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

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Query: KEGG:D01453 (caffeine)
21,611 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

X-Ray-induced chromosomal aberrations (CA) were potentiated by post-treatments in G2 with either caffeine (caff) or poly-D-lysine (PDL) in root-tip cells of Allium cepa. The enhancement of the yield of CA was concomitant with an increase in the frequency of mitosis. Our results seem to support the idea of a direct relationship between radiation-induced G2 delay and repair of chromosome damage. Here we report on similarities between caffeine and PDL in both decreasing G2 delay and enhancing chromatid aberration yield. The possible molecular mechanism(s) of action responsible for the cytogenetic effects observed are discussed.
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PMID:A comparative study of the potentiating effect of caffeine and poly-D-lysine on chromosome damage induced by X-rays in plant cells. 137 31

A number of reports suggest that the role of radiation-induced G2 arrest is to allow repair of potentially lethal damage in the cells before it comes to mitosis. Though the exact nature of the damage undergoing repair during the delayed G2 is not known, the yield of chromosomal aberrations observed in metaphase seems to be a good parameter to predict reproductive death of cells. In a previous paper, we have shown that poly-D-lysine, acting in a fashion reminiscent of that of caffeine in mammalian cells, is able to induce a premature onset of mitosis concomitant with an increase in the frequency of chromosomal aberrations in mutagen-treated plant cells. Cultured CHO cells were pre-exposed to either X-rays or mitomycin C and given different doses of the polycationic compound during G2 in order to analyze any effect on the frequency of chromatid-type aberrations as well as any modification of cell-cycle kinetics. A potentiation of chromosome damage and a premature arrival at mitosis were observed for both mutagens, though the effect was more evident in X-irradiated cells.
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PMID:Poly-D-lysine in G2 potentiates chromosome damage induced by X-rays and mitomycin C in CHO cells. 137 44

The low-molecular-weight peptide protease inhibitors, tosyl-lysine-chloromethyl ketone, antipain and leupeptin, inhibited poly(ADP-ribose) [poly(ADP-Rib)] polymerase in permeable cells. The concentrations required for 50% inhibition were 3.6, 5 and 29 mM, respectively. Two peptides without protease inhibitor activity, fibrinopeptide A and phenylalanine-leucine-(glutamine)2-leucine, also inhibited poly (ADP-Rib) synthesis; doses required for 50% inhibition were 0.37 and 11.2 mM, respectively. These concentrations lie within a range bracketed by the 50% inhibition concentrations of the strong and weak poly(ADP-Rib) synthesis inhibitors, 3-amino-benzamide (0.15 mM) and caffeine (greater than 100 mM), respectively. N-Ethylmaleimide also inhibited poly(ADP-Rib) synthesis, at a 50% inhibitory dose of 0.3 mM, in the absence of exogenous thiol reagents. High-molecular-weight protease inhibitors, such as soybean (including Bowman-Birk reagent) and lima bean trypsin inhibitors and human alpha 1-protease inhibitor, had no effect on poly(ADP-Rib) synthesis up to 2 mg/ml. Interference with transformation and other cellular effects that have been reported in carcinogen-damaged cells treated with low-molecular-weight peptide protease inhibitors may therefore involve common mechanisms with poly(ADP-Rib) inhibitors. Similar effects of high-molecular-weight protease inhibitors presumably involve different mechanisms.
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PMID:Some protease inhibitors are also inhibitors of poly(ADP-ribose) polymerase. 308 Dec 73

