In addition, T4 abolished sensitivity to the lysosomotropic agent methylamine and the autophagy inhibitor 3-methyladenine, suggesting that T4 inhibits ...
NASA Website
The growth of tumor isografts in inbred mice is inhibited by intraperitoneal injections of syngeneic spleen incubated, in vitro, with ribonucleic acid extracted from guinea pigs immunized with the same mouse tumor. This inhibition is partially tumor-specific. Treatment with ribonuclease abolishes the response.
NASA Astrophysics Data System (ADS)
presynaptic maturation can be abolished by treatments that inter- fered with presynaptic BDNF and Cdc42 signaling or actin polymerization. Activation of Cdc42 by applying BDNF or bradykinin mimicked the effect, was abolished by inhibiting BDNF and Cdc42 signaling. Thus, rapid presynaptic maturation induced by neuronal
E-print Network
Carbacholine reduced, while baclofen and norepinephrine increased resting membrane potential in earthworm somatic muscle cells. In the presence of carbacholine, neither norepinephrine, nor baclofen hyperpolarized the membrane. Ouabain decreased resting potential and abolished the effects of carbacholine, norepinephrine, and baclofen on membrane potential. It was hypothesized ...
PubMed
A patient with long-standing symptoms of detrusor instability has been treated by electrical stimulation of the spinal cord. Stimulation abolished all symptoms and unequivocally inhibited episodes of instability.
PubMed Central
An in vitro DNA polymerase I system was used to study the effects of divalent metal ions on DNA replication/repair. The metals Ba/sup + +/, Ca/sup + +/, Cu/sup + +/, Co/sup + +/, Ni/sup + +/, Cd/sup + +/, Hg/sup + +/, Pb/sup + +/, and Zn/sup + +/ increasingly inhibited DNA polymerization in the order listed. BSA had a profound effect in the system, ...
Energy Citations Database
In anaesthetized cats 3-phenoxypropylguanidine caused a contracture of the nictitating membrane, a dilatation of the pupil and a fall followed by a rise in the arterial blood pressure. In spinal preparations of cats the initial fall in blood pressure was usually absent and the rise in blood pressure subsided to a steady level, which was about 10 mm Hg above the initial pressure. The pressor action ...
of tubuloglomerular feedback (TGF) (furosemide) abolished the L-NAME effect on the myogenic response. RVR responses during furosemide, assuming complete inhibition of TGF, suggest a third mechanism that contributes 10-NAME was given during inhibition of TGF by furosemide. After a control period, the albumin solution was diluted 1
The effects of cadmium, lead, and zinc on the ability of guinea pig macrophages to migrate and to interact with migration inhibitory factor (MIF) were studied by cell electrophoresis and the indirect migration inhibition assay. The metals significantly inhibited the motility of the cells and decreased or abolished the effect of MIF on ...
that displayed spontaneous spike activity. The inhibition was abolished by the A1 adenosine receptor antagonist-67156 (6-N,N-diethyl-D- , -dibromomethyleneATP)(50 M)andbytheectonucleotidaseinhibitorAOPCP[adenosine-5, which is converted to adenosine by ectoenzymes and subsequently activates neuronal adenosine receptors
Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit ...
Small-cell lung carcinoma (SCLC) is an aggressive, rapidly growing and metastasizing, and highly fatal neoplasm. We report that vasoactive intestinal peptide inhibits the proliferation of SCLC cells in culture and dramatically suppresses the growth of SCLC tumor-cell implants in athymic nude mice. In both cases, the inhibition was mediated apparently by a ...
Cyanide inhibited unesterified fatty acid synthesis but stimulated glyceride synthesis from (1-/sup 14/C) acetate when Spinacia oleracea chloroplasts were incubated in basal media. Both unesterified fatty acid and glyceride accumulation were inhibited when chloroplasts were incubated in a diacylglycerol mode. Stimulation of chloroplast fatty acid synthesis ...
The ?- and ?-adrenoceptor activities of the isolated rat uterus during the oestrous cycle were intluenced greatly by temperature changes. During dioestrus, lowering the bath temperature to 25�C from 40�C increased two-fold the inhibition produced by (-)-adrenaline, (-)-noradrenaline, (-)-phenylephrine and (-)-isoprenaline. During oestrus adrenaline, noradrenaline and ...
The balance of excitation and inhibition converging upon a neurone is a principal determinant of neuronal output. We investigated the role of inhibition in shaping and gating inspiratory drive to hypoglossal (XII) motoneuronal activity. In neonatal rat medullary slices that generate a spontaneous respiratory rhythm, patch-clamp recordings were made from ...
ROMK1 channels are located in the apical membrane of the connecting tubule and cortical collecting duct and mediate the potassium secretion during normal dietary intake. We used a perforated whole-cell patch clamp to explore the effect of angiotensin II on these channels in HEK293 cells transfected with green fluorescent protein (GFP)-ROMK1. Angiotensin II inhibited ROMK1 ...
Scratching relieves itch, but the underlying neural mechanisms are poorly understood. We presently investigated a role for the inhibitory neurotransmitters GABA and glycine in scratch-evoked inhibition of spinal itch-signaling neurons in a mouse model of chronic dry skin itch. Superficial dorsal horn neurons ipsilateral to hindpaw dry skin treatment exhibited a high level of ...
In whole cells of Rhodopseudomonas sphaeroides, nitrogen fixation, as measured by hydrogen production and acetylene reduction, was totally inhibited by micromolar concentrations of ammonia. This inhibition could not be duplicated by glutamate or glutamine alone. The inhibition by ammonia was abolished by methionine ...
The male hormone androgen is a growth/survival factor for its target tissues or organs. Yet, the underlying mechanism is incompletely understood. Here, we report that androgen via p21 inhibits tumor necrosis factor ?-induced JNK activation and apoptosis. Inhibition by androgen requires the transcription activity of androgen receptor (AR) and de novo ...
Cyclic variations in coronary blood flow (CFVs) in dogs with experimental coronary artery stenosis and endothelial injury appear to result primarily from the aggregation of platelets at the site of stenosis followed by dislodgement and distal embolization. Using this canine model, we tested the hypotheses: (a) that thrombin is an important mediator of CFVs in dogs with coronary stenoses and ...
BackgroundThe GDNF family ligands (GFLs) are regulators of neurogenic inflammation and pain. We have previously shown that GFLs increase the release of the sensory neuron neuropeptide, calcitonin gene-related peptide (CGRP) from isolated mouse DRG.ResultsInhibitors of the mitogen-activated protein kinase (MAPK) pathway abolished the enhancement of CGRP release by GDNF. ...
Intracellular recordings were made from isolated bundles of the circular muscle layer of guinea-pig gastric antrum and the responses evoked by stimulating nitrergic nerve fibres were examined. Nitrergic inhibitory junction potentials (nitrergic-IJPs), evoked by trains of stimuli, had small amplitudes and were associated with a reduction in the rate of occurrence and amplitude of spontaneously ...
Transforming growth factor (TGF)-?1 has been reported to cause endothelial cell apoptosis. However, conflicting data have also demonstrated that TGF-?1 promotes endothelial cell survival. In this study, the effect of TGF-?1 on apoptosis of cultured bovine pulmonary artery endothelial cells (PAEC) induced by multiple stimuli was investigated. TGF-?1 protected against apoptosis of bovine PAEC ...
Title: The estrogen effects on endothelial repair and mitogen-activated protein kinase activation-nitro-L-arginine methyl ester (L-NAME) Short title: Endothelial NO synthase and estradiol effects Audrey Billon hyperplasia in rats3 and medial hyperplasia in mice4 . In addition, E2 promotes vasorelaxation and inhibits
Regulatory decrease in thymocyte volume under conditions of osmotic stress was abolished by potassium and chlorine channel blockers. Osmotic stress-activated chlorine channels belong to 2 pharmacological types. The maxi-anion channel is sensitive to Gd(3+). The volume-sensitive outwardly rectifying chlorine channel is inhibited with glybenclamide and ...
