain; sense ODNs, scrambled ODNs, and infusion vehicle alone had no effect. When neocortical slices were prepared from antisense ODN-treated rats and incubated for 1 to 2 h in vitro, tau protein remained phosphorylated as determined by using the phosphorylation-sensitive monoclonal antibodies AT-180 (Thr231) and AT-270 (Thr181). In contrast, AT-180 and AT-270 sites were completely dephosphorylated during incubation of neocortical slices from vehicle-infused controls and sense ODN-treated rats. Neocortical slices from antisense-treated rats were incubated with the phosphatase inhibitors okadaic acid (100 nM; 10 microM) and FK-520 (5 microM); these preparations showed enhanced tau phosphorylation, consistent with a significant loss of calcineurin activity. Thus, we conclude that phosphorylation of at least two sites on tau protein, namely, Thr181 and Thr231, is regulated by calcineurin.  (+info)

Failure of calcineurin inhibitors to prevent pressure-overload left ventricular hypertrophy in rats. (4/2213)

A rapidly emerging body of literature implicates a pivotal role for the Ca2+-calmodulin-dependent phosphatase calcineurin as a cellular target for a variety of Ca2+-dependent signaling pathways culminating in left ventricular hypertrophy (LVH). Most of the recent experimental support for this hypothesis is derived from in vitro studies or in vivo studies in transgenic mice expressing activated calcineurin or mutant sarcomeric proteins. The aim of the present study was to test whether calcineurin inhibitors, cyclosporin A (CsA) and FK 506, prevent pressure-overload LVH using 2 standard rat models: (1) the spontaneously hypertensive rat (SHR) and (2) aortic banding. The major new findings are 2-fold. First, in SHR, LVH (left ventricular weight to body weight ratio) was unaffected by a dose of CsA (5 mg. kg-1. d-1) that was sufficient to raise blood pressure and to inhibit calcineurin-mediated transcriptional activation in skeletal muscle. Second, in rats with aortic banding, LVH was unaffected by FK 506 (0.3 mg. kg-1. d-1) or even higher doses of CsA (10 and 20 mg. kg-1. d-1) that were sufficient to inhibit 90% of total calcineurin phosphatase activity in the hypertrophied myocardium. In the latter experiments, CsA blocked neither the elevated left ventricular end-diastolic pressures, a measure of diastolic function, nor the induction in atrial natriuretic peptide mRNA in the hypertrophic ventricles. Thus, in numerous experiments, systemic administration of potent calcineurin inhibitors did not prevent the development of LVH in 2 classic models of pressure-overload hypertrophy. These results demonstrate that pressure-overload hypertrophy can arise through calcineurin-independent pathways.  (+info)

Pressure overload induces severe hypertrophy in mice treated with cyclosporine, an inhibitor of calcineurin. (5/2213)

Cardiac hypertrophy is the fundamental adaptation of the adult heart to mechanical load. Recent work has shown that inhibition of calcineurin activity with cyclosporine suppresses the development of hypertrophy in calcineurin transgenic mice and in in vitro systems of neonatal rat cardiocytes stimulated with peptide growth factors. To test the hypothesis that the calcineurin signaling pathway is critical for load-induced hypertrophy in vivo, we examined the effects of cyclosporine treatment on left ventricular hypertrophy induced by experimental ascending aortic stenosis for 4 weeks in mice. Left ventricular systolic pressure was elevated to a similar level in aortic stenosis mice that were treated with cyclosporine versus no drug. Left ventricular mass and myocyte size were similar in treated and untreated aortic stenosis animals and significantly greater than control animals, showing that cyclosporine treatment does not suppress hypertrophic growth. Both treated and untreated animals showed increased left ventricular expression of the load-sensitive gene atrial natriuretic factor. Calcineurin activity was measured in the left ventricle and the spleen from control mice and aortic stenosis mice treated with cyclosporine versus no drug. Levels of calcineurin activity were similar in the spleens of control and untreated aortic stenosis mice. However, calcineurin activity was severely depressed in left ventricular tissue of untreated aortic stenosis mice compared with control mice and was further reduced by cyclosporine treatment. Thus, pathological hypertrophy and cardiac-restricted gene expression induced by pressure overload in vivo are not suppressed by treatment with cyclosporine and do not appear to depend on the elevation of left ventricular calcineurin activity.  (+info)

Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD. (6/2213)

The Ca2+-activated protein phosphatase calcineurin induces apoptosis, but the mechanism is unknown. Calcineurin was found to dephosphorylate BAD, a pro-apoptotic member of the Bcl-2 family, thus enhancing BAD heterodimerization with Bcl-xL and promoting apoptosis. The Ca2+-induced dephosphorylation of BAD correlated with its dissociation from 14-3-3 in the cytosol and translocation to mitochondria where Bcl-xL resides. In hippocampal neurons, L-glutamate, an inducer of Ca2+ influx and calcineurin activation, triggered mitochondrial targeting of BAD and apoptosis, which were both suppressible by coexpression of a dominant-inhibitory mutant of calcineurin or pharmacological inhibitors of this phosphatase. Thus, a Ca2+-inducible mechanism for apoptosis induction operates by regulating BAD phosphorylation and localization in cells.  (+info)

Yeast calcineurin regulates nuclear localization of the Crz1p transcription factor through dephosphorylation. (7/2213)

Calcineurin, a Ca2+/calmodulin dependent protein phosphatase, regulates Ca2+-dependent processes in a wide variety of cells. In the yeast, Saccharomyces cerevisiae, calcineurin effects Ca2+-dependent changes in gene expression through regulation of the Crz1p transcription factor. We show here that calcineurin dephosphorylates Crz1p and that this results in translocation of Crz1p to the nucleus. We identify a region of Crz1p that is required for calcineurin-dependent regulation of its phosphorylation, localization, and activity, and show that this region has significant sequence simlarity to a portion of NF-AT, a family of mammalian transcription factors whose localization is also regulated by calcineurin. Thus, the mechanism of Ca2+/calcineurin-dependent signaling shows remarkable conservation between yeast and mammalian cells.  (+info)

A selective role of calcineurin aalpha in synaptic depotentiation in hippocampus. (8/2213)

Pharmacological studies have suggested that long-term potentiation (LTP) and long-term depression (LTD) and depotentiation, three forms of synaptic plasticity in the hippocampus, require the activity of the phosphatase calcineurin. At least two different isoforms of calcineurin are found in the central nervous system. To investigate whether all of these forms of synaptic plasticity require the same isoforms of calcineurin, we have examined LTD, depotentiation, and LTP in mice lacking the predominant calcineurin isoform in the central nervous system, Aalpha-/- mice. Depotentiation was abolished completely whereas neither LTD nor LTP were affected. These studies provide genetic evidence that the Aalpha isoform of calcineurin is important for the reversal of LTP in the hippocampus and indicate that depotentiation and LTD operate through somewhat different molecular mechanisms.  (+info)

Calcineurin is a calcium-calmodulin-activated serine/threonine protein phosphatase that plays a crucial role in signal transduction pathways involved in immune response and neuronal development. It consists of two subunits: the catalytic A subunit (calcineurin A) and the regulatory B subunit (calcineurin B). Calcineurin is responsible for dephosphorylating various substrates, including transcription factors, which leads to changes in their activity and ultimately affects gene expression. In the immune system, calcineurin plays a critical role in T-cell activation by dephosphorylating the nuclear factor of activated T-cells (NFAT), allowing it to translocate into the nucleus and induce the expression of cytokines and other genes involved in the immune response. Inhibitors of calcineurin, such as cyclosporine A and tacrolimus, are commonly used as immunosuppressive drugs to prevent organ rejection after transplantation.

Tacrolimus is an immunosuppressant drug that is primarily used to prevent the rejection of transplanted organs. It works by inhibiting the activity of T-cells, which are a type of white blood cell that plays a central role in the body's immune response. By suppressing the activity of these cells, tacrolimus helps to reduce the risk of an immune response being mounted against the transplanted organ.

Tacrolimus is often used in combination with other immunosuppressive drugs, such as corticosteroids and mycophenolate mofetil, to provide a comprehensive approach to preventing organ rejection. It is available in various forms, including capsules, oral solution, and intravenous injection.

The drug was first approved for use in the United States in 1994 and has since become a widely used immunosuppressant in transplant medicine. Tacrolimus is also being studied as a potential treatment for a variety of other conditions, including autoimmune diseases and cancer.

Nuclear factor of activated T-cells (NFAT) transcription factors are a group of proteins that play a crucial role in the regulation of gene transcription in various cells, including immune cells. They are involved in the activation of genes responsible for immune responses, cell survival, differentiation, and development.

NFAT transcription factors can be divided into five main members: NFATC1 (also known as NFAT2 or NFATp), NFATC2 (or NFAT1), NFATC3 (or NFATc), NFATC4 (or NFAT3), and NFAT5 (or TonEBP). These proteins share a highly conserved DNA-binding domain, known as the Rel homology region, which allows them to bind to specific sequences in the promoter or enhancer regions of target genes.

NFATC transcription factors are primarily located in the cytoplasm in their inactive form, bound to inhibitory proteins. Upon stimulation of the cell, typically through calcium-dependent signaling pathways, NFAT proteins get dephosphorylated by calcineurin phosphatase, leading to their nuclear translocation and activation. Once in the nucleus, NFATC transcription factors can form homodimers or heterodimers with other transcription factors, such as AP-1, to regulate gene expression.

