Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An enzyme hydrolyzing diadenosine 5',5"'P1, P4-tetraphosphate (Ap4A) to AMP and ATP has been purified to apparent homogeneity from mouse liver cell extracts. The isolation procedure comprised ammonium sulfate precipitation, chromatography on Sephadex G-75. DEAE-cellulose, blue Sepharose and AMP-Sepharose. The enzyme is a single polypeptide chain with a native Mr = 64,000 with a Km of 1.66 microM and Vmax of 1.25 mumol/min. AMP, ADP, Ap4, GTP, Gp4, Ap3A, Ap5A, Gp3G, and Gp5G are noncompetitive inhibitors of the Ap4A hydrolase activity, whereas Gp4G inhibits Ap4A hydrolysis competitively with a Ki of 6 microM. Theophylline, caffeine, and isobutylmethylxanthine do not or only slightly inhibit Ap4A hydrolysis. Mitogenic factors have no effect on the enzymatic activity of Ap4A hydrolase, excluding that a direct influence of internalized mitogens on Ap4A degradation could be responsible for mitogen-dependent fluctuation of intracellular Ap4A pool sizes.
 ...
PMID:Diadenosine tetraphosphate hydrolase from mouse liver. Purification to homogeneity and partial characterization. 627 21

Caffeine-amphetamine interactions were studied to determine whether attenuation of amphetamine-induced activity by caffeine pretreatment (30 mg/kg) is the result of increased or decreased sensitivity to amphetamine. Caffeine pretreatment attenuated amphetamine activity in the rats without producing a horizontal shift in the dose-response curve. Results support a reduction in sensitivity to amphetamine. A cross-tolerance design revealed an asymmetrical interaction between caffeine and amphetamine. Multiple caffeine treatments (30 mg/kg) produced tolerance and attenuation of subsequent amphetamine activity (1.5 mg/kg). Amphetamine did not produce tolerance or affect subsequent caffeine-induced activity.
 ...
PMID:Caffeine reduces amphetamine-induced activity in asymmetrical interaction. 670 74

DNA and protein contents of pairs of sister nuclei were determined using a combined Feulgen-dinitrofluorobenzene technique. Sister nuclei were studied in binucleate cells, induced by treatment with 0.1% caffeine, and in sister mononucleate cells of untreated roots. Excised pea roots, grown in culture, were treated with 5-aminouracil to induce mitotic synchrony and with caffeine at the time of peak mitotic index, to provide the maximum number of binucleate cells. The induced binucleate cells form a marked population which was followed through a cell cycle; sister nuclei showed a correlation of volume and protein content, r = 0.79. Protein contents of sister nuclei were rarely identical and at 1 + 2 and 1 + 6 h the difference in protein contents of sister nuclei was significant (p = 0.05). Mean nuclear protein content decreased from 1 + 2 to 1 + 6 h; then, as nuclei entered S phase, their protein content increased. From 1 + 2 to 1 + 14 h the increase in protein content, in absolute amount, was identical in both sister nuclei. This suggests that there was a biphasic pattern of protein uptake; it is differential, in sister nuclei, in the first part of G1 but is identical throughout the rest of interphase. Analysis of sister nuclei from sister mononucleate cells showed a similar pattern of change; this is further evidence, from untreated cells, of a biophasic pattern of protein uptake. Caffeine-treated nuclei had lower protein contents than untreated nuclei, yet they completed a cell cycle and entered mitosis; this suggests that nonessential proteins were no longer present. It is proposed that mitosis is asymmetrical for molecules that regulate rates of macromolecular synthesis, cell growth, and progress through a cell cycle and that once the initial asymmetry has been established, it is maintained throughout interphase, even in binucleate cells in which the two nuclei share a common cytoplasm.
 ...
PMID:Differences in protein content of sister nuclei: evidence from binucleate and mononucleate cells. 708 48

