Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00627 (MAP)
 15,705 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[alpha-32P]ATP was microinjected into Xenopus oocyte and neosynthesized cyclic AMP was isolated. Cholera toxin inhibited progesterone-induced maturation and stimulated after 3 h of preincubation the amount of neosynthesized cyclic AMP. Progesterone decreased the neosynthesis of cyclic AMP during the first hour following addition of the hormone.
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PMID:Cyclic AMP synthesis in Xenopus laevis oocytes: inhibition by progesterone. 8 80

The interrelationships among the processes of progesterone biosynthesis, respiration and energy production in human term placental mitochondria were examined. All substrates (citrate, isocitrate, alpha-ketoglutarate, succinate, fumarate, malate, glutamate, glycerol 3-phosphate, ascorbate + N,N,N',N'-tetramethyl-p-phenylenediamine) previously found to stimulate oxygen uptake and ATP synthesis in placental mitochondria supported progesterone synthesis from endogenous and exogenous cholesterol. Citrate support of progesterone synthesis was stimulated by NADP+ but not NAD+. It was inhibited by fluorocitrate and trans-aconitate but not by arsenite, rotenone, antimycin, cyanide or 2,4-dinitrophenol. Ascorbate-N,N,N',N'-tetramethyl-p-phenylenediamine support of progesterone synthesis was stimulated by NAD+ and NADP+ and was inhibited by ADP, rotenone, antimycin, cyanide and 2,4-dinitrophenol. Cyanide inhibition was relieved by an exogenous ATP regenerating system and ADP inhibition was reversed by oligomycin. Progesterone synthesis supported by alpha-ketoglutarate + malonate was stimulated by NAD+ and NADP+, and was completely inhibited by arsenite. 2,4-Dinitrophenol was strongly inhibitory both in the absence and presence of rotenon or antimycin. Stimulation by ATP was enhanced by rotenon, antimycin and oligomycin and inhibited by 2,4-dinitrophenol. Thus, metabolic control of progesterone synthesis by the energy status of the mitochondrial system was demonstrated when reducing equivalents were supplied via NADH or the respiratory electron transport chain.
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PMID:Mitochondria from human term placenta. III. The role of respiration and energy generation in progesterone biosynthesis. 92 26

Meiotic maturation of Xenopus laevis oocytes by progesterone requires translation of stored maternal mRNAs. We investigated the role of poly(A) tail elongation of mRNAs during this process using cordycepin, which inhibits poly(A) tail elongation of mRNAs. When oocytes were treated with the buffer containing 10 mM cordycepin for 12 h, concentration of 3'-dATP in cytosol of oocytes increased to 0.7 mM, while that of ATP remained constant at around 1.2 mM. Incorporation of [32P]AMP into poly(A) mRNA was inhibited almost completely by this treatment. Progesterone-induced germinal vesicle breakdown (GVBD) was also abolished. Dose dependence of inhibition of progesterone-induced GVBD on cordycepin was similar to that of [32P]AMP incorporation into poly(A) mRNA. However, maturation-promoting factor-induced GVBD was unaffected by treatment of oocytes with cordycepin. Furthermore, the inhibition of GVBD by cordycepin was rescued by removal of cordycepin even in the presence of actinomycin D. Therefore, we concluded that poly(A) tail elongation of mRNA is required for induction of meiotic maturation of X. laevis oocytes. In addition, progesterone induced a 2.7-fold activation of [32P]AMP incorporation into the poly(A) tail of mRNA after a lag period of 3 h whereas GVBD was induced after 6-8 h from the progesterone treatment. Syntheses of most of the proteins were unaffected by treatment of oocytes with progesterone or cordycepin. However, syntheses of several proteins were increased or decreased by progesterone and cordycepin treatment.
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PMID:Maturation of Xenopus laevis oocyte by progesterone requires poly(A) tail elongation of mRNA. 135 48

