Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Okadaic acid is the main toxin responsible for the natural phenomena known as diarrheic shellfish poisoning (DSP). This toxin is a tumor promoter C38 polyether fatty acid that contains acidic and hydrophobic moieties and is cyclic. Okadaic acid is a potent inhibitor of important classes of protein serine/threonine phosphatases such as protein phosphatase 1 and 2A. The toxin binds in a hydrophobic groove adjacent to the active site of the protein phosphatases and interacts with basic residues within the active site. Therefore okadaic acid causes increases in phosphorylation of proteins that affect a diverse array of cellular processes. For instance, this toxin modulates metabolic parameters in intact cells. In this sense it stimulates lipolysis, and inhibits fatty acid synthesis in adipocytes however increases glucose output and gluconeogenesis in hepatocytes. Additionally, okadaic acid reaches cytotoxic concentrations in the intestinal tissues in accordance with the diarrhea. Recent studies suggested that toxic effects of okadaic acid might be related to modification of nutrients, ionic and water absorption across the small intestine presumably by altering the transporter system. The subject of this review is limited to the effect of okadaic acid on glucose regulation and its cellular as well as clinical implications.
...
PMID:Effect of okadaic acid on glucose regulation. 1572 Feb 90

Two leucine aminopeptidase M inhibitors, cyanostatin A and B, were isolated from cyanobacterial water blooms at Loch Rescobie in Scotland, and specifically from a Microcystis species. Both inhibitors were lipopeptides containing 3-amino-2-hydroxydecanoic acid and weak inhibitors of protein phosphatase (PP2A). Both strongly inhibited the activity of leucine aminopeptidase M with IC50 values of 40 and 12 ng/ml, respectively.
...
PMID:Leucine aminopeptidase M inhibitors, cyanostatin A and B, isolated from cyanobacterial water blooms in Scotland. 1572 46

Arsenic present in drinking water and mining environments in some areas has been associated with an increased rate of skin and internal cancers. Contrary to the epidemiological evidence in humans, arsenic does not induce cancer in animal models, but is able to enhance the mutagenicity of other agents. In order to achieve a better understanding of the interaction between arsenic and ionising radiation, an investigation was conducted to detect differences at the proteome level of human TK6 lymphoblastoid cells exposed to these agents. Cells were exposed to either a single dose of 1-Gy 137Cs-gamma-rays or to 1 microM arsenite (As(III)) or to both agents in combination. Two-dimensional (2D) electrophoresis and matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF) were employed for the screening and identification of proteins, respectively. It proved possible to identify seven proteins with significantly affected abundance, three of which showed increased levels and the remaining four showed decreased levels under at least one of the exposure conditions. Following arsenite treatment or irradiation, a significant increase compared with that of the control was observed for glutathione (GSH) transferase omega 1 and proteasome subunit beta type 4 precursor. The combined exposure did not result in an induction of the enzymes. The expression of electron-transfer flavoprotein subunit alpha was found to be enhanced under all three-exposure conditions. Ubiquinol-cytochrome C reductase complex core protein I, adenine phosphoribosyl transferase and endoplasmic reticulum protein hERp29 showed decreased levels after irradiation or arsenite treatment, but not after the combined exposure. The level of serine/threonine protein phosphatase 1 alpha decreased with all treatments. The main conclusions are that both arsenite and gamma-radiation influence the levels of several proteins involved in major metabolic and regulatory pathways, either directly or by triggering the defence mechanisms of the cell. The combined effect of both exposures on the level of some essential proteins such as glutathione transferase, proteasome or serine/threonine phosphatase may contribute to the co-carcinogenic effect of arsenic.
...
PMID:Combined effects of gamma radiation and arsenite on the proteome of human TK6 lymphoblastoid cells. 1572 13