Synthetic [8-arginine]-vasopressin, [8-lysine]-vasopressin, [8-ornithine]-vasopressin or [2-phenylalanine, 8-lysine]-vasopressin aggregated human platelets in heparinized platelet-rich plasma. The lowest effective concentrations (1-4mU/ml) caused a primary transient aggregation, while higher concentrations also caused a secondary irreversible aggregation. Vasopressin was almost inactive in citrated platelet-rich plasma but caused aggregation in recalcified citrated or native material. Vasopressin also aggregated washed human platelets suspended in buffered saline, if fibrinogen and either Ca2+ or Mg2+ ions were present. Ethylene glycol-bis (beta-aminoethyl ether)-N,N'-tetraacetic acid inhibited aggregation completely but only after preincubation with the platelets, suggesting that platelet-bound calcium was also required. Phosphocreatine with creatine phosphokinase partially inhibited primary aggregation of platelets by vasopressin and prevented secondary aggregation, which suggests that release of platelet ADP contributed to these processes. Concentrations of vasopressin causing irreversible aggregation released small amounts of 14C from platelets containing serotonin-14C. Platelet aggregation induced by vasopressin was inhibited by adenosine, prostaglandin E1, N6,2'-0-dibutyryl cyclic 3',5'-AMP, caffeine, imipramine, or N-ethylmaleimide. Adenosine and prostaglandin E each inhibited the action of vasopressin much more powerfully than that of ADP and, therefore, cannot act solely by inhibiting the effects of the ADP released. In several respects the effect of vasopressin on blood platelets resembled its action on smooth muscle.
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PMID:Aggregation of human blood platelets by vasopressin. 434 80

Caffeine induced a state of G(1) arrest when added to an exponentially growing culture of Chinese hamster cells (line CHO). In addition to its effect on cell-cycle traverse, caffeine ameliorated a number of the responses of cells to ionizing radiation. The duration of the division delay period following X-irradiation of caffeine-treated cells was reduced, and the magnitude of reduction was dependent on caffeine concentration. Cells irradiated during the DNA synthetic phase in the presence of caffeine were delayed less in their exit from S, measured autoradiographically, and the radiation-induced reduction of radioactive thymidine incorporation into DNA was lessened. Cells synchronized by isoleucine deprivation, while being generally less sensitive to the effects of ionizing radiation than mitotically synchronized cells, were equally responsive to the effects of caffeine. The X-ray-induced reduction of phosphorylation of lysine-rich histone F1 was less in caffeine-treated cells than in untreated cells. Finally, survival after irradiation was only slightly reduced in caffeine-treated cells. A possible role of cyclic AMP in cell-cycle traverse of irradiated cells is discussed.
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PMID:Effects of caffeine on radiation-induced phenomena associated with cell-cycle traverse of mammalian cells. 436 Feb 69

The potencies of caffeine, theophylline, lysine-theophylline and 3-isobutyl-1-methylxanthine (IBMX) in stimulating sperm motility have been compared, and we have found IBMX to be significantly more potent than the other three compounds, which did not exhibit significant differences in potency from each other.
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PMID:The stimulatory effects of caffeine, theophylline, lysine-theophylline and 3-isobutyl-1-methylxanthine on human sperm motility. 620 49

This study reports that chick dorsal root ganglion neurites undergo a rapid (20 min) reorientation of their direction of growth in response to nerve growth factor (NGF) concentration gradients in vitro. Dorsal root ganglia from chick embryos were explanted onto a collagen-poly-L-lysine substrate. After 24-48 h in culture, NGF gradients were applied to individual growth cones via a micropipette containing 50 biological units NGF/ml. The growth cones turned and grew toward these NGF sources. This turning response was not caused by the trophic effects of NGF on neurite initiation, survival, or growth rate. Dorsal root neurites also grew toward sources of mono- and dibutyryl cyclic adenosine monophosphate (dB cAMP), cyclic guanosine monophosphate (cGMP), and elevated calcium in the presence of the calcium ionophore A23187. These results are consistent with the hypothesis that intracellular levels of cAMP and /or cGMP and calcium may play a role in the turning response of dorsal root neurites toward NGF, but do not establish a causal relationship between the mechanisms of action of NGF, cyclic nucleotides and calcium. Total growth cone adherence to the substrate was measured using a timed microjet of perfusion medium. NGF increased the adherence of growth cones to the substrate, but caffeine and dB cAMP which also elicit the positive turning response, decreased growth cone adherence. Calcium, which did not elicit the positive turning response, produced a greater growth cone adherence to the substrate than that observed with NGF. Although these results do not rule out a role of adhesion changes in axonal turning to NGF, they show that a general increase in adherence does not correlate well with the rapid turning response observed in this study.
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PMID:Characterization of the turning response of dorsal root neurites toward nerve growth factor. 625 25