Although progesterone receptor status has been shown to correlate with response to hormonal therapy, not all progesterone receptor-positive patients respond to this treatment and additional biologic assays are needed to help better predict clinical response to hormonal therapy. This study explored the potential of the ATP bioluminescence assay and flow cytometry as biological assays of hormonal response. Five uterine cancer cell lines were used: AE7, ECC-1, HEC1A, AN3, and SKUT1B. Cells were exposed to Provera or tamoxifen at 0.1, 0.2, 0.5, 1, 2, and 5X (X equal to peak plasma concentrations: 1.0 micrograms/ml Provera and 0.1 micrograms/ml tamoxifen). For correlation, estrogen and progesterone receptors were determined by the standard dextran-coated charcoal method. Only AE7 and ECC-1 were positive for progesterone receptors (501 fmol/mg AE7, 194 fmol/mg ECC-1) and the rest were negative (less than 8 fmol/mg). Tamoxifen exerted no inhibition to the above cell lines. Meanwhile, Provera exerted dose-response inhibition on both AE7 and ECC-1 cell lines. The effects of accumulation of G0-G1 phase and reduction of S, G2 cells (P less than 0.05), but not on the HEC1A cell line (P = 0.4). These changes confirmed the antiproliferative property of Provera. Further studies are needed to establish the role of the ATP bioluminescence assay and flow cytometry as biological assays of hormonal response.
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PMID:Determination of hormonal response in uterine cancer cell lines by the ATP bioluminescence assay and flow cytometry. 138 55

The activating factor of ATP.Mg-dependent protein phosphatase (FA) has been identified in brain microtubules. When using purified MAP-2 (microtubule associated protein 2) and tau proteins as substrates, FA could phosphorylate MAP-2 to 16 moles of phosphates per mole of protein with a Km value of 0.4 microM, and tau proteins to 4 moles of phosphates per mole of proteins with a Km value of about 3 microM. When using microtubules as substrates, FA could enhance many-fold the endogenous phosphorylation of many microtubule-associated proteins including MAP-2, tau proteins, and several low-molecular-weight MAPs. In contrast to other reported MAP kinases, such as cAMP-dependent protein kinase and Ca+2/phospholipid-dependent protein kinase, the FA-catalyzed phosphorylation of tau proteins could cause an electrophoretic mobility shift on sodium dodecyl sulfate polyacrylamide gel electrophoresis, suggesting that a dramatic conformational change of tau proteins was produced by FA. Peptide mapping analysis of the phosphopeptides derived from SV8 protease digestion revealed that FA could phosphorylate MAP-2 and tau proteins on at least four specific sites distinctly different from those phosphorylated by cAMP-dependent and Ca+2/phospholipid-dependent MAP kinases. Quantitative analysis further indicated that approximately 19% of the total endogenous kinase activity in brain microtubules was due to FA. Taken together, the results provide initial evidence that the ATP.Mg-dependent protein phosphatase activating factor (FA) is a potent and unique MAP kinase, and may represent one of the major factors involved in phosphorylation of brain microtubules.
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PMID:Identification and characterization of the ATP.Mg-dependent protein phosphatase activator (FA) as a microtubule protein kinase in the brain. 165 23

A new high-resolution genetic linkage map for human chromosome 7p has been constructed. The map is composed of 47 loci (54 polymorphic systems), 19 of which are uniquely placed with odds of at least 1000:1. Four genes are represented, including glucokinase (GCK, ATP:D-hexose-6-phosphotransferase, EC 2.7.1.2) which was mapped via a (CA)n dinucleotide repeat polymorphism. The sex-average map measures 94.4 cM and the male and female maps measure 73.2 and 116.1 cM, respectively. We believe that the genetic map extends nearly the full length of the short arm of chromosome 7 since a centromere marker has been incorporated, and the most distal marker, D7S21, has been cytogenetically localized by in situ hybridization to 7p22-pter. The average marker spacing is 2 cM, and the largest interval between uniquely placed markers is 13 cM (sex-average map). Overall, female recombination was observed to be about 1.5 times that of males, and a statistically significant sex-specific recombination frequency was found for a single interval. The map is based on genotypic data gathered from 40 CEPH reference pedigrees and was constructed using the CRI-MAP program package. The map presented here represents a combined and substantially expanded dataset compared to previously published chromosome 7 maps, and it will serve as a "baseline" genetic map that should prove useful for future efforts to develop a 1-cM map and for construction of a contiguous clone-based physical map for this chromosome.
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PMID:A 2-cM genetic linkage map of human chromosome 7p that includes 47 loci. 174 Mar 42