In summary, NFATC transcription factors are a family of proteins involved in the regulation of gene transcription, primarily in immune cells, and play critical roles in various cellular processes, including immune responses, differentiation, and development.

Cyclosporine is a medication that belongs to a class of drugs called immunosuppressants. It is primarily used to prevent the rejection of transplanted organs, such as kidneys, livers, and hearts. Cyclosporine works by suppressing the activity of the immune system, which helps to reduce the risk of the body attacking the transplanted organ.

In addition to its use in organ transplantation, cyclosporine may also be used to treat certain autoimmune diseases, such as rheumatoid arthritis and psoriasis. It does this by suppressing the overactive immune response that contributes to these conditions.

Cyclosporine is available in capsule, oral solution, and injectable forms. Common side effects of the medication include kidney problems, high blood pressure, tremors, headache, and nausea. Long-term use of cyclosporine can also increase the risk of certain types of cancer and infections.

It is important to note that cyclosporine should only be used under the close supervision of a healthcare provider, as it requires regular monitoring of blood levels and kidney function.

Calmodulin-binding proteins are a diverse group of proteins that have the ability to bind to calmodulin, a ubiquitous calcium-binding protein found in eukaryotic cells. Calmodulin plays a critical role in various cellular processes by regulating the activity of its target proteins in a calcium-dependent manner.

Calmodulin-binding proteins contain specific domains or motifs that enable them to interact with calmodulin. These domains can be classified into two main categories: IQ motifs and CaM motifs. The IQ motif is a short amino acid sequence that contains the consensus sequence IQXXXRGXXR, where X represents any amino acid. This motif binds to the C-lobe of calmodulin in a calcium-dependent manner. On the other hand, CaM motifs are longer sequences that can bind to both lobes of calmodulin with high affinity and in a calcium-dependent manner.

Calmodulin-binding proteins play crucial roles in various cellular functions, including signal transduction, gene regulation, cytoskeleton organization, and ion channel regulation. For example, calmodulin-binding proteins such as calcineurin and CaM kinases are involved in the regulation of immune responses, learning, and memory. Similarly, myosin regulatory light chains, which contain IQ motifs, play a critical role in muscle contraction by regulating the interaction between actin and myosin filaments.

In summary, calmodulin-binding proteins are a diverse group of proteins that interact with calmodulin to regulate various cellular processes. They contain specific domains or motifs that enable them to bind to calmodulin in a calcium-dependent manner, thereby modulating the activity of their target proteins.

Immunosuppressive agents are medications that decrease the activity of the immune system. They are often used to prevent the rejection of transplanted organs and to treat autoimmune diseases, where the immune system mistakenly attacks the body's own tissues. These drugs work by interfering with the immune system's normal responses, which helps to reduce inflammation and damage to tissues. However, because they suppress the immune system, people who take immunosuppressive agents are at increased risk for infections and other complications. Examples of immunosuppressive agents include corticosteroids, azathioprine, cyclophosphamide, mycophenolate mofetil, tacrolimus, and sirolimus.

Phosphoprotein phosphatases (PPPs) are a family of enzymes that play a crucial role in the regulation of various cellular processes by removing phosphate groups from serine, threonine, and tyrosine residues on proteins. Phosphorylation is a post-translational modification that regulates protein function, localization, and stability, and dephosphorylation by PPPs is essential for maintaining the balance of this regulation.

The PPP family includes several subfamilies, such as PP1, PP2A, PP2B (also known as calcineurin), PP4, PP5, and PP6. Each subfamily has distinct substrate specificities and regulatory mechanisms. For example, PP1 and PP2A are involved in the regulation of metabolism, signal transduction, and cell cycle progression, while PP2B is involved in immune response and calcium signaling.

Dysregulation of PPPs has been implicated in various diseases, including cancer, neurodegenerative disorders, and cardiovascular disease. Therefore, understanding the function and regulation of PPPs is important for developing therapeutic strategies to target these diseases.

Tacrolimus binding proteins, also known as FK506 binding proteins (FKBPs), are a group of intracellular proteins that bind to the immunosuppressive drug tacrolimus (also known as FK506) and play a crucial role in its mechanism of action. Tacrolimus is primarily used in organ transplantation to prevent rejection of the transplanted organ.

FKBPs are a family of peptidyl-prolyl cis-trans isomerases (PPIases) that catalyze the conversion of proline residues from their cis to trans conformations in proteins, thereby regulating protein folding and function. FKBP12, a member of this family, has a high affinity for tacrolimus and forms a complex with it upon entry into the cell.

The formation of the tacrolimus-FKBP12 complex inhibits calcineurin, a serine/threonine phosphatase that plays a critical role in T-cell activation. Calcineurin inhibition prevents the dephosphorylation and nuclear translocation of the transcription factor NFAT (nuclear factor of activated T-cells), thereby blocking the expression of genes involved in T-cell activation, proliferation, and cytokine production.

In summary, tacrolimus binding proteins are intracellular proteins that bind to tacrolimus and inhibit calcineurin, leading to the suppression of T-cell activation and immune response, which is essential in organ transplantation and other immunological disorders.

Calcium is an essential mineral that is vital for various physiological processes in the human body. The medical definition of calcium is as follows:

Calcium (Ca2+) is a crucial cation and the most abundant mineral in the human body, with approximately 99% of it found in bones and teeth. It plays a vital role in maintaining structural integrity, nerve impulse transmission, muscle contraction, hormonal secretion, blood coagulation, and enzyme activation.

Calcium homeostasis is tightly regulated through the interplay of several hormones, including parathyroid hormone (PTH), calcitonin, and vitamin D. Dietary calcium intake, absorption, and excretion are also critical factors in maintaining optimal calcium levels in the body.

Hypocalcemia refers to low serum calcium levels, while hypercalcemia indicates high serum calcium levels. Both conditions can have detrimental effects on various organ systems and require medical intervention to correct.

Signal transduction is the process by which a cell converts an extracellular signal, such as a hormone or neurotransmitter, into an intracellular response. This involves a series of molecular events that transmit the signal from the cell surface to the interior of the cell, ultimately resulting in changes in gene expression, protein activity, or metabolism.

The process typically begins with the binding of the extracellular signal to a receptor located on the cell membrane. This binding event activates the receptor, which then triggers a cascade of intracellular signaling molecules, such as second messengers, protein kinases, and ion channels. These molecules amplify and propagate the signal, ultimately leading to the activation or inhibition of specific cellular responses.

Signal transduction pathways are highly regulated and can be modulated by various factors, including other signaling molecules, post-translational modifications, and feedback mechanisms. Dysregulation of these pathways has been implicated in a variety of diseases, including cancer, diabetes, and neurological disorders.

Calmodulin is a small, ubiquitous calcium-binding protein that plays a critical role in various intracellular signaling pathways. It functions as a calcium sensor, binding to and regulating the activity of numerous target proteins upon calcium ion (Ca^2+^) binding. Calmodulin is expressed in all eukaryotic cells and participates in many cellular processes, including muscle contraction, neurotransmitter release, gene expression, metabolism, and cell cycle progression.

The protein contains four EF-hand motifs that can bind Ca^2+^ ions. Upon calcium binding, conformational changes occur in the calmodulin structure, exposing hydrophobic surfaces that facilitate its interaction with target proteins. Calmodulin's targets include enzymes (such as protein kinases and phosphatases), ion channels, transporters, and cytoskeletal components. By modulating the activity of these proteins, calmodulin helps regulate essential cellular functions in response to changes in intracellular Ca^2+^ concentrations.

Calmodulin's molecular weight is approximately 17 kDa, and it consists of a single polypeptide chain with 148-150 amino acid residues. The protein can be found in both the cytoplasm and the nucleus of cells. In addition to its role as a calcium sensor, calmodulin has been implicated in various pathological conditions, including cancer, neurodegenerative diseases, and cardiovascular disorders.

Tacrolimus Binding Protein 1A, also known as FKBP12 or FK506 binding protein 12, is a intracellular protein that binds to the immunosuppressive drug tacrolimus (FK506) and forms a complex. This complex inhibits the calcium-dependent serine/threonine phosphatase calcineurin, which plays a crucial role in T-cell activation. By inhibiting calcineurin, tacrolimus suppresses the immune response, particularly the activation of T-lymphocytes, and is used to prevent rejection in organ transplantation. FKBP12 is a member of the immunophilin family and has peptidyl-prolyl cis-trans isomerase activity.

Cardiomegaly is a medical term that refers to an enlarged heart. It can be caused by various conditions such as high blood pressure, heart valve problems, cardiomyopathy, or fluid accumulation around the heart (pericardial effusion). Cardiomegaly can be detected through imaging tests like chest X-rays or echocardiograms. Depending on the underlying cause, treatment options may include medications, lifestyle changes, or in some cases, surgery. It is important to consult with a healthcare professional for proper diagnosis and treatment.

Amino acid isomerases are a class of enzymes that catalyze the conversion of one amino acid stereoisomer to another. These enzymes play a crucial role in the metabolism and biosynthesis of amino acids, which are the building blocks of proteins.

Amino acids can exist in two forms, called L- and D-stereoisomers, based on the spatial arrangement of their constituent atoms around a central carbon atom. While most naturally occurring amino acids are of the L-configuration, some D-amino acids are also found in certain proteins and peptides, particularly in bacteria and lower organisms.