Concern regarding the presence of microcystins in drinking water and their possible contamination in food (e.g., salad vegetables, fish, shellfish) has resulted in the need for reliable methods for the detection and accurate quantification of this class of toxins. Currently, routine analysis of microcystins is most commonly carried out using high-performance liquid chromatography with photodiode array detection (HPLC-PDA), although more sensitive biological assays such as antibody-based ELISAs and protein phosphatase inhibition assays have also proven useful. However, many of these methods have been hindered by the availability of a wide range of purified microcystins. Although over 60 variants have now been reported, only a very small number are commercially available and calibrated standards are not yet obtainable. This has led to the common practice of reporting microcystin-LR equivalence regardless of which variant is present. The increased availability of HPLC with online mass spectral analysis (HPLC-MS) may facilitate more accurate detection of toxin variants but as several microcystins share the same molecular mass, definitive identification can be difficult. A further difficulty in analyzing microcystins is the requirement for sample processing before analysis. Solid phase extraction (SPE) is typically used to enrich environmental concentrations of microcystins, or to eliminate contaminants from complex samples such as animal and plant tissues. Recently, new technologies employing recombinant antibodies and molecularly imprinted polymers have been exploited to develop assays and biosensors for microcystins. These novel detection systems are highly sensitive, often do not require sample processing, and offer a simpler, less expensive alternative to analytical techniques. They have also been successfully employed in solid phase extraction formats for the concentration and clean up of environmental samples before HPLC analysis.
...
PMID:Detection of the cyanobacterial hepatotoxins microcystins. 1573 76

Toxic cyanobacteria in aquatic environments have been implicated in many poisoning incidents of livestock, wildlife, and domestic animals. Microcystins (MCYSTs) in water supplies represent a risk to public health. This work investigated the effect of water composition on the quantitation and biological activity of MCYSTs analyzed by different methods (HPLC, ELISA, and protein phosphatase 1 inhibition assay). Different MCYST concentrations were added to deionized water and quantified, confirming the efficiency of these analytical methods. MCYST concentrations diluted in drinking water had reduced detection by all methods tested. The drinking water used contained a free chlorine concentration of 2.5 mg/L and an Fe concentration of 0.45 mg/L, and the conductivity was 69.8 microS cm(-1), whereas in deionized water, free chlorine and Fe were not detectable, and the conductivity was 1.6 microS cm(-1). Drinking water also interfered with the biological activity of MYCSTs, as these toxins showed reduced protein phosphatase-1 inhibition. A free chlorine concentration of 2.5 mg/L in deionized water was completely effective in preventing any detection of 10 microg/L of added MCYSTs. Fe and Al ions also were very effective in reducing MCYST detection. The chemical composition of drinking water thus affected MCYST detection, indicating a significant reduction in quantitation of this molecule either because of its decomposition or through complexation with metal ions.
...
PMID:Influence of drinking water composition on quantitation and biological activity of dissolved microcystin (cyanotoxin). 1579 28

Oneida Lake, northeast of Syracuse, New York, in the United States, is a shallow eutrophic lake with a well-established toxic cyanobacterial population. Samples for DNA, toxin, and phycological analyses were collected from six stations throughout the summers of 2002 (78 samples) and 2003 (95 samples). DNA was amplified by PCR using primer sets specific to the nonribosomal microcystin synthetase complex (mcyB and mcyD). PCR analysis in 2002 indicated that the microcystin genes were present in the water column from mid-June through October, as 88% of the samples tested positive for mcyB and 79% of the samples tested positive for mcyD. In both years the onset of microcystin production was detected as early as mid-July by the protein phosphatase inhibition assay, reaching a maximum in 2002 of 2.9 microg L(-1) and in 2003 of 3.4 microg L(-1). Beginning in mid- to late August of both years the microcystin level at all six stations was in excess of the World Health Organization (WHO) advisory level of 1.0 microg L(-1). In the present study we compared microcystin occurrence and potential production at the six stations using protein phosphatase inhibition assay, high-performance liquid chromatography, and polymerase chain reaction analyses.
...
PMID:Seasonal production and molecular characterization of microcystins in Oneida Lake, New York, USA. 1589 72

Cyanotoxins, particularly microcystins (MCs), have been shown to be a hazard to human health. MCs accumulate in aquatic organisms probably as a result of irreversible binding to liver protein phosphatases. The aim of this study was to describe the recovery of MC from fish liver using various detection methods, with MC-LR as the representative congener. These findings are discussed in conjunction with the current procedures and limit values used for human risk assessment. Following incubation of liver homogenates with various MC-LR concentrations, the homogenates were extracted by a water/methanol/butanol mixture via different treatments and subsequently analyzed via the colorimetric protein phosphatase inhibition assay (cPPA), HPLC, and anti-Adda ELISA. Detection via cPPA appeared to yield the highest recovery of MC-LR, although the presence of unspecific background may have resulted in overestimation of the true recovery. The recoveries determined via HPLC and anti-Adda ELISA were comparable to each other. The limits of detection were 0.01-2.4 microg MC-LR/g liver tissue, depending on the method used. Maximum MC-LR recovery from samples incubated with 10 and 100 microg MC-LR/g ranged between 44% and 101%. Recovery from samples incubated with 1 microg MC-LR/g liver tissue was below 3%. Lower recovery is assumed to result from irreversible, covalent MC protein binding, as confirmed by Western blotting of liver homogenates with anti-Adda immunoprobing. The results demonstrate that further investigation of and improvement in routinely applied MC methods for fish tissue and/or food analyses are needed for a reliable risk assessment.
...
PMID:Recovery of MC-LR in fish liver tissue. 1600 63