Mate, an infusion containing caffeine (3 g/liter), is drunk hot by most Uruguayan, North Argentinian, and South Brazilian people. This beverage has been recently associated with esophageal cancer in Brazil and Uruguay. To test the mutagenic and lethal effects of mate infusion, caffeine, hyperthermia, and their combinations, we used Saccharomyces cerevisiae as an eucaryotic model system measuring lys to LYS reversions. We showed that mate infusion was not mutagenic, whereas caffeine at the same concentration contained in mate, produced a 5-fold increase in the spontaneous mutation rate. The highest observed mutagenic rate corresponded to hyperthermia (54 degrees C at 60 min). Hot caffeine also produced a time-dependent mutagenic effect, whereas hot mate infusion determined a significantly lower mutagenic effect than hot caffeine. The differential lethality produced by the tested agents plays an important role in the expression of the induced mutagenic damage. Caffeine and mate infusion could decrease the mutagenic effect of hyperthermia through the channeling of part of the induced DNA lesions into an error-free repair pathway.
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PMID:Mutagenicity induced by hyperthermia, hot mate infusion, and hot caffeine in Saccharomyces cerevisiae. 824 32

Distinct chemical cues acting on chemosensory structures on the dorsal lip of bloodsucking leeches activate the entire complement of appetitive and ingestive feeding behaviors. However, it is not known whether the maintenance of ingestion depends on continuous stimulation of these peripheral chemosensors. Leeches of the species Hirudo medicinalis and Macrobdella decora were fed for 2 min on an artificial blood solution containing 150 mM NaCl/1 mM arginine before switching the feeding solution to various experimental mixtures. Leeches did not start to feed on, but continued to ingest solutions in which equiosmolar KCl or lysine substituted for NaCl or arginine, respectively, until sated. In contrast, they rejected water and dropped off the feeding apparatus within 30 s of the exchange. Leeches also detached from the feeding tube when quinine, denatonium, or caffeine were added to the NaCl/arginine solution during an ongoing feeding bout. The duration of ingestion following the switch correlated inversely with the concentration of the drugs (0.1-10 mM). Superfusion of the dorsal lip with high concentrations of the bitter chemicals, while feeding was in progress, had no effect on the duration of ingestion. However, injections of the bitter substances directly into the gut, during a feeding bout, abruptly stopped ingestion. The results suggest that while leeches continue to sample their food once ingestion has begun, secondary chemosensory mechanisms situated downstream from the dorsal lip may be involved in the maintenance of ingestion and the rapid postingestive rejection of noxious foods.
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PMID:Postingestive chemosensation and feeding by leeches. 1060 32

In previous studies we demonstrated that histone preparations possess multiple effects in vivo on pituitary hormone secretion. We have now studied the specificity and signal transduction pathways involved in the prolactin (PRL)-releasing activity of histones H2A and H2B on perifused and incubated rat pituitary cells. In the perifusion experiments, freshly dispersed pituitary cells were packed into short columns and were continuously perifused with serum-free medium. The substances to be tested (stimuli) were pumped through the perifusion circuit, at the end of which perifusate fractions were collected and PRL measured by specific RIA. In the incubation studies, freshly dispersed pituitary cells were incubated in a metabolic incubator with different stimuli at different doses and for varying times. Perifusion of cells with median eminence extract (1/30), histone H2A (30 microM) or histone H2B (30 microM), generated clear PRL release responses. Cells incubated with histone H2A and H2B showed a dose- and time-dependent stimulatory effect on PRL release which, for H2A, was blocked by peptide MB-35, an 86-120 amino acid synthetic fragment of histone H2A. The polycation, poly-lys was unable to mimic the action of histones. To detect the possible signal transduction pathways involved in the response of lactotrophs to histones, cells were incubated with the calcium ionophore A23187, the calcium chelator EGTA, the intracellular phosphoinositide enhancer LiCl, the intracellular cAMP enhancers caffeine, NaF and forskolin, and the protein kinase C inhibitor, trifluoperazine (TFP). Both EGTA (or EGTA plus A23187 ionophore) and TFP were able to reduce significantly the response of lactotrophs to histones. Our results confirm previous evidence that histones may act as hypophysotropic signals. The data also suggest that calcium- and diacylglycerol-associated pathways participate in these effects.
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PMID:Studies on the prolactin-releasing mechanism of histones H2A and H2B. 1082 47


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