Amino acid isomerases can convert one stereoisomer to another by breaking and reforming chemical bonds in a process that requires energy. This conversion can be important for the proper functioning of various biological processes, such as protein synthesis, neurotransmitter metabolism, and immune response.

Examples of amino acid isomerases include proline racemase, which catalyzes the interconversion of L-proline and D-proline, and serine hydroxymethyltransferase, which converts L-serine to D-serine. These enzymes are essential for maintaining the balance of amino acids in living organisms and have potential therapeutic applications in various diseases, including neurodegenerative disorders and cancer.

Sirolimus is a medication that belongs to a class of drugs called immunosuppressants. It is also known as rapamycin. Sirolimus works by inhibiting the mammalian target of rapamycin (mTOR), which is a protein that plays a key role in cell growth and division.

Sirolimus is primarily used to prevent rejection of transplanted organs, such as kidneys, livers, and hearts. It works by suppressing the activity of the immune system, which can help to reduce the risk of the body rejecting the transplanted organ. Sirolimus is often used in combination with other immunosuppressive drugs, such as corticosteroids and calcineurin inhibitors.

Sirolimus is also being studied for its potential therapeutic benefits in a variety of other conditions, including cancer, tuberous sclerosis complex, and lymphangioleiomyomatosis. However, more research is needed to fully understand the safety and efficacy of sirolimus in these contexts.

It's important to note that sirolimus can have significant side effects, including increased risk of infections, mouth sores, high blood pressure, and kidney damage. Therefore, it should only be used under the close supervision of a healthcare provider.

Phosphoric monoester hydrolases are a class of enzymes that catalyze the hydrolysis of phosphoric monoesters into alcohol and phosphate. This class of enzymes includes several specific enzymes, such as phosphatases and nucleotidases, which play important roles in various biological processes, including metabolism, signal transduction, and regulation of cellular processes.

Phosphoric monoester hydrolases are classified under the EC number 3.1.3 by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (IUBMB). The enzymes in this class share a common mechanism of action, which involves the nucleophilic attack on the phosphorus atom of the substrate by a serine or cysteine residue in the active site of the enzyme. This results in the formation of a covalent intermediate, which is then hydrolyzed to release the products.

Phosphoric monoester hydrolases are important therapeutic targets for the development of drugs that can modulate their activity. For example, inhibitors of phosphoric monoester hydrolases have been developed as potential treatments for various diseases, including cancer, neurodegenerative disorders, and infectious diseases.

Calcium signaling is the process by which cells regulate various functions through changes in intracellular calcium ion concentrations. Calcium ions (Ca^2+^) are crucial second messengers that play a critical role in many cellular processes, including muscle contraction, neurotransmitter release, gene expression, and programmed cell death (apoptosis).

Intracellular calcium levels are tightly regulated by a complex network of channels, pumps, and exchangers located on the plasma membrane and intracellular organelles such as the endoplasmic reticulum (ER) and mitochondria. These proteins control the influx, efflux, and storage of calcium ions within the cell.

Calcium signaling is initiated when an external signal, such as a hormone or neurotransmitter, binds to a specific receptor on the plasma membrane. This interaction triggers the opening of ion channels, allowing extracellular Ca^2+^ to flow into the cytoplasm. In some cases, this influx of calcium ions is sufficient to activate downstream targets directly. However, in most instances, the increase in intracellular Ca^2+^ serves as a trigger for the release of additional calcium from internal stores, such as the ER.

The release of calcium from the ER is mediated by ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs), which are activated by specific second messengers generated in response to the initial external signal. The activation of these channels leads to a rapid increase in cytoplasmic Ca^2+^, creating a transient intracellular calcium signal known as a "calcium spark" or "calcium puff."

These localized increases in calcium concentration can then propagate throughout the cell as waves of elevated calcium, allowing for the spatial and temporal coordination of various cellular responses. The duration and amplitude of these calcium signals are finely tuned by the interplay between calcium-binding proteins, pumps, and exchangers, ensuring that appropriate responses are elicited in a controlled manner.

Dysregulation of intracellular calcium signaling has been implicated in numerous pathological conditions, including neurodegenerative diseases, cardiovascular disorders, and cancer. Therefore, understanding the molecular mechanisms governing calcium homeostasis and signaling is crucial for the development of novel therapeutic strategies targeting these diseases.

Immunophilins are a group of intracellular proteins that have peptidyl-prolyl isomerase (PPIase) activity, which enables them to catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. They play crucial roles in protein folding, trafficking, and assembly, as well as in immunoregulation and signal transduction processes.

Two major classes of immunophilins are FK506-binding proteins (FKBPs) and cyclophilins. These proteins can bind to immunosuppressive drugs like FK506 (tacrolimus) and cyclosporin A, respectively, forming complexes that inhibit the activity of calcineurin, a phosphatase involved in T-cell activation. This interaction leads to an inhibition of immune responses and is exploited in transplantation medicine to prevent graft rejection.

Immunophilins also participate in various cellular processes, such as protein trafficking, neuroprotection, and regulation of gene expression, by interacting with other proteins or acting as chaperones during protein folding. Dysregulation of immunophilin function has been implicated in several diseases, including cancer, neurological disorders, and viral infections.

Kidney transplantation is a surgical procedure where a healthy kidney from a deceased or living donor is implanted into a patient with end-stage renal disease (ESRD) or permanent kidney failure. The new kidney takes over the functions of filtering waste and excess fluids from the blood, producing urine, and maintaining the body's electrolyte balance.

The transplanted kidney is typically placed in the lower abdomen, with its blood vessels connected to the recipient's iliac artery and vein. The ureter of the new kidney is then attached to the recipient's bladder to ensure proper urine flow. Following the surgery, the patient will require lifelong immunosuppressive therapy to prevent rejection of the transplanted organ by their immune system.

Transcription factors are proteins that play a crucial role in regulating gene expression by controlling the transcription of DNA to messenger RNA (mRNA). They function by binding to specific DNA sequences, known as response elements, located in the promoter region or enhancer regions of target genes. This binding can either activate or repress the initiation of transcription, depending on the properties and interactions of the particular transcription factor. Transcription factors often act as part of a complex network of regulatory proteins that determine the precise spatiotemporal patterns of gene expression during development, differentiation, and homeostasis in an organism.

Phosphorylation is the process of adding a phosphate group (a molecule consisting of one phosphorus atom and four oxygen atoms) to a protein or other organic molecule, which is usually done by enzymes called kinases. This post-translational modification can change the function, localization, or activity of the target molecule, playing a crucial role in various cellular processes such as signal transduction, metabolism, and regulation of gene expression. Phosphorylation is reversible, and the removal of the phosphate group is facilitated by enzymes called phosphatases.

"Cells, cultured" is a medical term that refers to cells that have been removed from an organism and grown in controlled laboratory conditions outside of the body. This process is called cell culture and it allows scientists to study cells in a more controlled and accessible environment than they would have inside the body. Cultured cells can be derived from a variety of sources, including tissues, organs, or fluids from humans, animals, or cell lines that have been previously established in the laboratory.

Cell culture involves several steps, including isolation of the cells from the tissue, purification and characterization of the cells, and maintenance of the cells in appropriate growth conditions. The cells are typically grown in specialized media that contain nutrients, growth factors, and other components necessary for their survival and proliferation. Cultured cells can be used for a variety of purposes, including basic research, drug development and testing, and production of biological products such as vaccines and gene therapies.

It is important to note that cultured cells may behave differently than they do in the body, and results obtained from cell culture studies may not always translate directly to human physiology or disease. Therefore, it is essential to validate findings from cell culture experiments using additional models and ultimately in clinical trials involving human subjects.

Peptidylprolyl Isomerase (PPIase) is an enzyme that catalyzes the cis-trans isomerization of peptidyl-prolyl bonds in proteins. This isomerization process, which involves the rotation around a proline bond, is a rate-limiting step in protein folding and can be a significant factor in the development of various diseases, including neurodegenerative disorders and cancer.

PPIases are classified into three families: cyclophilins, FK506-binding proteins (FKBPs), and parvulins. These enzymes play important roles in protein folding, trafficking, and degradation, as well as in signal transduction pathways and the regulation of gene expression.

Inhibitors of PPIases have been developed as potential therapeutic agents for various diseases, including transplant rejection, autoimmune disorders, and cancer. For example, cyclosporine A and FK506 are immunosuppressive drugs that inhibit cyclophilins and FKBPs, respectively, and are used to prevent transplant rejection.

Muscle proteins are a type of protein that are found in muscle tissue and are responsible for providing structure, strength, and functionality to muscles. The two major types of muscle proteins are:

1. Contractile proteins: These include actin and myosin, which are responsible for the contraction and relaxation of muscles. They work together to cause muscle movement by sliding along each other and shortening the muscle fibers.
2. Structural proteins: These include titin, nebulin, and desmin, which provide structural support and stability to muscle fibers. Titin is the largest protein in the human body and acts as a molecular spring that helps maintain the integrity of the sarcomere (the basic unit of muscle contraction). Nebulin helps regulate the length of the sarcomere, while desmin forms a network of filaments that connects adjacent muscle fibers together.

Overall, muscle proteins play a critical role in maintaining muscle health and function, and their dysregulation can lead to various muscle-related disorders such as muscular dystrophy, myopathies, and sarcopenia.

