Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Modulation of the expression of the protein phosphatase-1 (PP1) glycogen-targeting subunit PTG exerts profound effects on cellular glycogen metabolism in vitro and in vivo. PTG contains three distinct binding domains for glycogen, PP1, and a common site for glycogen synthase and phosphorylase. The impact of disrupting the PP1-binding domain on PTG function was examined in 3T3-L1 adipocytes. A full-length PTG mutant was generated as an adenoviral construct in which the valine and phenylalanine residues in the conserved PP1-binding domain were mutated to alanine (PTG-VF). Infection of fully differentiated 3T3-L1 adipocytes with the PTG-VF adenovirus reduced glycogen stores by over 50%. In vitro, PTG-VF competitively interfered with wild-type PTG action, suggesting that the mutant construct acted as a dominant-negative molecule. The reduction in cellular glycogen storage was due to a significantly increased rate of glycogen turnover. Interestingly, acute basal and insulin-stimulated glucose uptake and glycogen synthesis rates were enhanced in PTG-VF expressing cells vs. control 3T3-L1 adipocytes, likely as a compensatory response to the loss of glycogen stores. These results indicate that the mutation of the PP1-binding domain on PTG resulted in the generation of a dominant-negative molecule that impeded endogenous PTG action and reduced cellular glycogen levels, through enhancement of glycogenolysis rather than impairment of glycogen synthesis.
Obesity (Silver Spring) 2010 Oct
PMID:Generation of a dominant-negative glycogen targeting subunit for protein phosphatase-1. 2020 31

At least three Ca(2+)-binding proteins were detected in rat cortex by (45)Ca(2+) autoradiography of two-dimensional electrophoretograms. The identities of two of these Ca(2+)-binding proteins were determined to be calmodulin and the B subunit of calcineurin. The identification was based upon the following criteria: (1) co-localization on polyacrylamide gels with the appropriate purified proteins, (2) staining of nitrocellulose blots with specific antisera for calmodulin and calcineurin and (3) ability to bind Ca(2+). This information is useful in that it identifies two major brain proteins visible on silver-stained two-dimensional polyacrylamide gels. In addition, this data reveals the location of an unidentified Ca(2+)-binding protein of molecular weight ? 18,000 Da and pI 5.4 on these gels.
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PMID:Localization of Ca(2+)-binding proteins of rat cortex on two-dimensional gels-I. Identification of calmodulin and the b subunit of calcineurin. 2050 Dec 24

Although clinical trials for new drugs are often limited in children because of safety concerns or restrictions, new therapies or novel strategies with old drugs have recently expanded dermatologic armamentarium for pediatric patients. Oral propranolol is currently the first choice in the treatment of alarming infantile hemangiomas. In atopic dermatitis, proactive strategy with topical calcineurin inhibitors can safely prevent disease exacerbation. Tacrolimus, in particular, is also useful for the treatment of vitiligo occurring in sensitive areas such as the eyelids. Among biologic drugs, use of etanercept is safe and efficient in children and adolescents with moderate-to-severe plaque psoriasis. Engineered tissues with special antimicrobial properties (silver-coated fabrics or engineered silk) are now used to treat eczema and fungal diseases in children. In athlete's foot, the use of 5-finger socks can also be helpful.
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PMID:Innovative therapeutics in pediatric dermatology. 2051 Jul 70

Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes cognitive and behavioral deterioration in the elderly. Neurofibrillary tangles (NFTs) are one of the pathological hallmarks of AD that has been shown to correlate positively with the severity of dementia in the neocortex of AD patients. In an attempt to characterize an in vivo AD tauopathy model, okadaic acid (OA), a protein phosphatase inhibitor, was microinfused into the right lateral dorsal hippocampus area of ovariectomized adult rat. Cognitive deficiency was seen in OA-treated rats without a change in motor function. Both silver staining and immunohistochemistry staining revealed that OA treatment induces NFTs-like conformational changes in both the cortex and hippocampus. Phosphorylated tau as well as cyclin-dependent kinase 5 (cdk5) and its coactivator, p25, were significantly increased in these regions of the brain. Oxidative stress was also increased with OA treatment as measured by protein carbonylation and lipid peroxidation. These data suggest that the unilateral microinfusion of OA into the dorsal hippocampus causes cognitive deficiency, NFTs-like pathological changes, and oxidative stress as seen in AD pathology via tau hyperphosphorylation caused by inhibition of protein phosphatases.
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PMID:An okadaic acid-induced model of tauopathy and cognitive deficiency. 2080 17

