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31.
Eberhard Fuchs Jan-Christian Wasmuth Gabriele Flügge Gerald Huether Raphael Troost Jürgen Beyer 《Cellular and molecular neurobiology》1996,16(1):21-37
Summary 1. Corticotropin-releasing factor (CRF) is thought to be involved in the regulation of the diurnal activity of the hypothalamus-pituitary-adrenal
(HPA) axis and to act as a neurotransmitter in the brain. To date it is unknown whether the binding sites of the central CRF
system are subject to diurnal variations.
2. We measured the number of CRF binding sites over the course of a complete 24-hr light-dark cycle in the pituitary, amygdala,
bed nucleus of the stria terminalis (BNST), cingulate cortex, visceral cortex, paraventricular nucleus of the hypothalamus,
hippocampus, and locus ceruleus of rats byin vitro receptor autoradiography with iodinated ovine CRF. A 24-hr time course was also established for plasma CRF and corticosterone.
3. The diurnal pattern of plasma CRF does not correlate with the pattern of plasma corticosterone. Within the brain, CRF binding
in the basolateral nucleus of the amygdala showed a U-shaped curve with maximum levels in the morning and a wide hallow between
1500 and 0100. A biphasic profile with a small depression in the afternoon and a more pronounced depression in the second
half of the activity period is characteristic for the other brain areas and the pituitary. The profile for the pituitary correlates
with those for the BNST and the area of the locus ceruleus. Furthermore, the diurnal pattern of CRF binding sites in the BNST
correlates with that of the hippocampus, and the daytime pattern of the visceral cortex is similar to that of both the hippocampus
and the BNST.
4. Since the CRF-binding profiles in the brain and the pituitary clearly differ from the profiles of both plasma CRF and corticosterone,
one may assume that the diurnal pattern of central CRF binding sites is not directly coupled to the activity of the HPA axis. 相似文献
32.
Gabriele Bierbaum Friedrich Götz Andreas Peschel Thomas Kupke Mart van de Kamp Hans-Georg Sahl 《Antonie van Leeuwenhoek》1996,69(2):119-127
Lantibiotics are antibiotic peptides that contain the rare thioether amino acids lanthionine and/or methyllanthionine. Epidermin, Pep5 and epilancin K7 are produced by Staphylococcus epidermidis whereas gallidermin (6L-epidermin) was isolated from the closely related species Staphylococcus gallinarum. The biosynthesis of all four lantibiotics proceeds from structural genes which code for prepeptides that are enzymatically modified to give the mature peptides. The genes involved in biosynthesis, processing, export etc. are found in gene clusters adjacent to the structural genes and code for transporters, immunity functions, regulatory proteins and the modification enzymes LanB, LanC and LanD, which catalyze the biosynthesis of the rare amino acids. LanB and LanC are responsible for the dehydration of the serine and threonine residues to give dehydroalanine and dehydrobutyrine and subsequent addition of cysteine SH-groups to the dehydro amino acids which results in the thioether rings. EpiD, the only LanD enzyme known so far, catalyzes the oxidative decarboxylation of the C-terminal cysteine of epidermin which gives the C-terminal S-aminovinylcysteine after addition of a dehydroalanine residue.Abbreviations Dha
2,3-didehydroalanine
- Dhb
2,3-didehydrobutyrine
- Lan
lanthionine
- Melan
methyllanthionine 相似文献
33.