Enzyme inhibitors are substances that bind to an enzyme and decrease its activity, preventing it from catalyzing a chemical reaction in the body. They can work by several mechanisms, including blocking the active site where the substrate binds, or binding to another site on the enzyme to change its shape and prevent substrate binding. Enzyme inhibitors are often used as drugs to treat various medical conditions, such as high blood pressure, abnormal heart rhythms, and bacterial infections. They can also be found naturally in some foods and plants, and can be used in research to understand enzyme function and regulation.

Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.

DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.

The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.

DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.

An amino acid sequence is the specific order of amino acids in a protein or peptide molecule, formed by the linking of the amino group (-NH2) of one amino acid to the carboxyl group (-COOH) of another amino acid through a peptide bond. The sequence is determined by the genetic code and is unique to each type of protein or peptide. It plays a crucial role in determining the three-dimensional structure and function of proteins.

Mycophenolic Acid (MPA) is an immunosuppressive drug that is primarily used to prevent rejection in organ transplantation. It works by inhibiting the enzyme inosine monophosphate dehydrogenase, which is a key enzyme for the de novo synthesis of guanosine nucleotides, an essential component for the proliferation of T and B lymphocytes. By doing this, MPA reduces the activity of the immune system, thereby preventing it from attacking the transplanted organ.

Mycophenolic Acid is available in two forms: as the sodium salt (Mycophenolate Sodium) and as the morpholinoethyl ester (Mycophenolate Mofetil), which is rapidly hydrolyzed to Mycophenolic Acid after oral administration. Common side effects of MPA include gastrointestinal symptoms such as diarrhea, nausea, and vomiting, as well as an increased risk of infections due to its immunosuppressive effects.

Nuclear proteins are a category of proteins that are primarily found in the nucleus of a eukaryotic cell. They play crucial roles in various nuclear functions, such as DNA replication, transcription, repair, and RNA processing. This group includes structural proteins like lamins, which form the nuclear lamina, and regulatory proteins, such as histones and transcription factors, that are involved in gene expression. Nuclear localization signals (NLS) often help target these proteins to the nucleus by interacting with importin proteins during active transport across the nuclear membrane.

Graft rejection is an immune response that occurs when transplanted tissue or organ (the graft) is recognized as foreign by the recipient's immune system, leading to the activation of immune cells to attack and destroy the graft. This results in the failure of the transplant and the need for additional medical intervention or another transplant. There are three types of graft rejection: hyperacute, acute, and chronic. Hyperacute rejection occurs immediately or soon after transplantation due to pre-existing antibodies against the graft. Acute rejection typically occurs within weeks to months post-transplant and is characterized by the infiltration of T-cells into the graft. Chronic rejection, which can occur months to years after transplantation, is a slow and progressive process characterized by fibrosis and tissue damage due to ongoing immune responses against the graft.

An encyclopedia is a comprehensive reference work containing articles on various topics, usually arranged in alphabetical order. In the context of medicine, a medical encyclopedia is a collection of articles that provide information about a wide range of medical topics, including diseases and conditions, treatments, tests, procedures, and anatomy and physiology. Medical encyclopedias may be published in print or electronic formats and are often used as a starting point for researching medical topics. They can provide reliable and accurate information on medical subjects, making them useful resources for healthcare professionals, students, and patients alike. Some well-known examples of medical encyclopedias include the Merck Manual and the Stedman's Medical Dictionary.

Protein Phosphatase 2 (PP2A) is a type of serine/threonine protein phosphatase that plays a crucial role in the regulation of various cellular processes, including signal transduction, cell cycle progression, and metabolism. PP2A is a heterotrimeric enzyme composed of a catalytic subunit (C), a regulatory subunit A (A), and a variable regulatory subunit B (B). The different combinations of the B subunits confer specificity to PP2A, allowing it to regulate a diverse array of cellular targets.

PP2A is responsible for dephosphorylating many proteins that have been previously phosphorylated by protein kinases. This function is essential for maintaining the balance of phosphorylation and dephosphorylation in cells, which is necessary for proper protein function and cell signaling. Dysregulation of PP2A has been implicated in various diseases, including cancer, neurodegenerative disorders, and cardiovascular disease.

Okadaic acid is a type of toxin that is produced by certain species of marine algae, including Dinophysis and Prorocentrum. It is a potent inhibitor of protein phosphatases 1 and 2A, which are important enzymes that help regulate cellular processes in the body.

Okadaic acid can accumulate in shellfish that feed on these algae, and consumption of contaminated seafood can lead to a serious illness known as diarrhetic shellfish poisoning (DSP). Symptoms of DSP include nausea, vomiting, diarrhea, and abdominal cramps. In severe cases, it can also cause neurological symptoms such as dizziness, disorientation, and tingling or numbness in the lips, tongue, and fingers.

It is important to note that okadaic acid is not only a marine toxin but also used in scientific research as a tool to study the role of protein phosphatases in cellular processes. However, exposure to this compound should be avoided due to its toxic effects.

Protein Phosphatase 1 (PP1) is a type of serine/threonine protein phosphatase that plays a crucial role in the regulation of various cellular processes, including metabolism, signal transduction, and cell cycle progression. PP1 functions by removing phosphate groups from specific serine and threonine residues on target proteins, thereby reversing the effects of protein kinases and controlling protein activity, localization, and stability.

PP1 is a highly conserved enzyme found in eukaryotic cells and is composed of a catalytic subunit associated with one or more regulatory subunits that determine its substrate specificity, subcellular localization, and regulation. The human genome encodes several isoforms of the PP1 catalytic subunit, including PP1α, PP1β/δ, and PP1γ, which share a high degree of sequence similarity and functional redundancy.

PP1 has been implicated in various physiological processes, such as muscle contraction, glycogen metabolism, DNA replication, transcription, and RNA processing. Dysregulation of PP1 activity has been associated with several pathological conditions, including neurodegenerative diseases, cancer, and diabetes. Therefore, understanding the molecular mechanisms that regulate PP1 function is essential for developing novel therapeutic strategies to treat these disorders.