. Fluorescence res- onance energy transfer (FRET) from the CFP to the YFP indicated interaction between-depen- dent FRET to YFP-tagged nuclear receptor interaction domains of the coactivators SRC-1 and PBP. The ER that was abolished by the receptor antago- nists tamoxifen or ICI182,780. Inhibition of FRET by tamoxifen but not ICI
DNA polymerases delta and ..cap alpha.. were purified from CV-1 cells, and their sensitivities to the inhibitors aphidicolin, (p-n-butylphenyl) deoxyguanosine triphosphate (BuPdGTP), and monoclonal antibodies directed against DNA polymerase ..cap alpha.. were determined. The effects of these inhibitors on DNA replication, measured with (/sup 3/H)TTP, in permeabilized CV-1 cells were studied to ...
In the present study, we characterized OXSI-2 ([3-(1-Methyl-1H�indol �3-yl-methylene)-2�oxo-2, 3�dihydro-1H- indole�5-sulfonamide], a putative inhibitor of Syk, and determined its specificity and selectivity in platelets. We found that OXSI-2 completely abolished convulxin-induced platelet functional responses. In order to determine whether OXSI-2 ...
Zinc ions, at concentrations which were shown to inhibit guanylate cyclase activity, abolished the actions of prolactin on RNA and casein synthesis in cultured mouse mammary gland explants. These observations are compatible with the hypothesis that certain of the actions of prolactin in the mammary gland may be mediated by cyclic GMP.
The room temperature fluorescence induction of chloroplasts was utilized as a probe to locate the site of inhibition on PSII by copper. It was found that, while the initial fluorescence yield was hardly affected, the variable fluorescence yield was lowered without significant change in its kinetics. Addition of DCMU, or abolishing oxygen evolution ...
The aim of this study was to evaluate the effects of lactoferrin (LF) on the growth of fibroblasts derived from nasal polyps. We showed that the proliferation of fibroblasts was inhibited in a dose-dependent manner by both native and recombinant LF. The greatest inhibition of proliferation was caused by human milk-derived, iron-saturated LF. The ...
The molecular mechanisms responsible for the �distal� effect by which noradrenaline (NA) blocks exocytosis in the ?-cell were examined by whole-cell and cell-attached patch clamp capacitance measurements in INS 832/13 ?-cells. NA inhibited Ca2+-evoked exocytosis by reducing the number of exocytotic events, without modifying vesicle size. Fusion pore ...
NMDA receptors are of particular importance in the control of synaptic strength and integration of synaptic activity. Dopamine receptor modulation of NMDA receptors in neonatal striatum may influence the efficacy of synaptic transmission in the cortico-striatal pathway and if so, this modulation will affect the behaviour of the basal ganglia network. Here, we show that in acute brain slices of ...
Neostigmine (2.2 ?g/ml.) or physostigmine (3.3 ?g/ml.) contracted guinea-pig isolated tracheal chains. The anticholinesterase diisopropylphosphodiamidic fluoride (mipafox) itself caused no contractile response even in concentrations of 100 ?g/ml., yet neostigmine or physostigmine still caused contractions after treatment with mipafox. The responses were abolished by hyoscine ...
Bacterial pathogens have evolved a sophisticated arsenal of virulence factors to modulate host cell biology. Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC) use a type III protein secretion system (T3SS) to inject microbial proteins into host cells. The T3SS effector cycle inhibiting factor (Cif) produced by EPEC and EHEC is able to block host ...
Flavonoid-containing plant preparations (water soluble extracts of Pentaphylloides fruticosa [Extralife], Emblica officinalis Gaerth [Amla], and Bergenia crassifolia [Bergenia]) produced a dose-dependent and tissue-specific effect on activity of mitochondrial ATP-dependent potassium channel. The effect of these preparations was biphasic (activation and inhibition). The ...
3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone), an effective free radical scavenger, provides neuroprotection in stroke models and patients. In this study, we investigated its neuroprotective effects in a chronic rotenone rat model for Parkinson's disease. Here we showed that a five-week treatment with edaravone abolished rotenone's activity to induce catalepsy, damage ...
The aims of the present study were to determine whether prostaglandins (PGs) and PPAR? are involved in the stimulation of tissue-non-specific alkaline phosphatase (TNAP) activity and mineralization by TNF-? in human osteoblasts. We used osteoblasts differentiated from MSCs from three different donors and MG-63 osteoblast-like cells. Inhibition of prostaglandin synthesis with ...
In the present study, we investigated the effects of calmodulin, adenosine 5{prime}-triphosphate (ATP) and pertussis toxin (PT) on phorbol ester (PMA) induced inhibition of ANF-stimulated cyclic GMP formation in cells from the human renal cell line, SK-NEP-1. PMA inhibited ANF-stimulated guanylate cyclase activity in particulate membranes by about 65%. ...
Myosin light chain kinase (MLCK) phosphorylates the light chain of smooth muscle myosin enabling its interaction with actin. This interaction initiates smooth muscle contraction. MLCK has another role that is not attributable to its phosphorylating activity, i.e., it inhibits the ATP-dependent movement of actin filaments on a glass surface coated with phosphorylated myosin. To ...
In early vertebrate development, mesoderm induction is a crucial event regulated by several factors including the activin, BMP and FGF signaling pathways. While the requirement of FGF in Nodal/activin-induced mesoderm formation has been reported, the fate of the tissue modulated by these signals is not fully understood. Here, we examined the fate of tissues when exogenous activin was added and FGF ...
Uranyl nitrate abolishes the uptake of oxygen associated with glucose utilization by conidia of Neurospora sitophila approximate ED/sub 50/ is 1.0 f UO/sub 2/ g per 10/sup 5/ spores. Endogenous oxygen uptake is not, however, affected by the presence of uranium the respiratory quotient with glucose drops to the endogenous level. Phosphate reverses the uranium ...
Equinatoxin is a lethal protein isolated from a sea anemone, Actinia equina. The toxin (0.1-3 micrograms/ml) caused an initial inhibition followed by an augmentation of contractions and beating rates in the isolated guinea-pig atrium. The inhibitory phase was transient (30-60 sec), while the stimulant phase lasted for about 30 min. The treated atrium showed tachyphylaxis to ...
The amount of soybean agglutinin (SBA) detectable by radioimmunoassay in seeds of resistant cultivars to Phytophthora megasperma var. sojae was approximately twice that of susceptible cultivars. SBA was preferentially released at earlier times (6-9 hours) and in higher amounts in the imbibate from resistant cultivars as compared to susceptible cultivars. The lectin in the imbibate was ...
Hormone replacement therapy (HRT) for post-menopausal symptoms in diabetes is associated with increased risk of coronary heart disease and stroke. Therefore, there is a need for new HRT with no adverse effects on diabetic post-menopausal women. We developed peptides as potential estrogen mimetic compounds and now we evaluated the effects of the most efficacious peptide; hexapeptide ...
The authors analysed the capacity of various temperature fractions of RNA isolated from the spleen of donors of the bone marrow cells (of mice C57BL/6I) and recipients--hybrids (CBA X C57BL/6I) F1 to abolish the depression of colony formation in the nonsyngenous organism. In the administration of bone marrow cells of mice of parental genotype C57BL/6I of the irradiated ...
The effects of several membrane antibiotics and other agents on ATP-dependent protein translocation were examined in membrane vesicles under conditions where no significant proton motive force was present. The membrane perturbants ethanol and procaine abolished ATP-dependent protein translocation. Phenethyl alcohol at low concentrations abolished ...
We recently reported that dexamethasone (DEX) enhances acetylcholine (ACh) release from pituitary cell aggregates. In the present study, the effect of DEX on the GH-releasing properties of the cholinergic agonist carbachol (CCh) was investigated. Perifusion of hemipituitaries from 14-day-old rats with CCh stimulated basal GH release. CCh also increased basal GH release from organ-cultured ...
1. Stimulation of cardiac sympathetic nerves caused prolonged inhibition of vagal effects on heart rate, an effect which has been proposed on the basis of previous studies to be due to neuropeptide Y or a neuropeptide Y-like substance, released from the sympathetic nerves. 2. This prolonged vagal inhibitory effect was attenuated or abolished when the ...
For a compound to inhibit potently the transformation of amorphous calcium phosphate into hydroxyapatite, it is suggested that the minimum structural requirement is a phosphate group and, at some other position, either another phosphate group preferably or a carboxylic moiety. Primary amino groups abolish inhibitor potential. Inhibitor potency is modified ...