The use of nanoparticles in foods, materials, and clinical treatments has increased dramatically in the past decade. Because of the possibility of human exposure to nanoparticles, there is an urgent need to investigate the molecular mechanisms underlying the cellular responses that might be triggered. Such information is necessary to assess potential health risks arising from the use of nanoparticles, and for developing new formulations of next generation nanoparticles for clinical treatments. Using mass spectrometry-based proteomic technologies and complementary techniques (e.g., Western blotting and confocal laser scanning microscopy), we present insights into the silver nanoparticle-protein interaction in the human LoVo cell line. Our data indicate that some unique cellular processes are driven by the size. The 100 nm nanoparticles exerted indirect effects via serine/threonine protein kinase (PAK), mitogen-activated protein kinase (MAPK), and phosphatase 2A pathways, and the 20 nm nanoparticles induced direct effects on cellular stress, including generation of reactive oxygen species and protein carbonylation. In addition, we report that proteins involved in SUMOylation were up-regulated after exposure to 20 nm silver nanoparticles. These results were further substantiated by the observation of silver nanoparticles entering the cells; however, data indicate that this was determined by the size of the nanoparticles, since 20 nm particles entered the cells while 100 nm particles did not.
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PMID:Insights into the cellular response triggered by silver nanoparticles using quantitative proteomics. 2451 82

Microcystins, the lethal cyanotoxins from Microcystis aeruginosa, can inhibit the activity of protein phosphatase and promote liver tumors. Herein, a dual-modal split-type immunosensor was constructed to detect microcystin-LR (MC-LR), based on the photocurrent change of CdS/ZnO hollow nanorod arrays (HNRs) and the blue shift of the surface plasmon resonance peak from Au nanobipyramids@Ag. By using mesoporous silica nanospheres as the carrier to immobilize secondary antibody and DNA primer, a hybridization chain reaction was adopted to capture alkaline phosphatase, while its catalytic reaction product, ascorbic acid, exhibited dual functions. The detailed mechanism was investigated, showing that ascorbic acid can not only act as the electron donor to capture the holes in CdS/ZnO-HNRs, leading to the increase photocurrent, but also as the reductant to form silver shells on Au nanobipyramids, generating multiply vivid color variations and blue shifts. Compared with the traditional photoelectrochemical immunosensor or colorimetric method for MC-LR, a more accurate and reliable result can be obtained, due to different mechanisms and independent signal transduction. Therefore, this work can not only propose a new dual-modal immunosensor for MC-LR detection but also provide innovative inspiration for constructing sensitive, accurate, and visual analysis for toxins.
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PMID:Dual-Modal Split-Type Immunosensor for Sensitive Detection of Microcystin-LR: Enzyme-Induced Photoelectrochemistry and Colorimetry. 2998 99

Invasive fungal infections especially in immunocompromised patients represent a dominating cause of mortality. The most commonly used antifungal agents can be divided into three broad categories, including triazoles, echinocandins and polyenes. Antifungal resistance is on the increase, posing a growing threat to the stewardship of immunocompromised patients with fungal infections. The paucity of currently available antifungals leads to the rapid emergence of drug resistance and thus aggravates the refractoriness of invasive fungal infections. Therefore, deep exploration into mechanisms of drug resistance and search for new antifungal targets are required. This review highlights the therapeutic strategies targeting Hsp90, calcineurin, trehalose biosynthesis and sphingolipids biosynthesis, in an attempt to provide clinical evidence for overcoming drug resistance and to form the rationale for combination therapy of conventional antifungals and agents with novel mechanisms of action. What's more, this review also gives a concise introduction of three new-fashioned antifungals, including carboxymethyl chitosan, silver nanoparticles and chromogranin A-N46.
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PMID:An insight into new strategies to combat antifungal drug resistance. 3046 12


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