... is a heterodimer of a 61-kD calmodulin-binding catalytic subunit, calcineurin A and a 19-kD Ca2+-binding regulatory ... Calcineurin is the target of a class of drugs called calcineurin inhibitors, which include ciclosporin, voclosporin, ... Calcineurin/NFAT signaling is required for perinatal lung maturation and function. Calcineurin inhibitors such as tacrolimus ... Wang MG, Yi H, Guerini D, Klee CB, McBride OW (1996). "Calcineurin A alpha (PPP3CA), calcineurin A beta (PPP3CB) and ...
The calcineurin-like phosphoesterases are a family of enzymes related to calcineurin. It includes a diverse range of ...
It has protein sequence similarity to calcineurin B and it is also known to be an endogenous inhibitor of calcineurin activity ... Lin X, Sikkink RA, Rusnak F, Barber DL (Dec 1999). "Inhibition of calcineurin phosphatase activity by a calcineurin B ... Calcineurin B homologous protein 1 is a protein encoded in humans by the CHP1 gene (formerly CHP). The protein encoded by this ... Calcineurin B homologous protein 1 has been shown to interact with sodium-hydrogen antiporter 1, sodium-hydrogen antiporter 3, ...
Calcineurin inhibitors and azathioprine have been linked with post-transplant malignancies and skin cancers in organ transplant ... It is a macrolide lactone and acts by inhibiting calcineurin. The drug is used primarily in liver and kidney transplantations, ... It binds to the immunophilin FKBP1A, followed by the binding of the complex to calcineurin and the inhibition of its ... It binds to FKBP1A like tacrolimus, however the complex does not inhibit calcineurin but another protein, mTOR. Therefore, ...
"Calcineurin Inhibitor Nephrotoxicity." Clinical Journal of The American Society of Nephrology, vol. 4, no. 2, 2009, pp. 481-508 ...
Naesens M, Kuypers DR, Sarwal M (2009). "Calcineurin inhibitor nephrotoxicity". Clin. J. Am. Soc. Nephrol. 4 (2): 481-509. doi: ...
... which acts via calmodulin to activate calcineurin. Calcineurin then dephosphorylates the transcription factor nuclear factor of ... Tacrolimus inhibits calcineurin, which is involved in the production of interleukin-2, a molecule that promotes the development ... ISBN 978-0-07-144040-0. Liu J, Farmer JD, Lane WS, Friedman J, Weissman I, Schreiber SL (August 1991). "Calcineurin is a common ... Tacrolimus is a macrolide calcineurin inhibitor. In T-cells, activation of the T-cell receptor normally increases intracellular ...
... 's main effect is to lower the activity of T-cells; it does so by inhibiting calcineurin in the calcineurin- ... which acts via calmodulin to activate calcineurin. Calcineurin then dephosphorylates the transcription factor NF-AT (nuclear ... It does this by forming a complex with cyclophilin to block the phosphatase activity of calcineurin, which in turn decreases ... Cyclosporin A also inhibits the phosphatase calcineurin pathway (14). Inhibition of this pathway has been shown to decrease ...
In molecular biology, the calcipressin family of proteins negatively regulate calcineurin by direct binding. They are essential ... Calcipressin 1 is a phosphoprotein that increases its capacity to inhibit calcineurin when phosphorylated at the conserved ... Calcipressin 1 is also known as modulatory calcineurin-interacting protein 1 (MCIP1), Adapt78 and Down syndrome critical region ... Parry RV, June CH (September 2003). "Calcium-independent calcineurin regulation". Nat. Immunol. 4 (9): 821-3. doi:10.1038/ ...
... inducing a conformational change of the protein such that it can then bind and activate calcineurin. Calcineurin, in turn, ... When dephosphorylated by Calcineurin translocation of NFAT into the nucleus is possible. Additionally, there is evidence that ...
Calcineurin-binding protein cabin-1 is a protein that in humans is encoded by the CABIN1 gene. Calcineurin plays an important ... "Entrez Gene: CABIN1 calcineurin binding protein 1". Lai MM, Luo HR, Burnett PE, Hong JJ, Snyder SH (Nov 2000). "The calcineurin ... The protein encoded by this gene binds specifically to the activated form of calcineurin and inhibits calcineurin-mediated ... Sun L, Youn HD, Loh C, Stolow M, He W, Liu JO (Jun 1998). "Cabin 1, a negative regulator for calcineurin signaling in T ...
These complexes inhibit calcineurin, block dephosphorylation of the transcription factor NFAT of activated T-cells and its ... Liu J, Farmer JD, Lane WS, Friedman J, Weissman I, Schreiber SL (August 1991). "Calcineurin is a common target of cyclophilin- ... Cyclosporine and tacrolimus are calcineurin inhibitors. The substances are structurally different but have the same mechanism ...
Calcineurin activates TAK1 and NLK kinase, which can interfere with TCF/β-Catenin signaling in the canonical Wnt pathway. ... Increased calcium also activates calcineurin and CaMKII. CaMKII induces activation of the transcription factor NFAT, which ...
He investigated the protein-protein interactions between calcineurin and NFAT. Subsequently, he identified ORAI1 as the pore ... Li, Huiming; Rao, Anjana; Hogan, Patrick G. (2011). "Interaction of calcineurin with substrates and targeting proteins". Trends ... Hogan, Patrick G.; Chen, Lin; Nardone, Julie; Rao, Anjana (2003-09-15). "Transcriptional regulation by calcium, calcineurin, ... which is dephosphorylated by the calcium-regulated phosphatase calcineurin, and solved its structure in collaboration with the ...
Calcineurin subunit B type 2 is a protein that in humans is encoded by the PPP3R2 gene. Among its related pathways are MAPK ... 2007). "The calcineurin activity profiles of cyclosporin and tacrolimus are different in stable renal transplant patients". ... 2007). "Calcineurin potentiates the activation of procaspase-3 by accelerating its proteolytic maturation". J. Biol. Chem. 282 ... Jang H, Cho EJ, Youn HD (2007). "A new calcineurin inhibition domain in Cabin1". Biochem. Biophys. Res. Commun. 359 (1): 129-35 ...
When intracellular calcium reaches a threshold, it will activate the calcineurin /NFAT pathway. DAG activates the calcineurin/ ... The mechanism of how TRPC channels promote cardiac hypertrophy is through activation of the calcineurin pathway and the ... canonical transient receptor potential channels promote cardiomyocyte hypertrophy through activation of calcineurin signaling ...
PGC-1α leads to calcineurin activation. Akt and calcineurin are both activators of NF-kappa-B (p65). Through their activation, ...
They also showed that NFAT was regulated by calcium and the calcium-dependent phosphatase calcineurin, which removes phosphate ... Hogan, P. G.; Chen, L.; Nardone, J.; Rao, A. (2003-09-15). "Transcriptional regulation by calcium, calcineurin, and NFAT". ...
... a novel T-cell-specific immunophilin capable of calcineurin inhibition". Molecular and Cellular Biology. 15 (8): 4395-402. doi: ... It is thought to mediate calcineurin inhibition. It also interacts functionally with mature corticoid receptor hetero-complexes ... and FK506-binding protein that can mediate calcineurin inhibition". Biochemical and Biophysical Research Communications. 232 (2 ...
Graef IA, Chen F, Chen L, Kuo A, Crabtree GR (Jun 2001). "Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the ... Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, Grant SR, Olson EN (Apr 1998). "A calcineurin-dependent ... "Entrez Gene: NFATC4 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4". Yang T, Davis RJ, Chow CW (Oct ... Crabtree GR (Mar 1999). "Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT". Cell. 96 (5): ...
Graef IA, Chen F, Chen L, Kuo A, Crabtree GR (June 2001). "Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the ... Esau C, Boes M, Youn HD, Tatterson L, Liu JO, Chen J (November 2001). "Deletion of calcineurin and myocyte enhancer factor 2 ( ... Mukerjee N, McGinnis KM, Gnegy ME, Wang KK (August 2001). "Caspase-mediated calcineurin activation contributes to IL-2 release ... Crabtree GR (March 1999). "Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT". Cell. 96 (5 ...
The orthogonal CID pair was used to inhibit calcineurin-mediated dephosphorylation of nuclear factor of activated T cells in a ... Belshaw, Peter J.; Schreiber, Stuart L. (February 1997). "Cell-Specific Calcineurin Inhibition by a Modified Cyclosporin". ...
The protein encoded by this gene interacts with calcineurin A and inhibits calcineurin-dependent signaling pathways of genetic ... "RCAN1 regulator of calcineurin 1 [ Homo sapiens (human) ]". Retrieved 2022-12-28. Arron JR, Winslow MM, Polleri A, Chang CP, Wu ... DSCR1 in human is located at the centromeric border of the DSCR and encodes an inhibitor of calcineurin/ NFAT (nuclear factor ... Ermak G, Hench KJ, Chang KT, Sachdev S, Davies KJ (May 2009). "Regulator of calcineurin (RCAN1-1L) is deficient in Huntington ...
21, 4066-4073, "Calcineurin Links Ca++ Dysregulation with Brain Aging"( Chen L, Willis SN, Wei A, Smith BJ, Fletcher JI, Hinds ... BAD phosphorylation is thus anti-apoptotic, and BAD dephosphorylation (e.g., by Ca2+-stimulated Calcineurin) is pro-apoptotic. ... "Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD". Science. 284 (5412): 339-43. Bibcode:1999Sci...284..339W ...
Paterson JM, Smith SM, Harmar AJ, Antoni FA (1995). "Control of a novel adenylyl cyclase by calcineurin". Biochem. Biophys. Res ...
This phosphorylation can be reversed by the phosphatase, calcineurin. The phosphorylation of the isozymes is accompanied by a ...
It has been shown in vitro that pimecrolimus binds to FKBP1A and also inhibits calcineurin.[citation needed] Thus pimecrolimus ... Spergel JM, Leung DY (2006). "Safety of topical calcineurin inhibitors in atopic dermatitis: evaluation of the evidence". Curr ... Pimecrolimus is an immunomodulating agent[clarification needed] of the calcineurin inhibitor class used in the treatment of ... Tacrolimus and pimecrolimus are both calcineurin inhibitors and function as immunosuppressants. If topical corticosteroids and ...
March 2015). "Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB". Nature Cell Biology. 17 (3): 288- ...
1998). "A calcineurin-dependent transcriptional pathway for cardiac hypertrophy". Cell. 93 (2): 215-28. doi:10.1016/S0092-8674( ...
Frey N, Richardson JA, Olson EN (2001). "Calsarcins, a novel family of sarcomeric calcineurin-binding proteins". Proc. Natl. ...