Ciliated ependymal cells line the ventricular surfaces and aqueducts of the brain. In ex vivo experiments, pneumolysin caused rapid inhibition of the ependymal ciliary beat frequency and caused ependymal cell disruption. Wild-type pneumococci and pneumococci deficient in pneumolysin caused ciliary slowing, but penicillin lysis of wild-type, not pneumolysin-deficient, ...
Neuronal rhythmic activities within thalamocortical circuits range from partially synchronous oscillations during normal sleep to hypersynchrony associated with absence epilepsy. It has been proposed that recurrent inhibition within the thalamic reticular nucleus serves to reduce synchrony and thus prevents seizures. Inhibition and synchrony in slices from ...
The HRPT2 (hereditary hyperparathyroidism type 2) tumor suppressor gene encodes a ubiquitously expressed 531 amino acid protein termed parafibromin. Inactivation of parafibromin predisposes one to the development of HPT-JT syndrome. To date, the role of parafibromin in tumorigenesis is largely unknown. Here, we report that parafibromin is a nuclear protein that possesses anti-proliferative ...
Inhibitory activity directed against metalloenzymes has been highly purified from extracts of red kidney beans (Phaseolus vulgaris). The inhibitor is a substance of small molecular weight and appears to be a chelator of Zn2+. One milligram of the preparation inhibited 23 milligrams carboxypeptidase A. The inhibitor also strongly ...
The authors have examined the effects of anti-inflammatory and anti-rheumatic drugs on membrane-bound and purified Na /K -ATPase activity in vitro. Only the gold-containing compounds (gold sodium thiomalate and auranofin) were found to inhibit the enzyme activity in a dose-dependent manner. Sodium thiomalate and triethylphosphine, the ligand compounds for gold sodium ...
We tested the hypothesis that nitric oxide (NO) and vasodilating prostaglandins (PGs) contribute independently to hypoxic vasodilatation, and that combined inhibition would reveal a synergistic role for these two pathways in the regulation of peripheral vascular tone. In 20 healthy adults, we measured forearm blood flow (Doppler ultrasound) and calculated forearm vascular ...
Veratridine produced a dose-dependent release of cytoplasmic [3H]dopamine in rat corpus striatal slices. Cytoplasmic [3H]dopamine was obtained by pretreating rats with reserpine to inhibit vesicular storage and incubating with pargyline and beta-thujaplicin to inhibit catabolism prior to incubation with [3H]dopamine. Release of [3H]dopamine by veratridine ...
The function of Lhca4, a gene encoding the photosystem 1 type IV chlorophyll a/b-binding protein complex in Arabidopsis, was investigated using antisense technology. Lhca4 protein was reduced in a number of mutant lines and abolished in one. The inhibition of protein was not correlated with the inhibition of mRNA. No depletion of Lhca1 ...
Both polyunsaturated fatty acids and AMPK promote energy partitioning away from energy consuming processes, such as fatty acid synthesis, towards energy generating processes, such as ?-oxidation. In this report, we demonstrate that arachidonic acid activates AMPK in primary rat hepatocytes, and that this effect is p38 MAPK-dependent. Activation of AMPK mimics the inhibition by ...
The state-3 rate of respiration of potato tuber mitochondria is inhibited by concentrations of KCl or NaCl above 125 mM, and by concentrations of sucrose, lactose, or maltose above 500 mM, but not at all by mannitol, glucose, glycine, or proline up to a concentration of 1500 mM in the medium. Mitochondria from cauliflower, beetroot, cucumber, rock melon, and watermelon behave ...
Myosin Va is a well known processive motor involved in transport of organelles. A tail-inhibition model is generally accepted for the regulation of myosin Va: inhibited myosin Va is in a folded conformation such that the tail domain interacts with and inhibits myosin Va motor activity. Recent studies indicate that it is the C-terminal ...
1. Five mM glycodeoxycholate and glycochenodeoxycholate inhibit net fluid transport across isolated rat jejunum and ileum; 5 mM glycocholate does not affect jejunal segments, but arrests fluid transport across ileal segments. 2. Inhibition of fluid transport is accompanied by some diminution of mucosal glucose uptake, but translocation of glucose to the ...
Phosphoribosyl pyrophosphate (PRPP) synthetase purified from rat liver loses activity when assayed at low protein concentrations, which results in a nonlinear relationship between velocity and enzyme concentration. A linear relationship is obtained at higher enzyme concentrations or in the presence of albumin, EDTA, or sulfhydryl compounds. Iodoacetamide and p-chloromercuribenzoate ...
5-Aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), an analog of AMP, is widely used as an activator of AMP-kinase (AMPK), a protein that regulates the responses of the cell to energy change. We studied the effects of AICAR on the growth of retinoblastoma cell lines (Y79, WERI, and RB143). AICAR inhibited Rb cell growth, induced apoptosis and S-phase cell cycle ...
Stress induced by application of electric foot shocks (300 microA/shock, five shocks per episode, 4 episodes at 1800, 1830, 1900 and 1930 hrs on the proestrus day) to rats at the time of pre-ovulatory progesterone secretion, abolished lordosis and resulted in maximum rejection co-efficient, whereas treatment with a CRF receptor antagonist (alpha-helical CRF9-41) or metapirone, ...
Both epinephrine and manganese are known to stimulate cAMP production in cardiac homogenates. When added together, however, they inhibited adenylyl cyclase catalytic activity. Type V adenylyl cyclase, the major isoform in the heart, was also inhibited when an increasing concentration of epinephrine was added in the presence of manganese. ...
The effect of cadmium and zinc ions on violaxanthin cycle enzymes, violaxanthin de-epoxidase and zeaxanthin epoxidase, has been investigated on selected plant species, as well as in vitro. About 50% inhibition of zeaxanthin epoxidase by cadmium ions was found for duckweed (Lemna trisulca) and tomato (Lycopersicon esculentum) leaves but for apricot (Prunus armeniaca) leaves no ...
1 Ions of the lanthanide series (lanthanum-lutetium) inhibit histamine release induced by allergen and anti-IgE in the presence of extracellular calcium. The inhibition is dose-dependent in the range 10(-6) to 10(-9) M and there is no marked difference in potency between the lanthanides. 2 The response to lanthanum is biphasic and higher concentrations ...
A chemical genetics approach was taken to identify inhibitors of NS1, a major influenza A virus virulence factor that inhibits host gene expression. A high-throughput screen of 200,000 synthetic compounds identified small molecules that reversed NS1-mediated inhibition of host gene expression. A counterscreen for suppression of influenza virus cytotoxicity ...
This study evaluated the response of the Na(+)/H(+) exchanger (NHE) to dopamine D(1)- and D(2)-like receptor stimulation in immortalized renal proximal tubular epithelial cells and freshly isolated renal proximal tubules from the spontaneously hypertensive rat (SHR) and their normotensive controls (Wistar Kyoto rats; WKY). Stimulation of D(1)-like receptors with SKF 38393 attenuated NHE activity ...
1. The content of adenosine triphosphate (ATP) and basal and bradykinin-stimulated production of prostacyclin and endothelium-derived relaxing factor (EDRF) was measured in primary cultures of porcine aortic endothelial cells under normoxic (14.4% O2) and hypoxic (2.8% O2) conditions, and following treatment with rotenone and 2-deoxy glucose, which inhibit oxidative and ...
1. Inhibition by haloperidol and chlorpromazine of a voltage-activated K+ current was characterized in rat phaeochromocytoma PC12 cells by use of whole-cell voltage-clamp techniques. 2. Haloperidol or chlorpromazine (1 and 10 microM) inhibited a K+ current activated by a test potential of +20 mV applied from a holding potential of -60 mV. The K+ current ...
Transforming growth factor (TGF)-beta1 has been reported to cause endothelial cell apoptosis. However, conflicting data have also demonstrated that TGF-beta1 promotes endothelial cell survival. In this study, the effect of TGF-beta1 on apoptosis of cultured bovine pulmonary artery endothelial cells (PAEC) induced by multiple stimuli was investigated. TGF-beta1 protected against apoptosis of bovine ...
The basolateral 50-pS K channels are stimulated by a cAMP-dependent pathway and inhibited by cytochrome P-450-omega-hydroxylase-dependent metabolism of arachidonic acid (AA) in the rat thick ascending limb (TAL). We now used the patch-clamp technique to examine whether stimulation of adenosine A(?a) receptor modulates the inhibitory effect of AA on the basolateral 50-pS K ...