Cyanobacterial toxins (CBTs), produced by glue-green algae, are one of the most common naturally occurring toxins found in potable waters. The microcystin family of CBTs present in drinking water sources poses a considerable threat to human health. In this study, we have demonstrated that ultrasonic irradiation at 640 kHz leads to rapid degradation of microcystin-LR (MC-LR). Degradation of MC-LR present in the crude cyanobacterial extracts containing cell constituents has been studied with ultrasound under a variety of conditions. The degradation of MC-LR was demonstrated over a concentration range from 0.03 to 3.0 microM. Hydroxyl radical scavenger experiments indicate that hydroxyl radical is responsible for a significant fraction of the observed degradation, but other processes (hydrolysis/ pyrolysis) are also important. Analysis of the protein phosphatase inhibition activity of the reaction products indicates that the products from ultrasonic degradation of MC-LR do not exhibit any measurable biological activity. The results demonstrate that ultrasonic irradiation maybe an effective and practical method for the detoxification of microcystins from drinking water.
...
PMID:Ultrasonically induced degradation and detoxification of microcystin-LR (cyanobacterial toxin). 1617 96

Growth was investigated over 16 d in juvenile common carp (Cyprinus carpio L.) held in either static water (tank rested, TR16) or exercised in a flume at 2.5-3.2 body lengths s-1 for 18 h a day (exercised, E16). Relative to the start of the experiment (TR0), the TR16 group showed a 31% increase in body mass (specific growth rate, 1.57% d-1), whereas there was no net change in the E16 group. There was, however, a significant exercise-induced hypertrophy of slow muscle fibres with average fibre cross-sectional area (FCSA) increasing by 35% in the E16 group, compared with 11% in the TR16 group. In contrast, FCSA of fast muscle fibres increased by 34% in the TR16 group compared to just 18% in the E16 group. The relative concentrations and subcellular localisation of proteins hypothesised to play a role in the regulation of muscle growth were measured. MyoD concentration was similar in the TR0, TR16 and E16 groups in both slow and fast muscle. However, there was a small (5%-10%) but statistically significant increase in nuclear localisation of MyoD in those groups showing a significant increase in FCSA over the time course of the experiment. PCNA concentration was 31% and 12% higher in the TR16 than in either the TR0 or E16 groups for slow and fast muscle, respectively. Exercise resulted in a approximately 10% increase in nuclear factor of T-cells (NFAT2) concentration in slow muscle but no change in NFAT2 localisation. Calcineurin B concentration was similar in tank rested and exercised groups. The results do not support a major role for the calcineurin-signalling pathway in the regulation of muscle hypertrophy in the common carp.
...
PMID:The molecular regulation of exercised-induced muscle fibre hypertrophy in the common carp: expression of MyoD, PCNA and components of the calcineurin-signalling pathway. 1618 6

The microcystins and nodularins are tumour promoting hepatotoxins that are responsible for global adverse human health effects and wildlife fatalities in countries where drinking water supplies contain cyanobacteria. The toxins function by inhibiting broad specificity Ser/Thr protein phosphatases in the host cells, thereby disrupting signal transduction pathways. A previous crystal structure of a microcystin bound to the catalytic subunit of protein phosphatase-1 (PP-1c) showed distinct changes in the active site region when compared with protein phosphatase-1 structures bound to other toxins. We have elucidated the crystal structures of the cyanotoxins, motuporin (nodularin-V) and dihydromicrocystin-LA bound to human protein phosphatase-1c (gamma isoform). The atomic structures of these complexes reveal the structural basis for inhibition of protein phosphatases by these toxins. Comparisons of the structures of the cyanobacterial toxin:phosphatase complexes explain the biochemical mechanism by which microcystins but not nodularins permanently modify their protein phosphatase targets by covalent addition to an active site cysteine residue.
...
PMID:Crystal structures of protein phosphatase-1 bound to motuporin and dihydromicrocystin-LA: elucidation of the mechanism of enzyme inhibition by cyanobacterial toxins. 1634 32


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---