Calcineurin is a heterodimer of a 61-kD calmodulin-binding catalytic subunit, calcineurin A and a 19-kD Ca2+-binding regulatory ... Calcineurin is the target of a class of drugs called calcineurin inhibitors, which include ciclosporin, voclosporin, ... Calcineurin/NFAT signaling is required for perinatal lung maturation and function. Calcineurin inhibitors such as tacrolimus ... Wang MG, Yi H, Guerini D, Klee CB, McBride OW (1996). "Calcineurin A alpha (PPP3CA), calcineurin A beta (PPP3CB) and ...
By inhibiting the enzyme calcineurin in immune cells, they interfere with the production of a number of inflammatory substances ... Topical calcineurin inhibitors are non-steroidal immunomodulators. By inhibiting the enzyme calcineurin in immune cells, they ... Pimecrolimus, a newer calcineurin inhibitor, was developed specifically to treat inflammatory skin conditions. Pimecrolimus ... Topical calcineurin inhibitors are non-steroidal immunomodulators. ...
... are a second line treatment of eczema. Find out how Tacrolimus ointment and Pimecrolimus cream can help ... Return from Calcineurin Inhibitors to Eczema Treatments Return from Calcineurin Inhibitors to What is Eczema ... Calcineurin inhibitors havent been used for long periods of times. So there are no studies on the long term effects of using ... Calcineurin Inhibitors.. A Second Line Treatment. For Moderate to Severe Eczema. Tacrolimus ointment and Pimecrolimus cream are ...
Topical calcineurin inhibitors (TCIs) for atopic dermatitis, a.k.a. eczema, did not seem to up the long-term risk for ... Calcineurin Blockers for Eczema: No Cancer Signal in Big Study. - Clinicians can use this evidence to counsel and reassure ... Exposure to topical calcineurin inhibitors also showed no elevated risk for BCC when compared to those not exposed to either ... And in a secondary analysis, the dosage, frequency of use, and the duration of topical calcineurin inhibitor use had no ...
We harnessed unbiased systematic approaches for SLiM discovery to elucidate the regulatory network of calcineurin (CN)/P … ... Systematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling Mol Cell. 2020 Jul 16;79(2):342-358.e12. ... Keywords: NPC; Notch1; ProP-PD; SLiM; Short Linear Motif; calcineurin; calcium signaling; centrosome; in silico motif discovery ... We harnessed unbiased systematic approaches for SLiM discovery to elucidate the regulatory network of calcineurin (CN)/PP2B, ...
The complex Structure of Calmodulin Bound to a Calcineurin Peptide ... The complex structure of calmodulin bound to a calcineurin peptide.. Ye, Q., Wang, H., Zheng, J., Wei, Q., Jia, Z.. (2008) ... The activity of the protein phosphatase calcineurin (CN) is regulated by an autoinhibition mechanism wherein several domains ... The complex Structure of Calmodulin Bound to a Calcineurin Peptide. *PDB DOI: https://doi.org/10.2210/pdb2R28/pdb ...
Calcineurin/PP2B inhibitor (IC50 = 49 nM). Forms a FK-506 binding protein 12 (FKBP12) - Ascomycin -Calcineurin complex. ... Calcineurin/PP2B inhibitor (IC50 = 49 nM). Forms a FK-506 binding protein 12 (FKBP12) - Ascomycin -Calcineurin complex. ... Calcineurin Phosphatase Activity Assay Kit (Colorimetric) (ab139461) *Cellular Calcineurin Phosphatase Activity Assay Kit ( ...
Calcineurin Inhibitors. Class Summary. Topical immunosuppressive agents, such as tacrolimus, have been successfully used to ... Cyclosporine is a calcineurin inhibitor. It is a potent immunosuppressant and is nonmyelotoxic but markedly nephrotoxic. It is ... Pimecrolimus is a calcineurin inhibitor that has an anti-inflammatory effect through decreasing cytokine production. It leads ...
2007). Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis. ... Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis ... Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis. ... We did not find an increased risk of lymphoma in patients treated with topical calcineurin inhibitors. It is difficult to ...
However, calcineurin inhibitor nephrotoxicity (CNIT) has been associated with the development of chronic renal allograft ... Calcineurin inhibitors are highly efficacious immunosuppressive agents used in pediatric kidney transplantation. ... Farouk, S.S.; Rein, J.L. The Many Faces of Calcineurin Inhibitor Toxicity-What the FK? Adv. Chronic Kidney Dis. 2020, 27, 56-66 ... Naesens, M.; Kuypers, D.R.J.; Sarwal, M. Calcineurin Inhibitor Nephrotoxicity. Clin. J. Am. Soc. Nephrol. 2009, 4, 481-508. [ ...
CALCINEURIN INHIBITORS drug classes, patent expirations, and list of drugs by class ... Drugs in MeSH Category Calcineurin Inhibitors. ⮩ Send this page by email. ✉ Email this page to a colleague ...
Calcineurin A antibody - 387 003. Calcineurin is a calcium/calmodulin dependent Ser/Thr protein phosphatase ... Ca2+-binding subunit called calcineurin B. Calcineurin is involved in many cellular processes and Ca2+-dependent signal ... Calcineurin (PP2B) is a calcium/calmodulin dependent Ser/Thr protein phosphatase that is expressed at high levels in the CNS. ... It is a heterodimeric protein consisting of a catalytic subunit calcineurin A containing an active site dinuclear metal center ...
Authorities have noted a potential risk of skin cancer from using topical calcineurin inhibitors but over the years, evidence ... Association Between Topical Calcineurin Inhibitor use and risk of cancer, including lymphoma, keratinocyte carcinoma, and ... In 2006, authorities noted a potential risk of skin cancer from using topical calcineurin inhibitors but over the years the ... There are currently two topical calcineurin inhibitors (TCI) available and indicated for the second-line management of atopic ...
The abstract of this paper is available on the publisher website. For the abstract, go to: this link ...
Calcineurin, a calcium-dependent phosphatase, enhances ca- mediated inactivation of ca current in perfused snail neurons ... Chad, J. and Eckert, R. (1985) Calcineurin, a calcium-dependent phosphatase, enhances ca- mediated inactivation of ca current ... Calcineurin, a calcium-dependent phosphatase, enhances ca- mediated inactivation of ca current in perfused snail neurons ... Calcineurin, a calcium-dependent phosphatase, enhances ca- mediated inactivation of ca current in perfused snail neurons ...
An antiproliferative genetic screening identifies a peptide aptamer that targets calcineurin and up-regulates its activity. ...
"Nerve activity-dependent modulation of calcineurin signaling in adult fast and slow skeletal muscle fibers." J Biol Chem, vol. ... "Nerve activity-dependent modulation of calcineurin signaling in adult fast and slow skeletal muscle fibers." J Biol Chem 276, ... Nerve activity-dependent modulation of calcineurin signaling in adult fast and slow skeletal muscle fibers.. Publication , ... Nerve activity-dependent modulation of calcineurin signaling in adult fast and slow skeletal muscle fibers. J Biol Chem. 2001 ...
... autoinhibitory peptide 148067-21-4. Calcineurin Autoinhibitory Peptide is a selective inhibitor of Ca2+-calmodulin- ... Cyclosporine A is an immunosuppressive agent, binds to the cyclophilin and then inhibits calcineurin with IC50 of 7 nM.. ... Voclosporin is a novel calcineurin inhibitor intended for prevention of organ graft rejection and treatment of lupus nephritis ... Pimecrolimus is an immunomodulating agent of the calcineurin inhibitor class, effective in various inflammatory skin diseases, ...
Calcineurin regulatory subunit B is a unique calcium sensor that regulates calcineurin in both calcium-dependent and calcium- ... Calcineurin-dependent and calcineurin-independent signal transduction pathways activated as part of pancreatic growth. Pancreas ... Interactions of calcineurin A, calcineurin B, and Ca2+. Biochemistry 38: 12481-12489, 1999. PMID: 10493818 ... The role of modulatory calcineurin-interacting proteins in calcineurin signaling. Trends Cardiovasc Med 13: 15-21, 2003. PMID: ...
Calcineurin (CaN) is a highly regulated Ser/Thr protein phosphatase that plays critical roles in learning and memory, cardiac ... Calcineurin (CaN) is a highly regulated Ser/Thr protein phosphatase that plays critical roles in learning and memory, cardiac ... THE DISORDERED REGULATION OF CALCINEURIN: HOW CALMODULIN-INDUCED REGULATORY DOMAIN STRUCTURAL CHANGES LEAD TO THE ACTIVATION OF ... Dunlap, Victoria B., "THE DISORDERED REGULATION OF CALCINEURIN: HOW CALMODULIN-INDUCED REGULATORY DOMAIN STRUCTURAL CHANGES ...
Calcineurin inhibitors. Cyclosporine and tacrolimus are the 2 calcineurin inhibitors currently available for use. These ... Cyclosporine binds cyclophilin in the cytoplasm of the T cell, which then binds calcineurin, a Ca2+ phosphatase, blocking it ... Because mTOR inhibitors work by different mechanisms than calcineurin inhibitors, agents from these two families of drugs can ... The addition of sirolimus can permit dose reduction or even discontinuation of calcineurin therapy. Sirolimus may help prevent ...
Calcineurin is an essential Ca2+-dependent phosphatase. Increased calcineurin activity is associated with α-synuclein (α-syn) ... N2 - Calcineurin is an essential Ca2+-dependent phosphatase. Increased calcineurin activity is associated with α-synuclein (α- ... AB - Calcineurin is an essential Ca2+-dependent phosphatase. Increased calcineurin activity is associated with α-synuclein (α- ... abstract = "Calcineurin is an essential Ca2+-dependent phosphatase. Increased calcineurin activity is associated with α- ...
Calcineurin inhibitors. *cyclosporine (Neoral, Sandimmune, SangCya). *tacrolimus (Astagraf XL, Envarsus XR, Prograf) ...
Topical calcineurin inhibitors. Recommendations 1.5.1.22 to 1.5.1.26 are from NICEs technology appraisal guidance on ... 1.5.1.27 Explain to children with atopic eczema and their parents or carers that they should only apply topical calcineurin ... 1.5.1.28 Do not use topical calcineurin inhibitors under occlusion (bandages and dressings) for treating atopic eczema in ... consider stepping up treatment to topical calcineurin inhibitors. [2007] ...
B. Calcineurin inhibitor toxicity. C. Polyomavirus nephropathy. D. Tubular injury secondary to cryoglobulinemia. E. Diabetic ... These features are suggestive of calcineurin inhibitor toxicity (CNIT) CNIT is dose related, with variable individual ...