Two compartments have been defined in monoaminergic synaptic vesicles: the core or central compartment, storage site for monoamines, and the matrix or outer compartment, of unknown function. The outer compartment reacts with the mixture of zinc iodide-osmium tetroxide (ZIO). This reaction is temperature and time dependent and may be abolished by -SH reagents. The effect of ...
The present study was undertaken to investigate the cardiovascular effect of three extracts from the root bark of Anthocleista schweinfurthii Gilg.: an aqueous extract (AE), a dichloromethane extract (DCMR) and a fraction enriched in cardiac glycoside type compounds (CARDAN). In isolated perfused frog heart, bolus injection of the extracts produced a positive inotropic effect. The responses to AE ...
Recent studies suggest that TJ-41, a herbal drug, possesses chemotherapeutic effects. Accordingly, this study was undertaken to investigate the anticarcinogenic effects of TJ-41 on human breast cancer cells lines. TJ-41 inhibited the proliferation of human breast cancer cell lines dose dependently. Flow cytometric analysis showed that this decrease in DNA synthesis is to be ...
Intact cells of several strains of Pseudomonas aeruginosa agglutinate papain-treated human erythrocytes. The agglutinating activity appears to reside in the surface layers of the bacterium-Pseudomonas surface haemagglutinin. This activity does not correlate with the existence of the internal PA-I and PA-II lectins, the presence of fimbriae or adherence to human buccal epithelial cells. Disruption ...
N-Methyl-D-aspartate (NMDA) receptors appear to be involved in CS processing and memory consolidation. The present paper analyzed the effect of the non-competitive NMDA receptor antagonist Dizocilpine maleate (MK-801) on Latent Inhibition (LI)-retarded learning of a CS-US association after to-be-CS preexposures at time of testing, using Wistar rats as experimental subjects. If ...
Oxidative stress of human skin fibroblasts by treatment with ultraviolet A (UVA) radiation has been shown to lead to an increase in levels of the heme catabolizing enzyme heme oxygenase 1 [heme, hydrogen-donor:oxygen oxidoreductase (?-methene-oxidizing, hydroxylating), EC 1.14.99.3] and the iron storage protein ferritin. Here we show that human skin fibroblasts, preirradiated with UVA, sustain ...
Estrogen is frequently prescribed as a method of birth control and as hormone replacement therapy for post-menopausal women with varied effects on cognition. Here the effects of estrogen on attention were examined using the latent inhibition (LI) behavioral paradigm. Ovariectomized (OVX) female rats were given either estrogen benzoate (EB, 10 or 100[mu]g/ml/kg; SC) or sesame ...
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Male gametogenesis occurs directly after uptake of malaria parasites by the mosquito vector and leads to the release of eight nucleated flagellar gametes. Here, we report that one of the two parasite actin isoforms, named actin II, is essential for this process. Disruption of actin II in Plasmodium berghei resulted in viable asexual blood stages, but male gametogenesis was specifically ...
1. A study has been made in the anaesthetized cat of the stimulation parameters required to separate the vasodilator and vasoconstrictor responses evoked in the nose by stimulating the cut peripheral end of the Vidian nerve. 2. The extent of the vasodilation and vasoconstriction was found to be dependent on the stimulation frequency, but whereas vasodilation reached a maximum at 25 Hz, ...
dependence on NMDA receptor (NMDAR) activation, BDNF signaling, and NO synthesis. Finally, we demonstrated/ LTD at retinotectal synapses by inhibiting BDNF/NO sig- naling selectively abolished the asymmetric of brain-derived neurotrophic factor (BDNF) to the tectum (Du and Poo, 2004). To examine the role of BDNF
Active and passive sensitization, both in vivo and in vitro, caused significant hyperpolarization of airway smooth muscle cell preparations isolated from guinea pigs. An increase in the contribution of the electrogenic Na+ pump to the resting membrane potential was responsible for this change. Hyperpolarization, as induced by passive sensitization, was not prevented by agents that ...
This study evaluated the transduction pathway associated with type 3 Na(+)/H(+) exchanger (NHE3) activity-induced inhibition during dopamine D(3) receptor activation in immortalized renal proximal tubular epithelial cells from the spontaneously hypertensive rat. The dopamine D(3) receptor agonist 7-OH-DPAT decreased NHE3 activity, which was prevented by the D(2)-like receptor ...
The synthesis of vaccinia virus-induced thymidine kinase is normally arrested several hours after infection. In thymidine kinase-deficient LM cells infected with IHD strain of vaccinia virus, arrest occurs whether or not viral DNA synthesis is inhibited. With virus inactivated by uv irradiation, enzyme synthesis takes place, but arrest is ...
In the present study, we examined the inhibitory effects of protein tyrosine phosphatase (PTPase) inhibitors, including sodium orthovanadate (SOV), ammonium molybdate (AM), and iodoacetamide (IA), on cell growth, accumulation of astaxanthin, and PTPase activity in the photosynthetic algae Haematococcus lacustris. PTPase activity was assayed spectrophotometrically and was found to be ...
Venom extract of Conus striatus elicited a rhythmic, transient contraction of the guinea-pig isolated ileum followed by a relaxation at concentrations greater than 1 microgram/ml, which was abolished by tetrodotoxin and a low-Na medium. The contraction induced by the venom was inhibited by atropine but not mecamylamine, whereas the relaxation was not ...
Growth of Meth-A tumor in CDF1 mice was inhibited significantly by injection of a hot water extract of a strain of Chlorella vulgaris (CE) into the tumor or into the subcutaneous tissue near the tumor. The augmentation of resistance by CE may require the participation of T cells and macrophages, since it was abolished or reduced in athymic nude mice or ...
During maximal exercise, supraspinal fatigue contributes significantly to the decline in muscle performance but little is known about intracortical inhibition during such contractions. Long-interval inhibition is produced by a conditioning motor cortical stimulus delivered via transcranial magnetic stimulation (TMS) 50�200 ms prior to a second test ...
1. The transport of HCO3- (Jsm) from a HCO3(-)-buffered serosal to an unbuffered mucosal saline solution has been studied in rat caecum in vitro. 2. Carbachol, bethanechol and acetylcholine (ACh) caused a concentration-dependent fall in Jsm with similar maximum effects. 1,1-Dimethyl-4-phenyl-piperazinium iodide (DMPP) also inhibited Jsm but the effect was less than with the ...
1. The possible involvement of a spinal site of sympatho-inhibitory action in the baroreceptor reflex pathways was investigated by determining the effect of phenylephrine-induced, baroreceptor-mediated inhibition on a spinally evoked excitatory response of renal nerve activity before, during and after removal of tonic descending excitatory drive from the rostral ventrolateral ...
Although inflammatory pathways have been linked with various chronic diseases including cancer, identification of an agent that can suppress these pathways has therapeutic potential. Herein we describe the identification of a novel compound bharangin, a diterpenoid quinonemethide that can suppress pro-inflammatory pathways specifically. We found that bharangin suppresses NF-?B activation induced ...
During entrance into torpor heart and respiration rates are greatly reduced in parallel with the reduction of metabolic rate, suggesting an involvement of parasympathetic control. We compared the effect of parasympathetic inhibition with the effect of sympathetic inhibition on spontaneous torpor behaviour in the Djungarian hamster. Hamsters were acclimated ...
The antibiotic granaticin interferes in Bacillus subtilis with the charging process of tRNALeu causing both the arrest of protein synthesis and bacteriostasis [A. Ogilvie, K. Wiebauer & W. Kersten (1975) Biochem. J. 152, 511-515]. A concomitant inhibition of RNA synthesis is observed. This inhibition was studied with mutant strains of B. subtilis. 2. ...
The plant signals strigolactones activate seed germination of the parasitic weeds (Striga and Orobanche), growth of arbuscular mycorrhizal (AM) fungi and have recently been described as a new class of plant hormones that inhibit shoot branching. In AM fungi, the synthetic strigolactone analogue GR24 rapidly stimulates mitochondrial metabolism (within minutes) and biogenesis ...
