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

Oral dosing of rats with cyclohexanol and methylcyclohexanols resulted in the inhibition of hepatic HMGCoA reductase. Neither cyclohexane or cyclohexane diols exerted any effects. Inhibition was not due to alcohol dehydrogenase mediated changes in redox state since 3,3',5-trimethylcyclohexanol (TMC), a non substrate for alcohol dehydrogenase, was a potent inhibitor of HMGCoA reductase. Following a single dose of TMC there was no alteration in total hepatic HMGCoA reductase activity for more than 6 hr after which the enzyme activity was depressed in a dose-dependent manner. The normal diurnal rhythm of HMGCoA reductase was reduced in amplitude following TMC administration but the phase was unaltered and the t 1/2 for activity decay following the peak of activity was unaffected. Prior to the inhibitory effect of a TMC dose becoming apparent in total HMGCoA reductase activity we found that the expressed activity of the enzyme (after isolation in F- medium to suppress endogenous protein phosphatase) was depressed by 43%. The inhibitory effect of TMC on total HMGCoA reductase activity seen 8 hr or more after dosing was reflected by inhibition of sterol synthesis in liver measured in vivo after [3H]-H2O administration.
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PMID:Cyclohexanol and methylcyclohexanols. A family of inhibitors of hepatic HMGCoA reductase in vivo. 376 35

The cereal aleurone functions during germination by secreting hydrolases, mainly alpha-amylase, into the starchy endosperm. Multiple signal transduction pathways exist in cereal aleurone cells that enable them to modulate hydrolase production in response to both hormonal and environmental stimuli. Gibberellic acid (GA) promotes hydrolase production, whereas abscisic acid (ABA), hypoxia, and osmotic stress reduce amylase production. In an effort to identify the components of transduction pathways in aleurone cells, we have investigated the effect of okadaic acid (OA), a protein phosphatase inhibitor, on stimulus-response coupling for GA, ABA, and hypoxia. We found that OA (100 nM) completely inhibited all the GA responses that we measured, from rapid changes in cytosolic Ca2+ through changes in gene expression and accelerated cell death. OA (100 nM) partially inhibited ABA responses, as measured by changes in the level of PHAV1, a cDNA for an ABA-induced mRNA in barley. In contrast, OA had no effect on the response to hypoxia, as measured by changes in cytosolic Ca2+ and by changes in enzyme activity and RNA levels of alcohol dehydrogenase. Our data indicate that OA-sensitive protein phosphatases act early in the transduction pathway of GA but are not involved in the response to hypoxia. These data provide a basis for a model of multiple transduction pathways in which the level of cytosolic Ca2+ is a key point of convergence controlling changes in stimulus-response coupling.
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PMID:Okadaic acid, a protein phosphatase inhibitor, blocks calcium changes, gene expression, and cell death induced by gibberellin in wheat aleurone cells. 874 11

The mechanism of vesication from sulfur mustard remains unknown in spite of 80 years of investigation. We recently reported sulfur mustard-related inhibition of one or more protein (serine/threonine) phosphatases in tissue cytosol in vitro, suggesting a mechanism common to other vesicants such as cantharidin and Lewisite. Our investigation showed that this inhibition was related to the concentration of 2,2'-thiobis-ethanol (thiodiglycol), the hydrolysis product of sulfur mustard, rather than to the concentration of mustard itself. Related work showed an increase in the rate of NAD (but not NADP) reduction upon the addition of thiodiglycol to mouse liver cytosol. This result provided evidence that metabolism beyond thiodiglycol may be contributing to protein phosphatase inhibition. This observation indicated that metabolism involving one or more dehydrogenases may be necessary to produce the ultimate inhibitor of the protein phosphatases. We report here that thiodiglycol is a substrate for horse liver alcohol dehydrogenase (Km = 3.68+/-0.45 mM and Vmax = 0.22 +/-0.01 micromol min(-1) mg protein(-1)) and for pyridine nucleotide-linked enzymes in mouse liver and human skin cytosol. The alcohol dehydrogenase-specific inhibitor 4-methylpyrazole inhibited the oxidation of thiodiglycol by the pure horse liver enzyme as well as by the enzymes in human skin and mouse liver cytosol, indicating that the activity in the tissue preparations is also alcohol dehydrogenase.
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PMID:In vitro oxidation of the hydrolysis product of sulfur mustard, 2,2'-thiobis-ethanol, by mammalian alcohol dehydrogenase. 973 85