We certainly agree with the authors that calcineurin inhibitors (CNIs) should be considered in the treatment of COVID-19.3 Both ...
Click here to learn more about calcineurin inhibitors for LS. ... calcineurin inhibitors or TCIs for short) are. *How calcineurin ... Side Effects and Calcineurin Inhibitors. Burning and Stinging. The primary documented side effect of calcineurin inhibitors are ... Tagscalcineurin inhibitorseducationhealthcareLichen Sclerosusrisk and benefitsTCIstopical calcineurin inhibitorstreatment ... In sum, calcineurin inhibitors are considered by *most* of the medical community to be a safe and effective second-line ...
RCAN binding to calcineurin, a Ca2+/calmodulin-dependent phosphatase, inhibits calcineurin activity, thereby regulating ... RCAN binding to calcineurin, a Ca2+/calmodulin-dependent phosphatase, inhibits calcineurin activity, thereby regulating ... were cryophilic, as were calcineurin gain-of-function mutants wherein calcineurin is constitutively active (Li et al., 2015). ... Rothermel B.A., Vega R.B., and Williams R.S. (2003). The role of modulatory calcineurin-interacting proteins in calcineurin ...
The Human Calcineurin ELISA kit can be used to identify samples from the human species. Calcineurin can also be called CaN, ... Citations of Human Calcineurin ELISA kit. E01C0535 has been referenced in the below publications: ...
Categories Calcineurin S. S.C.M., C.A.O., and R.L.J. aged mice also exhibited elevated expression of SASP genes, including ... Categories Calcineurin (Yu-Chi Cheng) and L. (Yu-Chi Cheng) and L.-W.C. established at < 0.05 and indicated by asterisks in ... Categories Calcineurin At the follow-up check out, NAb titers were independent of comorbidity, Gender and BMI. At the follow- ... Categories Calcineurin accepted for psoriatic arthritis *Not. accepted for psoriatic arthritis *Not. and maintenance of ...
  • Calcineurin is the target of a class of drugs called calcineurin inhibitors, which include ciclosporin, voclosporin, pimecrolimus and tacrolimus. (wikipedia.org)
  • Calcineurin inhibitors are prescribed for adult rheumatoid arthritis (RA) as a single drug or in combination with methotrexate. (wikipedia.org)
  • Calcineurin inhibitors such as tacrolimus are used to suppress the immune system in organ allotransplant recipients to prevent rejection of the transplanted tissue. (wikipedia.org)
  • Topical calcineurin inhibitors are non-steroidal immunomodulators. (rchsd.org)
  • Tacrolimus ointment and Pimecrolimus cream are also known as calcineurin inhibitors , or topical immunomodulators . (what-is-eczema.com)
  • A doctor will only prescribe calcineurin inhibitors when topical steroids are unable to clear a severe flare up. (what-is-eczema.com)
  • Calcineurin inhibitors haven't been used for long periods of times. (what-is-eczema.com)
  • Topical calcineurin inhibitors (TCIs) for atopic dermatitis, a.k.a. eczema, did not seem to up the long-term risk for developing skin cancer, according to a manufacturer-sponsored study. (medpagetoday.com)
  • Exposure to topical calcineurin inhibitors also showed no elevated risk for BCC when compared to those not exposed to either treatment, including TCIs or topical corticosteroids (aHR 1.04, 95% CI 0.91-1.19). (medpagetoday.com)
  • Topical calcineurin inhibitors, including Elidel Cream (pimecrolimus) and Protopic Ointment (tacrolimus), currently carry a boxed warning regarding the potential increased risk for cancer issued by the FDA in January 2006. (medpagetoday.com)
  • We did not find an increased risk of lymphoma in patients treated with topical calcineurin inhibitors. (rti.org)
  • In 2006, authorities noted a potential risk of skin cancer from using topical calcineurin inhibitors but over the years the evidence suggests that these risks are very small. (hospitalhealthcare.com)
  • There are currently two topical calcineurin inhibitors (TCI) available and indicated for the second-line management of atopic eczema: pimecrolimus and tacrolimus. (hospitalhealthcare.com)
  • We certainly agree with the authors that calcineurin inhibitors (CNIs) should be considered in the treatment of COVID-19. (reumatologiaclinica.org)
  • We are continuing our lichen sclerosus treatment series today by looking at topical calcineurin inhibitors. (lssupportnetwork.org)
  • I draw on the medical literature to share what you need to know about calcineurin inhibitors and lichen sclerosus. (lssupportnetwork.org)
  • What the Heck are Topical Calcineurin Inhibitors (TCIs)? (lssupportnetwork.org)
  • Therefore, because calcineurin inhibitors can suppress immune system activity, TCIs have been studied and used to treat many immune-mediated skin conditions, such as lichen sclerosus (Corazza et al. (lssupportnetwork.org)
  • The main calcineurin inhibitors used for lichen sclerosus are Pimecrolimus and Tacrolimus. (lssupportnetwork.org)
  • Overall, the studies are pretty promising and show that topical calcineurin inhibitors can be a good option for folks (Corazza et al. (lssupportnetwork.org)
  • The primary documented side effect of calcineurin inhibitors are stinging and burning. (lssupportnetwork.org)
  • I have heard mixed things about calcineurin inhibitors from folks using them in the LS community. (lssupportnetwork.org)
  • How should we use calcineurin inhibitors in myasthenia gravis? (elsevierpure.com)
  • Calcineurin inhibitors are approved for the treatment of myasthenia gravis in Japan. (elsevierpure.com)
  • described the use of calcineurin inhibitors and outcomes of myasthenia gravis in Japan using the data of a multicenter survey. (elsevierpure.com)
  • According to the result, they argue that calcineurin inhibitors should be given more aggressively to late-onset myasthenia gravis patients and early-stage disease. (elsevierpure.com)
  • Dive into the research topics of 'How should we use calcineurin inhibitors in myasthenia gravis? (elsevierpure.com)
  • Kidney transplantation remains limited by toxicities of calcineurin inhibitors (CNIs) and steroids. (atcmeetingabstracts.com)
  • Background : Calcineurin inhibitors (CNI: cyclosporine, tacrolimus) are majorimmunosuppressants used in kidney transplant (KT) patients.Nephrotoxicity is an important side effect of CNI. (chula.ac.th)
  • Topical calcineurin inhibitors (TCI) reduce eczema flare-ups by preventing the part of the immune system that causes them from becoming active. (allaboutcareers.com)
  • Live attenuated vaccines generally should be avoided in immunocompromised travelers, including those taking antimetabolites, calcineurin inhibitors, cytotoxic agents, immunomodulators, and high-dose steroids (see Table 3-04 ). (cdc.gov)
  • Background: Calcineurin inhibitors (CNIs) (Tacrolimus and cyclosporine [CSA]) are immunosuppressive drugs that are administrated to prevent liver rejection after liver transplantation. (asiapharmaceutics.info)
  • Tacrolimus is in a class of medications called topical calcineurin inhibitors. (medlineplus.gov)
  • Calcineurin can be inhibited with Tacrolimus through the recruitment and inhibition of the 12-kDa cis-trans proline isomerase FK506-binding protein (FKBP12).Whether calcineurin/ FKBP12 represents a native physiologically relevant assembly that occurs in the absence of pharmacological perturbation has remained elusive. (psu.edu)
  • We leveraged α-syn as a model to interrogate whether FKBP12 plays a role in regulating calcineurin activity in the absence of Tacrolimus.We showthat FKBP12 profoundly affects the calcineurindependent phosphoproteome, promoting the dephosphorylation of a subset of proteins that contributes to α-syn toxicity. (psu.edu)
  • Using a rat model of PD, partial elimination of the functional interaction between FKBP12 and calcineurin,with low doses of the Food and Drug Administration (FDA)-approved compound Tacrolimus, blocks calcineurin's activity toward those proteins and protects against the toxic hallmarks of α-syn pathology. (psu.edu)
  • This is a post-hoc analysis from a clinical trial to study the area under curve (AUC) and the area under effect (AUE) profiles of calcineurin inhibition after tacrolimus administration in twenty-five renal transplant patients. (frontiersin.org)
  • Whole blood and intracellular tacrolimus concentrations and calcineurin activity were measured by UHPLC-MS/MS. (frontiersin.org)
  • Calcineurin (CaN) is a calcium and calmodulin dependent serine/threonine protein phosphatase (also known as protein phosphatase 3, and calcium-dependent serine-threonine phosphatase). (wikipedia.org)
  • The activity of the protein phosphatase calcineurin (CN) is regulated by an autoinhibition mechanism wherein several domains from its catalytic A subunit, including the calmodulin binding domain (CaMBD), block access to its active site. (rcsb.org)
  • Forms a FK-506 binding protein 12 (FKBP12) - Ascomycin -Calcineurin complex. (abcam.com)
  • Calcineurin (PP2B) is a calcium/calmodulin dependent Ser/Thr protein phosphatase that is expressed at high levels in the CNS. (sysy.com)
  • It is a heterodimeric protein consisting of a catalytic subunit calcineurin A containing an active site dinuclear metal center, and a tightly associated, myristoylated, Ca 2+ -binding subunit called calcineurin B. Calcineurin is involved in many cellular processes and Ca 2+ -dependent signal transduction pathways. (sysy.com)
  • Calcineurin Autoinhibitory Peptide is a selective inhibitor of Ca2+-calmodulin-dependent protein phosphatase (calcineurin) with IC50 ~ 10 μM. (csnpharm.cn)
  • Calcineurin (CN) is a Ca 2+ /calmodulin dependent serine/threonine protein phosphatase first identified in brain and also known as protein phosphatase 2B (PP2B). (pancreapedia.org)
  • Calcineurin (CaN) is a highly regulated Ser/Thr protein phosphatase that plays critical roles in learning and memory, cardiac development and function, and immune system activation. (uky.edu)
  • Increased calcineurin activity is associated with α-synuclein (α-syn) toxicity, a protein implicated in Parkinson's Disease (PD) and other neurodegenerative diseases. (psu.edu)