Modafinil is a well-tolerated medication for excessive sleepiness, attention-deficit disorder, cocaine dependence and as an adjunct to antidepressants with low propensity for abuse. We investigated the modafinil action on identified dopaminergic and GABAergic neurons in the ventral tegmental area (VTA) and substantia nigra (SN) of rat brain slices. Modafinil (20 microM) ...
Adenoviral expression of human APP (hAPP), but not of hAPP deleted from its C-terminal intracellular domain, in rat cortical neurons abolishes spontaneous synchronous calcium oscillations. The intracellular domain of APP695 contains several residues that can be phosphorylated. Contrary to non-neuronal cells, a very high phosphorylation of APP on T668 is observed in neurons, ...
The effect of cadmium on hepatic drug metabolizing enzymes and the involvement of metallothionein in the protection of the impaired activity of these enzymes was studied. Administration of cadmium (cadmium chloride) to mice significantly inhibited the activity of aminopyrine N-demethylation in 24 and 48 hr, but the activity returned to nearly control values in 72 hr. The ...
The present magnetoencephalography (MEG) study on auditory evoked magnetic fields (AEFs) was aimed at verifying whether during dichotic listening the contralateral auditory pathway inhibits the ipsilateral one, as suggested by behavioural and patient studies. Ten healthy subjects were given a randomized series of three complex tones (261, 293 and 391 Hz, 500 ms duration), ...
In asynchronous RTG-2 cell cultures infected with infectious pancreatic necrosis (IPN) virus, inhibition of cellular DNA synthesis, but not protein synthesis, was detected 5 to 6 h postinfection and was 80 to 90% complete by 7 to 8 h. Inhibition of DNA synthesis was largely abolished by UV irradiation of the virus. Sedimentation ...
The human epidermoid carcinoma cell line A431 becomes highly sensitive to Shiga toxin upon treatment with butyric acid. This strong sensitization (> 1000-fold) is accompanied by an increase in the fraction of cell-associated toxin transported to the Golgi apparatus and to the endoplasmic reticulum (ER). Furthermore, our previous work showed that the length of the fatty acyl chain of Gb3, the ...
H(2) is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis, may promote endothelial dysfunction by binding the cell-surface receptor LOX-1. LOX-1 expression can be upregulated by various stimuli, including TNF-?. Thus, we aimed to examine whether the upregulation of LOX-1 by different stimuli could be blocked by H(2) ...
The effects of cimetidine, ranitidine, histamine and histidine, as well as of their copper complexes, have been examined in an enzymic and chemical O2- generated systems. Copper complexes like CuZnSOD inhibited both the reduction of cytochrome c and NBT2+ in xanthine-xanthine oxidase systems, but their inhibitory action was due to a certain extent to the copper-induced ...
We previously observed that gangliosides GM2, GM1, and GM3 inhibit Ca2+-uptake via the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) in neurons and in brain microsomes. We now systematically examine the effect of various gangliosides and their analogs on Ca2+-uptake via SERCA and demonstrate that an exposed carboxyl group on the ganglioside sialic acid residue is required ...
We have developed a screening system for artificial small RNAs (sRNAs) that inhibit the growth of Escherichia coli. In this system, we used a plasmid library to express artificial sRNAs (approximately 200 bases long) containing 60 bases of random nucleotide sequence. The induced expression of the known rydB sRNA in the system reduced the amount of its possible target mRNA, ...
1. The effects of i.v. administration of the glycine-antagonist strychnine nitrate and the GABA-antagonists bicuculline hydrochloride and picrotoxin on the recurrent inhibition of lumbosacral alpha-motoneurones were studied in cats anaesthetized with pentobarbitone sodium. 2. As revealed from both monosynaptic reflex experiments and intracellular recordings, each of the drugs ...
The effects of blue light and calcium on elongation of hypocotyl segments of Cucumber (Cucumis sativa L. cv Burpee's Pickler) were studied. Cucumber seedlings grown in dim red light showed a rapid decline in the rate of hypocotyl elongation when irradiated with high intensity (100 micromoles per square meter per second) blue light. In intact, 4-day-old seedlings the inhibition ...
Rationale: Inhibition of glycogen synthase kinase-3 (GSK-3) protects the heart during ischemia/reperfusion (I/R), yet the underlying mechanisms of cardioprotection afforded by beta isoform-specific inhibition GSK-3 remain to be elucidated. Objective: We studied the molecular mechanism mediating the effect of GSK-3? ...
Endothelial cell-dependent vascular relaxation plays an important role in the regulation of blood pressure. Here, we show that stimulation of vascular endothelial cells with platelet-derived growth factor (PDGF) results in vascular relaxation through Akt1-dependent activation of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production. Stimulation of both human umbilical artery ...
In smooth muscle of the guinea-pig bladder, either membrane potential recordings or [Ca2+]i measurements were made simultaneously with isometric tension recordings.Single transmural stimuli initiated excitatory junction potentials (EJPs) which triggered action potentials, transient increases in [Ca2+]i and ...
Repeated association of drugs of abuse with context leads to long-lasting behavioral responses that reflect reward-controlled learning and participate in the establishment of addiction. Reactivation of consolidated memories is known to produce a reconsolidation process during which memories undergo a labile state. We investigated whether reexposure to drugs had similar effects. Cocaine ...
1. To clarify the cause of uncoupling of Ca influx through Ca channels and the contractility of the myocardium in hibernating chipmunks, the electromechanical effects of two different internal Ca store inhibitors, caffeine and ryanodine, and a cardiotonic agent, isoprenaline, were investigated in papillary muscles of hibernating animals. 2. Ryanodine (10(-6) M), an inhibitor of internal Ca ...
Cardiovascular responses to intravenous administration of a piperamide analogue, LASSBio 365, were investigated in anesthetized rats. LASSBio 365 [62.5-1000 microg/kg, intravenously (IV)] has potent cardiovascular effects that include hypotension and bradycardia, accompanied by a brief pressor effect and apnea. Bilateral vagotomy or atropine injection (2 mg/kg, IV) completely ...
We describe a method to design dominant-negative proteins (D-N) to the basic helix�loop�helix�leucine zipper (B-HLHZip) family of sequence-specific DNA binding transcription factors. The D-Ns specifically heterodimerize with the B-HLHZip dimerization domain of the transcription factors and abolish DNA binding in an equimolar competition. Thermal denaturation studies ...
Cobrotoxin (CbT), a short-chain postsynaptic ?-neurotoxin, has been reported to play a role in analgesia. However, to date, the detailed mechanisms still remain unknown. In the present study, we identify a novel functional role of CbT in modulating T-type Ca(2+) channel currents (T-currents) in small dorsal root ganglia (DRG) neurons as well as pain behaviors in mice. We found that CbT ...
NADPH-dependent superoxide production by intact human neutrophils is inhibited by DPI (diphenyleneiodonium), when stimulated by either FMLP (N-formylmethionyl-leucyl-phenylalanine) or PMA (phorbol 12-myristate 13-acetate). Addition of 10 microM-DPI abolished the reduction of both the FAD and the cytochrome b components of the NADPH oxidase. DPI ...
Experiments of outbred rats with modeled xenobiotic load with acetylsalicylic acid (250 mg/kg for 7 days) revealed inhibition of mitochondrial respiration rate in states of rest and active phosphorylation, inhibition of succinate-dependent oxidation pathway, and a decrease in energization of organelles in the heart. For correction of the observed changes ...
The effects of mepyramine, promethazine, chlorpromazine and lysergic acid diethylamide have been compared on the capillary permeability changes of the skin, produced by histamine, by 5-hydroxytryptamine and by passive cutaneous anaphylaxis in mice. Promethazine, mepyramine and chlorpromazine can inhibit, in decreasing order of activity, the effect of histamine, whilst lysergic ...
Oxygen electrode and fluorescence studies demonstrate that linear electron transport in the freshwater alga Chlamydomonas reinhardtii can be completely abolished by abrupt hyperosmotic shock. We show that the most likely primary site of inhibition of electron transfer by hyperosmotic shock is a blockage of electron transfer between plastocyanin (PC) or ...
Monoclonal antibodies of IgG2a isotype specifically inhibited growth of human tumors in nude mice. Twentythree monoclonal antibodies of other isotypes showed no tumoricidal reactivity. Complement depletion of nude mice had no effect on tumor suppression by monoclonal antibody. The role of T and killer cells as mediators of the monoclonal antibody effect in nude mice was ...