Even though progestin is commonly added to many chemotherapy regimens in the treatment of uterine cancers, its role is still unproven. Since progestin is antiproliferative, its tendency to arrest cells in G1 phase may interfere with cytotoxic mechanisms. The ATP chemosensitivity assay and flow cytometry were used to study the effects of a progestational compound such as Provera on three single agents and four drug combinations. Uterine cancer cell lines included progesterone-receptor (PR)-positive AE7 and ECC1 and PR-negative HEC1A, HEC1B, AN3, and SKUT1B. Provera selectively affected only PR-positive cell lines. It imposed an antiproliferative effect on drug-induced cell-cycle perturbations by reducing G2 and S blocks and minimizing G1 depletion. When using IC50s (concentrations required for 50% growth inhibition) of 0.5 as a cutoff for drug sensitivity and resistance, Provera significantly improved the IC50s of the drug-resistant subgroup from 1.95 +/- 0.36 to 0.71 +/- 0.19 (P = 0.009) but not those of the drug-sensitive subgroup (P = 0.13). In summary, Provera appeared to work independently from cytotoxic mechanisms. Its improvement of cytotoxicity was most pronounced in resistant cell lines bearing progesterone receptors.
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PMID:The effects of Provera on chemotherapy of uterine cancer cell lines. 183 52

In closed-chest rats, isoproterenol (ISO, 25 mg/kg), 5 hours after subcutaneous administration, increased heart rate by 53%, left ventricular (LV) dP/dtmax by 80%, and cardiac output by 37%. LV systolic pressure (LVSP, -10%), mean arterial pressure (MAP, -12%), and total peripheral resistance (TPR, -36%) were diminished. In separate experiments, continuous intravenous infusion of adenine (50 mg/kg/hr) for 5 hours reduced heart rate (-11%), LVSP (-16%), MAP (-20%), TPR (-33%), and LV dP/dtmax (-20%). Cardiac output was increased (+20%). Inosine has been shown to have similar effects, except for a decline in cardiac output. Adenine (50 mg/kg/hr) attenuated the ISO-induced increase in heart rate and LV dP/dtmax and aggravated the decline in LVSP, MAP, and TPR. The increase in cardiac output was not changed. Inosine (200 mg/kg/hr) modified the ISO effects to a similar extent. Ribose (200 mg/kg/hr) added to the adenine infusion did not have functional effects. However, it aggravated the modifying influence of inosine on LVSP, LV dP/dtmax, and MAP. ISO reduced the cardiac ATP content (mumol/g) from a control value of 5.02 +/- 0.06 (n = 12) to 3.51 +/- 0.13 (n = 10). Adenine (3.56 +/- 0.21, n = 7) and ribose (3.64 +/- 0.11, n = 9) alone did not affect it, but inosine attenuated it (4.33 +/- 0.08, n = 8). Adenine and inosine in combination with ribose abolished the ISO-induced ATP decline (5.18 +/- 0.23, n = 7, and 4.76 +/- 0.10, n = 8, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nucleotide precursors modify the effects of isoproterenol. Studies on heart function and cardiac adenine nucleotide content in intact rats. 195 77