  • RCAN1 is upregulated by stress factors, such as protein aggregates, elevated intracellular calcium, oxidative stress, and glucocorticoid, prevents excess and dangerous over-activation of calcineurin. (molcells.org)
  • Calcineurin can also be called CaN, Calcineurin, protein phosphatase 3, calcium-dependent serine-threonine phosphatase. (elisakit.cc)
  • Immunohistochemical and biochemical investigations of Ca2+/calmodulin-dependent protein kinase II(CaM kinase II) and protein phosphatase (calcineurin) after transient forebrain ischemia demonstrated that the activity of CaM kinase II was decreased in the CA1 region of the hippocampus early (6-12 hours) after ischemia. (nih.gov)
  • Launch Calcineurin (May) is really a calcium-dependent serine/threonine phosphatase that regulates ion stations cytoskeletal protein and transcription elements (Klee et al. (conferencedequebec.org)
  • Finally, we show that the calcium -activated protein phosphatase calcineurin dephosphorylates Hoxb13 at serine -204, resulting in its nuclear localization and cell cycle arrest . (bvsalud.org)
  • A CALCIUM and CALMODULIN-dependent serine/threonine protein phosphatase that is composed of the calcineurin A catalytic subunit and the calcineurin B regulatory subunit. (bvsalud.org)
  • Cyclosporine is a calcineurin inhibitor. (medscape.com)
  • Cyclosporine A is an immunosuppressive agent, binds to the cyclophilin and then inhibits calcineurin with IC50 of 7 nM. (csnpharm.cn)
  • RCAN binding to calcineurin, a Ca 2+ /calmodulin-dependent phosphatase, inhibits calcineurin activity, thereby regulating different physiological events via dephosphorylation of important substrates. (molcells.org)
  • FK-506, which also inhibits calcineurin, was applied at a concentration of 0.1 μM, and promoted CAP amplitude recovery to 82.6±5.0% of control after hypoxic injury and reoxygenation of dorsal column white matter. (nebraska.edu)
  • abstract = "Calcineurin is an essential Ca2+-dependent phosphatase. (psu.edu)
  • A hypothesized mechanism of action for TCIs increasing KC risk includes a direct effect of calcineurin inhibition on DNA repair and apoptosis, which could influence keratinocyte carcinogenesis," Asgari and colleagues explained. (medpagetoday.com)
  • Aggregation, but not dispersion, is inhibited by okadaic acid at concentrations consistent with an inhibition of calcineurin activity. (silverchair.com)
  • Inhibition of calcineurin with cyclosporin A prevented increases in heart mass and myocyte size but was associated with an intermediate APD. (elsevierpure.com)
  • We harnessed unbiased systematic approaches for SLiM discovery to elucidate the regulatory network of calcineurin (CN)/PP2B, the Ca 2+ -activated phosphatase that recognizes LxVP and PxIxIT motifs. (nih.gov)
  • Calcineurin/PP2B inhibitor. (abcam.com)
  • Calcineurin/PP2B inhibitor (IC 50 = 49 nM). (abcam.com)
  • Calcineurin (Cn) is a Ca 2+ /calmodulin (CaM)-dependent serine/threonine phosphatase first identified in extracts of mammalian brain (68, 94). (pancreapedia.org)
  • A serine-threonine phosphatase, calcineurin (CN), subunit A, a isoform (Ppp3ca), was one of the seven candidates in the cdm region that was narrowed from 5.6 to 2.0 Mb on mouse chromosome 3. (cdc.gov)
  • Calcineurin is a heterodimer of a 61-kD calmodulin-binding catalytic subunit, calcineurin A and a 19-kD Ca2+-binding regulatory subunit, calcineurin B. There are three isozymes of the catalytic subunit, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two isoforms of the regulatory, also encoded by separate genes (PPP3R1, PPP3R2). (wikipedia.org)
  • When an antigen-presenting cell interacts with a T cell receptor on T cells, there is an increase in the cytoplasmic level of calcium, which activates calcineurin by binding a regulatory subunit and activating calmodulin binding. (wikipedia.org)
  • Through its regulation of calcineurin RCAN1 has been implicated in fetal cardiac and vasculature development, angiogenesis, and cardiac hypertrophy. (uky.edu)
  • Potential targets of therapeutic intervention include the cytoplasmic phosphatase calcineurin and small guanosine triphosphate-binding proteins, such as Rac1 and RhoA, all of which have been implicated in maladaptive hypertrophy. (tamu.edu)
  • The hypertrophy-associated increase in I Ca,L and the accelerated recovery from inactivation were blocked by cyclosporin A. Conclusions - These data reveal regional variation in the electrophysiological response within the left ventricle by way of a mechanism involving upregulated Ca 2+ current and calcineurin. (elsevierpure.com)
  • Thus, FKBP12 can endogenously regulate calcineurin activity with therapeutic implications for the treatment of PD. (psu.edu)
  • RCAN1 can both stimulate and inhibit calclfleurin depending on its cellular concentration and phosphorylation state, however the strnctural mechanism by whiCh RCAN1 can differentially regulate calcineurin is unknown. (uky.edu)
  • We show that TPC-released Ca2+ rapidly activates calcineurin, which in turn dephosphorylates and activates the GTPase dynamin-2. (ox.ac.uk)
  • Regulator of calcineurin 1 (RCAN1) facilitates neural apoptosis through caspase-3 activation. (bvsalud.org)
  • Histological characteristics of calcineurin inhibitor toxicity : there is no such thing as specificity! (unibas.ch)
  • FK506, a calcineurin inhibitor, prevents cadmium-induced testicular toxicity in mice. (cdc.gov)
  • At the Albany Medical Center, we have a long-term experience, mean follow-up of 75 months, in 50 renal transplant recipients treated with maintenance sirolimus, prednisone and a calcineurin-inhibitor sparing immunosuppressive regimen. (utmb.edu)
  • Sirolimus is an effective maintenance immunosuppressive agent that safely allows for a reduction in calcineurin-inhibitor dosing. (utmb.edu)
  • Among nearly 100,000 adults with atopic dermatitis, those treated with a topical calcineurin inhibitor did not see a significantly higher risk for keratinocyte carcinoma (KC) compared with those who received topical corticosteroids (adjusted hazard ratio 1.02, 95% CI 0.93-1.13), according to Maryam Asgari, MD, MPH, of Massachusetts General Hospital in Boston, and colleagues. (medpagetoday.com)
  • A calcineurin-Hoxb13 axis regulates growth mode of mammalian cardiomyocytes. (bvsalud.org)
  • These developments suggest that besides significant contributions to DS pathologies and calcineurin regulation, RCAN is an important participant across physiological systems, suggesting it as a favorable therapeutic target. (molcells.org)
  • Voclosporin is a novel calcineurin inhibitor intended for prevention of organ graft rejection and treatment of lupus nephritis. (csnpharm.cn)
  • Calcineurin activates nuclear factor of activated T cell cytoplasmic (NFATc), a transcription factor, by dephosphorylating it. (wikipedia.org)
  • We show that dephosphorylation of NFATc1, MEF2A, and MEF2D transcription factors by calcineurin in all muscle types is dependent on nerve activity and positively correlated with muscle usage under normal weightbearing conditions. (duke.edu)
  • With increased nerve-mediated activity, calcineurin dephosphorylation of these targets was found to be potentiated in a way that paralleled the higher muscle activation profiles associated with functional overload or nerve electrical stimulation conditions. (duke.edu)
  • We also establish that muscle activity must be sustained above native levels for calcineurin-dependent dephosphorylation of MEF2A and MEF2D to be transduced into an increase in MEF2 transcriptional function, suggesting that calcineurin cooperates with other activity-linked events to signal via these proteins. (duke.edu)
  • By inhibiting the enzyme calcineurin in immune cells, they interfere with the production of a number of inflammatory substances that contribute to skin inflammation in atopic dermatitis. (rchsd.org)
  • Scholars@Duke publication: Nerve activity-dependent modulation of calcineurin signaling in adult fast and slow skeletal muscle fibers. (duke.edu)
  • Purpose: In the present study we examined the role of Cyclosporin A (CsA), FK-506 and rapamycin in modulating the effects of Ca 2+ influx through their interactions with immunophilins and specifically the end result of calcineurin modulation. (nebraska.edu)
  • This study tested the hypothesis that calcineurin signaling is modulated in skeletal muscle cells by fluctuations in nerve-mediated activity. (duke.edu)
  • Calcineurin (CaN) activation is critically mixed up in regulation of backbone morphology in response to oligomeric amyloid β (Aβ) in addition to in synaptic plasticity in normal memory but zero existing techniques may monitor the spatiotemporal design of May activity. (conferencedequebec.org)
  • Finally, examination of individual fiber responses to overload and nerve electrical stimulation revealed that calcineurin-MEF2 signaling occurs in all fiber types but most readily in fibers that are normally least active (i.e. those expressing IIx and IIb myosin heavy chain (MHC)), suggesting that signaling via this phosphatase is also dependent upon the activation history of the muscle cell. (duke.edu)
  • Calcineurin is an essential Ca 2+ -dependent phosphatase. (psu.edu)
  • Mediates calcineurin-dependent activation of NF-AT, as well as activation of NF-kappa-b and AP-1. (lu.se)
  • Calcineurin induces transcription factors (NFATs) that are important in the transcription of IL-2 genes. (wikipedia.org)
  • 3 months) acute rejection episodes developed despite calcineurin-inhibitor dose minimization. (utmb.edu)
  • Regulation of organelle transport in melanophores by calcineurin. (silverchair.com)
  • In this study, we examined the molecular interplay among these molecules, finding that Rho family guanosine triphosphatase signaling occurs either downstream of calcineurin or as a required, parallel pathway. (tamu.edu)
  • Relationship between changes of calcineurin inhibitorlevels and serum " by S Hasatsri, A Chaiprasert et al. (chula.ac.th)
  • An experiment with genetically-altered mice that could not produce calcineurin showed similar symptoms as in humans with schizophrenia: impairment in working memory, attention deficits, aberrant social behavior, and several other abnormalities characteristic of schizophrenia. (wikipedia.org)