The neuropeptide galanin is widely distributed throughout the central and peripheral nervous systems of mammalian, avian, reptilian, and fish species and has a broad range of physiological and behavioral effects. Human galanin is a 30-amino-acid non-C-terminally amidated peptide that potently stimulates growth hormone secretion, inhibits cardiac vagal slowing of heart rate, ...
... system for interagency coordination, effectively abolishing the lessons ... unity of effort of the interagency response. ... Commander should be abolished. ...
DTIC Science & Technology
Transplanted neural stem and progenitor cells (NSCs) produce mostly astrocytes in injured spinal cords. Lithium stimulates neurogenesis by inhibiting GSK3b (glycogen synthetase kinase 3-beta) and increasing WNT/beta catenin. Lithium suppresses astrogliogenesis but the mechanisms were unclear. We cultured NSCs from subventricular zone of neonatal rats and showed that lithium ...
The alpha-glucosidase inhibitors N-methyl-1-deoxynojirimycin (MDNJ) and castanospermine have been shown to inhibit angiogenesis. A hybrid of 1-deoxynojirimycin (DNJ) and an aryl-1,2,3-triazole, which inhibits both an alpha-glucosidase and methionine aminopeptidase-2 (MetAP2), displayed properties associated with inhibition of ...
1. Membrane potential recordings were made from longitudinal smooth muscle cells of the guinea-pig urethra using conventional microelectrode techniques. 2. Smooth muscle cells of the urethra developed spontaneous transient depolarizations (STDs) and slow waves. Single unit STDs had amplitudes of approximately 5 mV and slow waves seemed to occur as amplitude multiples of single unit STDs. 3. STDs ...
Membrane potential recordings were made from longitudinal smooth muscle cells of the guinea-pig urethra using conventional microelectrode techniques.Smooth muscle cells of the urethra developed spontaneous transient depolarizations (STDs) and slow waves. Single unit STDs had amplitudes of approximately 5 mV and slow waves seemed to occur as amplitude multiples of single unit STDs.STDs and slow ...
Excitatory motor innervation to the internal anal sphincter (IAS) of the monkey, the rabbit and mouse were compared. Contractile responses to electrical field stimulation of nerves (EFS, atropine 1 micromol L(-1) and N(omega)-nitro-L-arginine 100 micromol L(-1) present throughout) were examined in isolated strips of IAS. In the monkey IAS, EFS caused frequency dependent (1-30 Hz) contractions ...
Intracellular electrical activity was recorded from smooth muscle tissues of the mouse proximal colon, and the impaled cells were visualized by injection of neurobiotin. Slow potentials with initial fast and subsequent plateau components (plateau potentials), generated at a frequency of 14.8 min?1, were recorded from oval-shaped cells with bipolar processes. Periodic bursts ...
The present experiment was designed to examine possible influence of adrenergic nerves on nicotine-induced neurogenic vasodilation in porcine basilar arteries denuded of endothelium. Nicotine and transmural nerve stimulation (TNS) induced relaxation of basilar arteries. Tetrodotoxin (TTX) abolished the relaxation elicited by TNS, but only partially blocked that induced by ...
We test the hypothesis that 12-hydroperoxyeicosatetraenoic acid (12(s)-HPETE) and 12-hydroxyeicosatetraenoic acid (12-HETE) perfused into the renal pelvis increase afferent renal nerve activity (ARNA) and suppress renin release in rats fed a low-salt (LS) diet via activation of the transient receptor potential vanilloid type 1 (TRPV1) expressed in renal sensory nerves. 12(s)-HPETE or 12-HETE given ...
1. Changes in membrane potential of the guinea-pig isolated taenia caeci evoked by single stimuli have been investigated using intracellular recording techniques. Nifedipine (10 microM) was used to arrest spontaneous muscle action potentials. Single stimuli elicited complex junction potentials which consisted of both excitatory and inhibitory components. 2. The excitatory component of the compound ...
Teleost retinal cones elongate in the dark and contract in the light. In isolated retinas of the green sunfish Lepomis cyanellus, cone myoids undergo microtubule-dependent elongation from 5 to 45 micron. We have previously shown that cone contraction can be reactivated in motile models of cones lysed with Brij-58. Reactivated contraction is both actin and ATP dependent, activated by calcium, and ...
VEGF-, phosphoinositide 3-kinase (PI3K)- and protein kinase C (PKC)-regulated signaling in cardiac and vascular differentiation was investigated in mouse ES cells and in ES cell-derived Flk-1? cardiovascular progenitor cells. Inhibition of PI3K by wortmannin and LY294002, disruption of PI3K catalytic subunits p110? and p110? using short hairpin RNA (shRNA), or ...
We previously reported that testosterone attenuated atherogenesis in LDLR?/? male mice, and that this effect of testosterone was most likely caused by its conversion to estradiol. Estradiol inhibits vascular cell adhesion molecule-1 (VCAM-1) expression, and expression of VCAM-1 is one of the early events in atherogenesis. We assessed the cellular ...
Xanthohumol (XN), a prenylated chalcone isolated from hop plant, exhibits anti-inflammatory, antiproliferative, and antiangiogenic properties through an undefined mechanism. Whether examined by intracellular esterase activity, phosphatidylserine externalization, DNA strand breaks, or caspase activation, we found that XN potentiated tumor necrosis factor�induced apoptosis in leukemia and myeloma ...
Granzyme-mediated cell death is the major pathway for cytotoxic lymphocytes to kill virus-infected and tumor cells. In humans, five different granzymes (i.e. GrA, GrB, GrH, GrK, and GrM) are known that all induce cell death. Expression of intracellular serine protease inhibitors (serpins) is one of the mechanisms by which tumor cells evade cytotoxic lymphocyte-mediated killing. Intracellular ...
Arachidonic acid (AA) regulates intracellular calcium concentration ([Ca2+]i) in a variety of cell types including salivary cells. In the present study, the effects of serine/threonine phosphatases on AA-induced Ca(2+) signaling in mouse parotid acini were determined. Mice were euthanized with CO2. Treatment of acini with the serine/threonine phosphatase inhibitor calyculin A blocked both ...
In the rat hepatic artery, the endothelium-derived hyperpolarizing factor (EDHF) was identified as potassium. Potassium hyperpolarizes the smooth muscles by gating inward rectified potassium channels and by activating the sodium-potassium adenosine triphosphatase (Na(+)-K(+)ATPase). Our goal was to examine whether potassium could explain the EDHF in porcine coronary arteries. On coronary strips, ...
In the rat hepatic artery, the endothelium-derived hyperpolarizing factor (EDHF) was identified as potassium. Potassium hyperpolarizes the smooth muscles by gating inward rectified potassium channels and by activating the sodium-potassium adenosine triphosphatase (Na+-K+ATPase). Our goal was to examine whether potassium could explain the EDHF in ...
Interleukin-1 (IL-1) is a major proinflammatory cytokine produced by monocytes/macrophages. At the inflammatory site, IL-1 is a potent inducer of the production of prostaglandin E2 (PGE2) and metalloproteinases on fibroblast-like cells, thus triggering tissue damage. The biological activity of IL-1 is counterbalanced by two types of inhibitors: the IL-1 receptor antagonist (IL-1Ra) which ...
In experiments on unanaesthetized rabbits, myoelectric activity (contractile activity index) of distal ileum, caecum, and proximal colon in two sites was studied under stress induced by fastening a rabbit to the table in supine position. The stress caused sharp decrease (up to complete disappearance) of the contractile activity in all studied compartments of the ileocaecal intestine with partial ...
Myosin VIIA is an unconventional myosin, responsible for human Usher syndrome type 1B, which causes hearing and visual loss. Here, we studied the molecular mechanism of regulation of myosin VIIA, which is currently unknown. Although it was originally thought that myosin VIIA is a dimeric myosin, our electron microscopic (EM) observations revealed that full-length Drosophila myosin VIIA (DM7A) is a ...
1. Cholera enterotoxin was used to evaluate a possible role of endogenous cyclic AMP in production of hyperthermia. Injection of purified toxin (0�10-1�0 ?g in 0�10 ml.) into the lateral cerebral ventricle of unanaesthetized cats caused dose-related hyperthermic responses. Heating the toxin for 40 min at 90� C abolished its hyperthermic activity. 2. Intraventricular ...