Symbiotic interactions between legumes and compatible strains of rhizobia result in root nodule formation. This new plant organ provides the unique physiological environment required for symbiotic nitrogen fixation by the bacterial endosymbiont and assimilation of this nitrogen by the plant partner. We have isolated two related genes (LjNPP2C1 and LjPP2C2) from the model legume Lotus japonicus that encode protein phosphatase type 2C (PP2C). Expression of the LjNPP2C1 gene was found to be enhanced specifically in L. japonicus nodules, whereas the LjPP2C2 gene was expressed at a similar level in nodules and roots. A glutathione S-transferase-LjNPP2C1 fusion protein was shown to have Mg2+- or Mn2+-dependent and okadaic acid-insensitive PP2C activity in vitro. A chimeric construct containing the full-length LjNPP2C1 cDNA, under the control of the Saccharomyces cerevisiae alcohol dehydrogenase promoter, was found to be able to complement a yeast PP2C-deficient mutant (pct1Delta). The transcript level of the LjNPP2C1 gene was found to increase significantly in mature nodules, and its highest expression level occurred after leghemoglobin (lb) gene induction, a molecular marker for late developmental events in nodule organogenesis. Expression of the LjNPP2C1 gene was found to be drastically altered in specific L. japonicus lines carrying monogenic-recessive mutations in symbiosis-related loci, suggesting that the product of the LjNPP2C1 gene may function at both early and late stages of nodule development.
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PMID:A protein phosphatase 2C gene, LjNPP2C1, from Lotus japonicus induced during root nodule development. 999 94

Cyclophilins are an evolutionarily conserved family of proteins which serve as the intracellular receptors for the immunosuppressive drug cyclosporin A. Here we report the characterization of the first cyclophilin cloned from the filamentous fungus Aspergillus nidulans (CYPB). Sequence analysis of the cypB gene predicts an encoded protein with highest homology to the murine cyclophilin B protein. The sequence similarity includes an N-terminal sequence predicted to target the protein to the endoplasmic reticulum (ER) as well as a C-terminal sequence predicted to retain the mature protein in the ER. The bacterially expressed hexa-histidine tagged protein displays peptidyl-prolyl isomerase activity which is inhibited by cyclosporin A. In the presence of cyclosporin A, the expressed protein also inhibits purified calcineurin. When the endogenous cypB gene was disrupted and placed under the control of the regulatable alcohol dehydrogenase promoter, the strain demonstrated no detectable growth phenotype under conditions which induce or repress cypB transcription. Induction or repression of the cypB gene also did not effect sensitivity of A. nidulans to cyclosporin A. cypB mRNA levels were significantly elevated under severe heat shock conditions, indicating a possible role for the A. nidulans cyclophilin B protein during growth in high stress environments.
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PMID:Molecular cloning and characterization of Aspergillus nidulans cyclophilin B. 1041 15

Ruminococcus albus 7 has played a key role in the development of the concept of interspecies hydrogen transfer. The rumen bacterium ferments glucose to 1.3 acetate, 0.7 ethanol, 2 CO2, and 2.6 H2 when growing in batch culture and to 2 acetate, 2 CO2, and 4 H2 when growing in continuous culture in syntrophic association with H2-consuming microorganisms that keep the H2 partial pressure low. The organism uses NAD(+) and ferredoxin for glucose oxidation to acetyl coenzyme A (acetyl-CoA) and CO2, NADH for the reduction of acetyl-CoA to ethanol, and NADH and reduced ferredoxin for the reduction of protons to H2. Of all the enzymes involved, only the enzyme catalyzing the formation of H2 from NADH remained unknown. Here, we report that R. albus 7 grown in batch culture on glucose contained, besides a ferredoxin-dependent [FeFe]-hydrogenase (HydA2), a ferredoxin- and NAD-dependent electron-bifurcating [FeFe]-hydrogenase (HydABC) that couples the endergonic formation of H2 from NADH to the exergonic formation of H2 from reduced ferredoxin. Interestingly, hydA2 is adjacent to the hydS gene, which is predicted to encode an [FeFe]-hydrogenase with a C-terminal PAS domain. We showed that hydS and hydA2 are part of a larger transcriptional unit also harboring putative genes for a bifunctional acetaldehyde/ethanol dehydrogenase (Aad), serine/threonine protein kinase, serine/threonine protein phosphatase, and a redox-sensing transcriptional repressor. Since HydA2 and Aad are required only when R. albus grows at high H2 partial pressures, HydS could be a H2-sensing [FeFe]-hydrogenase involved in the regulation of their biosynthesis.
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PMID:Hydrogen formation and its regulation in Ruminococcus albus: involvement of an electron-bifurcating [FeFe]-hydrogenase, of a non-electron-bifurcating [FeFe]-hydrogenase, and of a putative hydrogen-sensing [FeFe]-hydrogenase. 2515 86