Folkert Reck Ernst Meinjohanns Matthias Springer Roland Wilkens Johannes A. L. M. Van Dorst Hans Paulsen Gabriele Möller Inka Brockhausen Harry Schachter 《Glycoconjugate journal》1994,11(3):210-216
UDP-GlcNAc: Man1-6R (1-2)-N-acetylglucosaminyltransferase II (GlcNAc-T II; EC 2.4.1.143) is a key enzyme in the synthesis of complexN-glycans. We have tested a series of synthetic analogues of the substrate Man1-6(GlcNAc1-2Man1-3)Man-O-octyl as substrates and inhibitors for rat liver GlcNAc-T II. The enzyme attachesN-acetylglucosamine in 1-2 linkage to the 2-OH of the Man1-6 residue. The 2-deoxy analogue is a competitive inhibitor (K
i=0.13mm). The 2-O-methyl compound does not bind to the enzyme presumably due to steric hindrance. The 3-, 4- and 6-OH groups are not essential for binding or catalysis since the 3-, 4- and 6-deoxy and -O-methyl derivatives are all good substrates. Increasing the size of the substituent at the 3-position to pentyl and substituted pentyl groups causes competitive inhibition (K
i=1.0–2.5mm). We have taken advantage of this effect to synthesize two potentially irreversible GlcNAc-T II inhibitors containing a photolabile 3-O-(4,4-azo)pentyl group and a 3-O-(5-iodoacetamido)pentyl group respectively. The data indicate that none of the hydroxyls of the Man1-6 residue are essential for binding although the 2- and 3-OH face the catalytic site of the enzyme. The 4-OH group of the Man-O-octyl residue is not essential for binding or catalysis since the 4-deoxy derivative is a good substrate; the 4-O-methyl derivative does not bind. This contrasts with GlcNAc-T I which cannot bind to the 4-deoxy-Man- substrate analogue. The data are compatible with our previous observations that a bisectingN-acetylglucosamine at the 4-OH position prevents both GlcNAc-T I and GlcNAc-T II catalysis. However, in the case of GlcNAc-T II, the bisectingN-acetylglucosamine prevents binding due to steric hindrance rather than to removal of an essential OH group. The 3-OH of the Man1-3 is an essential group for GlcNAc-T II since the 3-deoxy derivative does not bind to the enzyme. The trisaccharide GlcNAc1-2Man1-3Man-O-octyl is a good inhibitor (K
i=0.9mm). The above data together with previous studies indicate that binding of the GlcNAc1-2Man1-3Man- arm of the branched substrate to the enzyme is essential for catalysis.
Abbreviations: GlcNAc-T I, UDP-GlcNAc:Man1-3R (1-2)-N-acetylglucosaminyltransferase I (EC 2.4.1.101); GlcNAc-T II, UDP-GlcNAc:Man1-6R (1-2)-N-acetylglucosaminyltransferase II (EC 2.4.1.143); MES, 2-(N-morpholino)ethane sulfonic acid monohydrate. 相似文献
34.
Hans-Jochen Schfer Gabriele Rathgeber Achim Schuhen Richard J. Berzborn 《FEBS letters》1994,340(3):265-268
UV irradiation of the ATPase (CF1) from spinach chloroplasts in the presence of 3'-arylazido-β-alanyl-8-azido ATP (8,3'-DiN3ATP) results in a nucleotide-dependent inactivation of the enzyme and in a nucleotide-dependent formation of -β cross-links. The results demonstrate an interfacial localization of the nucleotide binding sites on CF1. 相似文献
35.
Stefan Boehm Sigismund Huck Gabriele Koth Helmut Drobny Ernst Agneter Ernst A. Singer 《Journal of neurochemistry》1994,63(1):146-154
Abstract: This study explores the role of cyclic AMP in electrically evoked [3H]noradrenaline release and in the α2-adrenergic modulation of this release in chick sympathetic neurons. Along with an increase in stimulation-evoked tritium overflow, applications of forskolin enhanced the formation of intracellular cyclic AMP. Both effects of forskolin were potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. The forskolin-induced increase in overflow was abolished by the Rp-diastereomer of cyclic AMP-thioate, an antagonist at cyclic AMP-dependent protein kinases, and 1,9-dideoxy-forskolin, an inactive analogue at adenylyl cyclase, had no effect on the evoked overflow. A 24-h pretreatment with either cholera toxin or forskolin reduced the subsequent forskolin-induced accumulation of cyclic AMP and inhibited the stimulation-evoked release. Basal cyclic AMP production, however, remained unaltered after forskolin treatment and was enhanced after 24 h of cholera toxin exposure. The α2-adrenergic agonist bromoxidine did not affect the formation of cyclic AMP stimulated by forskolin but reduced electrically evoked release. However, effects of bromoxidine on 3H overflow were attenuated by forskolin as well as by 8-bromo-cyclic AMP. Effects of bromoxidine on [3H]noradrenaline release were paralleled by an inhibition of voltage-activated Ca2+ currents, primarily through a delayed time course of current activation. This effect was abolished when either forskolin or 8-bromo-cyclic AMP was included in the pipette solution. Both substances, however, failed to affect Ca2+ currents in the absence of bromoxidine. These results suggest that the signaling cascade of the α2-adrenergic inhibition of noradrenaline release involves voltage-activated Ca2+ channels but not cyclic AMP. Elevated levels of cyclic AMP, however, antagonize this α2-adrenergic reduction, apparently through a disinhibition of Ca2+ channels. 相似文献
36.
37.