During the reaction catalyzed by the phosphofructokinase (EC 2.7.1.11) from Escherichia coli, the phosphoryl group transferred from ATP interacts with Thr-125 [Shirakihara, Y. & Evans, P. R. (1988) J. Mol. Biol. 204, 973-994]. The replacement of Thr-125 by serine changes the saturation by fructose 6-phosphate from cooperative to hyperbolic and abolishes the allosteric ...
Mps1 is an essential component of the spindle assembly checkpoint. In this study, we describe a novel Mps1 inhibitor, AZ3146, and use it to probe the role of Mps1�s catalytic activity during mitosis. When Mps1 is inhibited before mitotic entry, subsequent recruitment of Mad1 and Mad2 to kinetochores is abolished. However, if Mps1 is ...
It has long been known that certain antibiotics, at subinhibitory concentrations, differentially inhibit the synthesis of ?-hemolysin and other staphylococcal virulence factors. In this report, we show that subinhibitory clindamycin (SBCL) eliminates production of nearly all exoproteins by Staphylococcus aureus but has virtually no effect on cytoplasmic proteins. The effect ...
Somatostatin has been shown to inhibit antral motility in vivo. To examine the effect of somatostatin on cholinergic neurotransmission in the canine antrum, we studied the mechanical response of and the release of ({sup 3}H)acetylcholine from canine longitudinal antral muscle in response to substance P, gastrin 17, and electrical stimulation. In unstimulated tissues, ...
Rat CINC induced a dose- and time-dependent accumulation of neurophils into murine air-pouches, a response which was inhibited by two selective H1-antagonists, mepyramine and triprolidine (approximately 60%). As pretreatment with fucoidin abolished CINC effect, the relative time-related contribution of selectins on this process was then investigated by ...
Pyrrolidine dithiocarbamate (PDTC) suppresses NF-kappaB activity and exhibits cytotoxic effects in bovine cerebral endothelial cells (BCECs), and we have previously reported that these PDTC effects were accompanied by an increase in intracellular zinc levels. To further explore the role of zinc in the modulation of NF-kappaB activation, we studied the effect of pyrithione, a zinc ionophore, on ...
It was reported that glucocorticoid production was inhibited by fenofibrate through suppression of type-1 11{beta}-hydroxysteroid dehydrogenase gene expression in liver. The inhibition might be a negative-feedback regulation of glucocorticoid receptor (GR) activity by peroxisome proliferator-activated receptor alpha (PPAR{alpha}), which is quickly induced ...
Dilations produced with UK-14304, a selective alpha 2-adrenoceptor agonist, in rat middle cerebral arteries (MCAs) were blocked after removal of the endothelium or inhibition of nitric oxide synthase (NOS). After endothelium removal or inhibition of NOS, the addition of subthreshold doses of an exogenous nitric oxide (NO) donor, ...
An enzyme hitherto named semicarbazide-sensitive amine oxidase (SSAO), involved in the oxidation of primary amines, is abundantly expressed in adipocytes. Although SSAO physiological functions remain unclear, several molecules inhibiting its activity have been described to limit fat accumulation in preadipocyte cultures or to reduce body weight gain in obese rodents. Here, we ...
Abstract The objective of this study was to investigate whether nanoparticle-exposure affects enzyme function and to determine the mechanisms responsible. Silicon, Au, and CdSe nanoparticles were synthesized in house and their physicochemical properties were characterized. The activity of purified lactate dehydrogenase (LDH) was inhibited or abolished by ...
D-serine is a physiologic coagonist with glutamate at NMDA-subtype glutamate receptors. As D-serine is localized in glia, synaptically released glutamate presumably stimulates the glia to form and release D-serine, enabling glutamate/D-serine cotransmission. We show that serine racemase (SR), which generates D-serine from L-serine, is physiologically inhibited by ...
3-(3'-isocyanocyclopent-2-enylidene) propionic acid at a concentration of 2 to 5 ..mu..g ml/sup -1/ inhibited cellulose digestion by a mixed culture of rumen microorganisms and in other experiments inhibited the degradation of timothy had (Phleum pratense) in a digestibility test. At isocyanide concentrations of 12 ..mu..g ml/sup -1/ the ...
3-(3?-Isocyanocyclopent-2-enylidene)propionic acid at a concentration of 2 to 5 ?g ml?1 inhibited cellulose digestion by a mixed culture of rumen microorganisms and in other experiments inhibited the degradation of timothy hay (Phleum pratense) in a digestibility test. At isocyanide concentrations of 12 ?g ml?1 ...
Whole-cell voltage-clamp recordings from dissociated hair cells of the statocyst of octopus, Eledone cirrhosa, demonstrated that application of ACh, carbachol or muscarine (10 microM) reversibly decreased the amplitude of L-type calcium current (I(Ca,L)), while nicotine (10-100 microM) did not have any effect. Furthermore, atropine blocked the effect of ACh and agonists suggesting that ACh reduces ...
We have previously shown that the biphenylcarboxylic acid butanediol ester (ABD56) inhibits osteoclast formation and activity in vitro and in vivo. However, the mechanism of action of this compound is unknown. ABD56 inhibited osteoclast formation and caused osteoclast apoptosis, but had no effects on osteoblasts or macrophages. As the NF{kappa}B and MAPK ...
Matrine and oxymatrine, major components of Sophora flavescens, were confirmed to have a protective effect on restraint and water immersion stress ulcer in mice. Oxymatrine inhibits the formation of some experimental gastric ulcer, pylorus ligation ulcer and indomethacin ulcer, which are considered to relate to acid secretion. Oxymatrine decreases acid secretion in Shay's rats ...
Matrix metalloproteinase (MMP) plays a crucial role in periodontal disease and is up-regulated by oral Gram-negative, pathogen-derived LPS. In this study, we reported that simvastatin, a 3-hydroxyl-3-methylglutaryl-CoA reductase inhibitor, effectively inhibited LPS-stimulated MMP-1 as well as MMP-8 and MMP-9 expression by U937 mononuclear cells. Our studies showed that the ...
Certain synthetic peptides derived from the Fc region of human IgG suppressed protein, RNA, and DNA synthesis during mixed lymphocyte reactions. Responder mononuclear cells were incubated with medium or agents that alter phosphorylation of cellular proteins before immunomodulatory Fc peptides and stimulator cells were added. Incubating cells with trifluoperazine which inhibits ...
The effect of guanine nucleotides on purified Guinea pig liver transglutaminase (Gpig TG) activity was investigated. Guanosine 5'-triphosphate (GTP) at concentrations 20-200 ..mu..M inhibited purified TG. GTP specifically inhibited Gpig TG, since platelet Factor XIIIa (platelet TG) was not inhibited by GTP. Kinetic studies ...
Inhibition studies of amino acids in Nicotiana silvestris suspension cells gave clues to the difficulties for obtaining mutants deficient in post prephenate pathway proteins of aromatic amino acid biosynthesis (prephenate aminotransferase, arogenate dehydrogenase and arogenate dehydratase). Such mutants, if successfully obtained, would allow gene-enzyme relationships of ...
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Aluminium (Al) is phytotoxic when solubilized into Al(3+) in acidic soils. One of the earliest and distinct symptoms of Al(3+) toxicity is inhibition of root elongation. To decipher the mechanism by which Al(3+) inhibits root elongation, the role of ethylene and auxin in Al(3+)-induced inhibition of root elongation in Arabidopsis ...
A major subtype of glutamate receptors, AMPA receptors (AMPARs), are generally thought to mediate excitation at mammalian central synapses via the ionotropic action of ligand-gated channel opening. It has recently emerged, however, that synaptic activation of AMPARs by glutamate released from the climbing fibre input elicits not only postsynaptic excitation but also presynaptic ...
The aim of the present study was to examine the effect of an early stage of streptozotocin-induced diabetes on the mechanism(s) of endothelium-dependent relaxation. Diabetes was induced by a single injection of streptozotocin (48 mg/kg iv), and the ACh-induced relaxation of rat carotid arteries was examined 6 wk later. A diabetes-induced increase in superoxide levels, determined by L-012-induced ...