Previous studies with monoclonal antibodies indicate that sea urchin kinesin contains two heavy chains arranged in parallel such that their N-terminal ends fold into globular mechanochemical heads attached to a thin stalk ending in a bipartite tail [Scholey et al., 1989]. In the present, complementary study, we have used the monoclonal antikinesin, SUK4, to probe the quaternary structure of sea urchin (Strongylocentrotus purpuratus) kinesin. Kinesin prepared from sea urchin cytosol sedimented at 9.6 S on sucrose density gradients and consisted of 130-kd heavy chains plus an 84-kd/78 kd doublet (1 mol heavy chain: 1 mol doublet determined by gel densitometry). Low levels of 110-kd and 90-kd polypeptides were sometimes present as well. The 84-kd/78 kd polypeptides are thought to be light chains because they were precipitated from the kinesin preparation at a stoichiometry of one mol doublet per 1 mol heavy chain using SUK4-Sepharose immunoaffinity resins. The 110-kd and 90-kd peptides, by contrast, were removed using this immunoadsorption method. SUK4-Sepharose immunoaffinity chromatography was also used to purify the 130-kd heavy chain and 84-kd/78-kd doublet (1 mol heavy chain: 1 mol doublet) directly from sea urchin egg cytosolic extracts, and from a MAP (microtubule-associated protein) fraction eluted by ATP from microtubules prepared in the presence of AMPPNP but not from microtubules prepared in ATP. The finding that sea urchin kinesin contains equimolar quantities of heavy and light chains, together with the aforementioned data on kinesin morphology, suggests that native sea urchin kinesin is a tetramer assembled from two light chains and two heavy chains.
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PMID:Light chains of sea urchin kinesin identified by immunoadsorption. 214 20

The enhanced phosphorylations via cAMP, Ca2+ mobilization, and diacyl glycerol formation via the activation of the respective kinases is now classical. The decreased phosphorylation via inhibition of adenylate cyclase via the alpha adrenergic receptor is also becoming understood. What the insulin studies on the control of glycogen synthesis have taught us is that the rate limiting enzyme glycogen synthase is regulated by multiple covalent phosphorylation in an elegant but complex manner. The overall pattern of dephosphorylation is influenced by effecting both phosphatase and kinase activities in a set of interrelated mechanisms. In the presence of glucose, in muscle, fat, and liver under physiological conditions G-6-P acts as a signal to stimulate the phosphatase. An additional stimulation could occur via a novel insulin phosphatase stimulatory mediator. The phosphatase is also stimulated by at least three covalent mechanisms involving altered phosphorylation state. In one there is a decreased phosphorylation of the phosphatase inhibitor 1 potentially related to decreased cAMP-dependent protein kinase activity. In the second, there is decreased phosphorylation of the deinhibitor also potentially related to decreased cAMP-dependent protein kinase phosphorylation. In the third, an increased activity of casein kinase 2 could activate the ATP-Mg dependent phosphatase by an increased phosphorylation of phosphatase inhibitor 2 (modulatory subunit). In the liver, allosteric control of the phosphatase by G-6-P and nucleotides is of great importance. Insulin also stimulates the phosphatase in long-term experiments via increased protein synthesis. It is clear that future work will be required to determine which species of the various classes of phosphatases are regulated in short-term and long-term regulation by insulin. In terms of kinases, the effects of insulin to inactivate and desensitize the cAMP-dependent protein kinase are established. The molecular mechanisms of this effect remain to be worked out. The enhanced activity of MAP and S-6 kinase would appear to be part of a cascade of reactions perhaps originating in the autophosphorylation and activation of the insulin receptor tyrosine kinase. The mechanism of the short-term activation of casein kinase 2 remains to be elucidated. A cAMP-dependent protein kinase inhibitory mediator, which also inhibits adenylate cyclase is an important element in the regulation of kinase and adenylate cyclase activity by insulin. Its physiological significance must be established in the future, in terms of its control of glycogen synthase activation by insulin. Clearly this kinase inhibitor as well as the phosphatase stimulator are potential regulators of glycogen synthase activity by insulin.
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PMID:Insulin and the stimulation of glycogen synthesis. The road from glycogen structure to glycogen synthase to cyclic AMP-dependent protein kinase to insulin mediators. 215 10


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