Polyamine Metabolism in Experimental Brain Tumors of Rat 总被引:3,自引:0,他引:3
Ralf-Ingo Ernestus Gabriele Röhn Konstantin-Alexander Hossmann Wulf Paschen 《Journal of neurochemistry》1993,60(2):417-422
Abstract: Biosynthesis and accumulation of the polyamines putrescine, spermidine, and spermine are closely associated with cellular growth processes. We examined polyamine levels and the activity of their first rate-limiting enzyme, ornithine decarboxylase (ODC), in stereotactically induced experimental gliomas of the rat brain 1 and 2 weeks after implantation. Regional ODC activity and polyamine levels were determined in the tumor and in the ipsi- and contralateral striatum, white matter, and cerebral cortex. In the tumor, both ODC activity and polyamine levels markedly increased with progressive tumor growth, as compared to those in the white matter of the opposite hemisphere. In the peritumoral brain tissue, ODC activity did not change, but there was a marked increase of putrescine and, to a lesser degree, of spermidine and spermine almost throughout the whole ipsilateral hemisphere. ODC activity, therefore, seems to be a reliable marker of neoplastic growth in the brain, which may be of use for new clinical concepts of the diagnosis and therapy of brain tumors. The more diffuse distribution of polyamines, however, may be associated with the formation and spreading of edema, which would explain some of the biological effects of tumors on distant brain tissue. 相似文献
38.
The methyl chloride metabolism of the homoacetogenic, methyl chloride-utilizing strain MC was investigated with cell extracts and cell suspensions of the organism. Cell extracts were found to contain all enzyme activities required for the conversion of methyl chloride or of H2 plus CO2 to acetate. They catalyzed the dechlorination of methyl chloride with tetrahydrofolate as the methyl acceptor at a rate of 20 nmol/min × mg of cell protein. Also, the O-demethylation of vanillate with tetrahydrofolate could be measured at a rate of 40 nmol/min × mg. Different enzyme systems appeared to be responsible for the dehalogenation of CH3Cl and for the O-demethylation of methoxylated aromatic compounds, since cells grown with methoxylated aromatic compounds exhibited a significantly lower activity of CH3Cl conversion than methyl chloride grown cells and vice versa. In addition, ammonium thiocyanate (5 mM) completely inhibited CH3Cl dechlorination, whereas the consumption of vanillate was not affected significantly. The data were taken to indicate, that the methyl chloride dehalogenation is catalyzed by a specific, inducible enzyme present in strain MC, and that tetrahydrofolate rather than the corrinoid-protein involved in acetate formation is the primary acceptor of the methyl group in the dechlorination reaction. 相似文献
39.
A nonradioactive labelling and detection method for plant genomic DNA analysis is compared to the radioactive method. The radioisotopes are replaced by a nucleotide, digoxigenin-11-dUTP, and the signal detection is accomplished by the enzymatic reaction of alkaline phosphatase, conjugated to anti-digoxigenin antibodies, with the chemiluminescent substrate AMPPD (3-(2-spiroadamantane)-4-methoxy-4(3 phosphorytoxy) phenyl-1, 2-dioxetane). The sensitivity of the radioactive and nonradioactive methods are directly compared using identical Southern blots subjected to the radioactive and nonradioactive detection. The advantages of this nonradioactive method are discussed. 相似文献
40.
An enantioselective HPLC bioassay has been developed relying on extraction of (R)- and (S)-atenolol from alkalinized plasma or serum (pH > 12) into dichloromethane containing 5% (v/v) 1-butanol followed by an achiral derivatization of the drug with phosgene leading to (R)- and (S)-oxazolidine-2-one derivatives. Under these conditions there was quantitative conversion of the acetamido group to the corresponding nitrile. These stable derivatives were separated on a (R,R)-diaminocylohexane-dinitrobenzoyl chiral stationary phase [(R,R)-DACH-DNB] using dichloromethane/methanol 98/2 as mobile phase. Determination limits of 0.5 ng for (R)- and 0.6 ng for (S)-atenolol could be achieved using fluorimetric detection. The assay was applied to a human pharmacokinetic study which was performed in a randomized cross-over, double-blind fashion in 12 healthy volunteers, administering single oral doses of 100 mg (R,S)-, 50 mg (R)-, and 50 mg (S)-atenolol AUC0–24 and Cmax values of (R)-atenolol were slightly but significant higher than those of (S)-atenolol. The R/S ratios were 1.09 for AUC(R)/AUC(S) and 1.03 for Cmax (R)/Cmax(S) (P < 0.01) respectively after administration of the racemic drug. However, there were no differences between AUC, Cmax, and t½ values of each enantiomer, whether they were administered as single enantiometers or in the form of its racemic mixture. © 1993 Wiley-Liss, Inc. 相似文献