1 The effect of the Ca(2+)-ATPase inhibitor, cyclopiazonic acid (CPA), was studied on rat thoracic aortic ring preparations. 2 At concentrations above 0.3 microM, CPA induced relaxation in the arteries precontracted with phenylephrine. Removal of the endothelium abolished CPA-induced relaxation. 3 The nitric oxide (NO) synthase inhibitor NG-nitro L-arginine (3-300 microM), the ...
The phosphorylation profile of ciliary proteins under basal conditions and after stimulation by extracellular ATP was investigated in intact tissue and in isolated cilia from porcine airway epithelium using anti-phosphoserine and anti-phosphothreonine specific antibodies. In intact tissue, several polypeptides were serine phosphorylated in the absence of any treatment (control conditions). After ...
In endothelial cells, the AMP-activated protein kinase (AMPK) is stimulated by sheer stress or growth factors that stimulate release of nitric oxide (NO). We hypothesized that NO might act as an endogenous activator of AMPK in endothelial cells. Exposure of human umbilical vein endothelial cells (HUVECs) to NO donors caused an increase in phosphorylation of both Thr-172 of AMPK and Ser-1177 ...
The 13-lined ground squirrel (Ictidomys tridecemlineatus), a hibernating species, is a natural model of physiological adoption to an extreme environment. During torpor, body temperature drops to 0-4 degrees C, and the cortex is electrically silent, yet the brain stem continues to regulate cardiorespiratory function. The mechanisms underlying selective inhibition in the brain ...
The 13-lined ground squirrel (Ictidomys tridecemlineatus), a hibernating species, is a natural model of physiological adaption to an extreme environment. During torpor, body temperature drops to 0�4�C, and the cortex is electrically silent, yet the brain stem continues to regulate cardiorespiratory function. The mechanisms underlying selective inhibition in the brain ...
The effects of galanin (7-70 nM) on ATP-sensitive K+ channels (KATP channels), membrane potential and the release of insulin have been studied in the insulinoma cell line, RINm5F. Single-channel currents have been recorded from excised outside-out membrane patches as well as intact insulin-secreting cells and it is shown that galanin, added to the outside of the membrane, specifically activates ...
As chronic stress and depression have become recognized as significant risk factors for peripheral vascular disease in patients with no prior history of vasculopathy, we interrogated this relationship utilizing an established mouse model of chronic stress/depressive symptoms from behavioral research. Male mice were exposed to 8 wk of unpredictable chronic mild stress (UCMS; e.g., wet bedding, ...
Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), which is produced primarily by macrophages and is predominately found in the blood and in atherosclerotic plaques, represents a potentially promising target for combating atherosclerosis. Although statins are known to decrease the levels and activity of circulating and plaque Lp-PLA(2) during atherosclerosis, little is known regarding the ...
The role of sphingosine 1-phosphate (S1P)-induced Rho kinase (ROCK) activation in the angiogenic responses of pulmonary artery-derived endothelial cells (PAEC) and smooth muscle cells (PASMC) was examined. S1P, a biologically active phospholipid that regulates angiogenesis, promoted PAEC chemotaxis and capillary morphogenesis; furthermore, this activity was unaltered by pretreatment with the ...
The nucleus of the solitary tract (NTS) receives inputs from both arterial chemoreceptors and central noradrenergic neural structures activated during hypoxia. We investigated NE modulation of chemoreceptor afferent integration following a chronic exposure to sustained hypoxia (CSH; 7-8 days at 10% FIO2). Whole-cell recordings of NTS second-order neurons identified by DiA ...
The basolateral amygdala (BLA) has a fundamental role in affective processing. In vivo studies have revealed rhythmic population activity of a similar type to that seen in the hippocampus and cortical areas during learning tasks. The amygdala contains densely interconnected networks of inhibitory interneurons similar to those responsible for fast network activity generation in the hippocampus and ...
1. The actions of BaCl2 and 4-aminopyridine, blockers of K+ channels, on the mechanical activity of the epididymal half of the rat vas deferens were investigated. 2. Both BaCl2 and 4-aminopyridine dose-dependently evoked phasic contractions. High extracellular potassium (35-40 mM) caused a tonic contraction but abolished the BaCl2- and 4-aminopyridine-induced phasic activity ...
The relationship between stimulus-induced repetitive antidromic firing (ADF) in the motor nerve and twitch potentiation produced by the organophosphate anticholinesterase paraoxon, has been investigated in rat diaphragm preparations. Little or no ADF was produced by paraoxon in preparations bathed in a Tyrode solution containing 1 mM calcium and 1 mM magnesium ions although the preparations showed ...
Conductance-based models of reciprocally inhibiting burst neurons suggest that intrinsic membrane properties and postinhibitory rebound (PIR) determine the amplitude and frequency of saccadic oscillations. Reduction of the low-threshold calcium currents (I(T) ) in the model decreased the amplitude but increased the frequency of the simulated oscillations. Combined reduction of ...
The circular muscle strip is a new preparation for examining the action of drugs on the circular muscle of the guinea-pig isolated intestine. The preparation differed from the longitudinal muscle in that it was insensitive to drugs which act on autonomic effector tissues but, after inhibition of cholinesterase, it responded readily to choline esters, 5-hydroxytryptamine, ...
The beneficial effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) beyond cholesterol lowering involve their direct actions on vascular smooth muscle cells (VSMCs). However, the effects of statins on phenotypic modulation of VSMCs are unknown. We herein show that simvastatin (Sm) and atorvastatin (At) inhibited DNA synthesis in human aortic VSMCs ...
In eukaryotic cells, the nuclear envelope partitions the nucleus from the cytoplasm. The fission yeast Schizosaccharomyces pombe undergoes closed mitosis in which the nuclear envelope persists rather than being broken down, as in higher eukaryotic cells. It is therefore assumed that nucleocytoplasmic transport continues during the cell cycle. Here we show that nuclear transport is, in fact, ...
Macropinocytosis is a type of poorly characterized fluid-phase endocytosis which results in formation of relatively large vesicles. We report that Sonic hedgehog (Shh) protein induces macropinocytosis in the axons, through activation of a noncanonical signaling pathway including Rho GTPase and nonmuscle myosin II. Macropinocytosis induced by Shh is independent of clathrin-mediated endocytosis, but ...
The porphycenes represent a new class of photosensitizing agent with enhanced absorbance in the red. We examined the photodynamic effects of two porphycenes, a monomer and a pyrazine-linked dimer, using the P388 murine leukemia and P388/ADR, a subline that expresses the multidrug-resistance phenotype. The monomer localized at mitochondrial loci while the dimer photosensitized lysosomes and the ...
Vascular endothelial growth factor (VEGF) binding to the kinase domain receptor (KDR/FLK1 or VEGFR�2) mediates vascularization and tumor-induced angiogenesis. Since there is evidence that KDR plays an important role in tumor angiogenesis, we sought to identify peptides able to block the VEGF�KDR interaction. A phage epitope library was screened by affinity for membrane-expressed KDR or for an ...
1. Administration of lithium to rats causes a rise in plasma glucose and suppresses glucose-stimulated insulin secretion. These effects are blocked by the alpha 2-adrenoceptor antagonist, yohimbine. 2. Pretreatment of rats with Bordetella pertussis toxin resulted in a reversal of the usual plasma glucose and insulin responses to intravenously administered lithium (4 mEq kg-1). There was a slow ...
Bacillus subtilis and the closely related species Bacillus pumilus and Bacillus licheniformis have periodically been suggested to play a role in the aetiology of food poisoning despite the fact that the organisms do not possess the genes associated with enteropathogenicity in Bacillus cereus. We show here that Bacillus mojavensis, an organism closely related to B. subtilis, is able to produce ...
We introduced disulfide bonds to lock the integrin ?L?2 I domain in predicted open, ligand binding or closed, nonbinding conformations. Transfectants expressing ?L?2 heterodimers containing locked-open but not locked-closed or wild-type I domains constitutively adhered to intercellular adhesion molecule-1 (ICAM-1) substrates. Locking the I domain closed abolished ...
Hepatocyte growth factor (HGF) activates the Met receptor tyrosine kinase by binding and promoting receptor dimerization. Here we describe a mechanistic basis for designing Met antagonists based on NK1, a natural variant of HGF containing the N-terminal and the first kringle domain. Through detailed biochemical and structural analyses, we demonstrate that both mouse and human NK1 induce Met ...