A soluble 12-kDa FK506 binding protein (FKBP12), the cellular receptor of the immunosuppressive drug FK506, is tightly associated with the Ca2+ release channel of rabbit skeletal muscle sarcoplasmic reticulum [Jayaraman, T., Brillantes, A. M., Timerman, A. P., Fleischer, S., Erdjument-Bromage, H., Tempst, P. & Marks, A. (1992) J. Biol. Chem. 267, 9474-9477]. We have assessed the role of excess free FKBP12 in the function of single Ca2+ release channels incorporated into planar lipid bilayers. The addition of human recombinant FKBP12 (hFKBP12) to the cytoplasmic face of the Ca2+ release channel blocked the flow of cytoplasmic to luminal current (outward current) in a concentration-dependent manner but had no significant effect on the flow of luminal to cytoplasmic current (inward current). The luminal to cytoplasmic flow of current was modulated by Ca2+, Mg2+, ATP, caffeine, and ryanodine in the presence and absence of FKBP12. An immunosuppressive drug, L-683,590, an analog of FK506, did not block or reverse the asymmetrical hFKBP12 blockade of single Ca2+ release channels in planar lipid bilayers. FKBP12 may play a role in regulation of the flow of ions into the lumen of the sarcoplasmic reticulum through the Ca2+ release channel.
 ...
PMID:Asymmetrical blockade of the Ca2+ release channel (ryanodine receptor) by 12-kDa FK506 binding protein. 752 48

In the present study, we investigated taste-taste, taste-vehicle, and simultaneous taste-vehicle-taste mixtures. Subjects made estimates of the sweetness and bitterness of 27 stimuli. Sucrose (292, 585, and 1170 mM), caffeine (13, 26, and 52 mM), and binary mixtures of low (292-13 mM), middle (585-26 mM), and high (1170-52 mM) levels of both components were dispersed in water, carboxymethylcellulose (CMC) 1% w/v, and gelatin 6% w/v. The sweetness and bitterness of the sucrose-vehicle-caffeine combinations were significantly weaker than the respective sucrose-vehicle and caffeine-vehicle combinations. The emerged mutual suppressive effects were asymmetrical and persisted when both tastants were presented in CMC and gelatin. Moreover, the increase in vehicle consistency and the simultaneous addition of another taste reduced the perceived intensity of a taste either presented alone or dissolved in water. For both sweetness and bitterness, the total taste suppression observed was always significant.
 ...
PMID:Perception of sweetness and bitterness in different vehicles. 813 44

Hyperactivated sperm motility is characterized by high-amplitude and asymmetrical flagellar beating that assists sperm in penetrating the oocyte zona pellucida. Other functional changes in sperm, such as activation of motility and capacitation, involve cross talk between the cAMP/PKA and tyrosine kinase/phosphatase signaling pathways. Our objective was to determine the role of the cAMP/protein kinase A (PKA) signaling pathway in hyperactivation. Western blot analyses of detergent extracts of whole sperm and flagella were performed using antiphosphotyrosine antibody. Bull sperm capacitated by 10 microg/ml heparin and/or 1 mM dibutyryl-cAMP plus 100 microM 3-isobutyl-1-methylxanthine exhibited increased protein tyrosine phosphorylation without becoming hyperactivated. Procaine (5 mM) or caffeine (10 mM) immediately induced hyperactivation in nearly 100% of motile sperm but did not increase protein tyrosine phosphorylation. After 4 h of incubation with caffeine, sperm expressed capacitation-associated protein tyrosine phosphorylation but hyperactivation was significantly reduced. Sperm initially hyperactivated by procaine or caffeine remained hyperactivated for at least 4 h in the presence of Rp-cAMPS (cAMP antagonist) or PKA inhibitors H-89 or H-8. Pretreatment with inhibitors also failed to block induction of hyperactivation; however, the inhibitors did block protein tyrosine phosphorylation when sperm were incubated with capacitating agents, thereby verifying inhibition of the cAMP/PKA pathway. While induction of hyperactivation did not depend on cAMP/PKA, it did require extracellular Ca(2+). These findings indicate that hyperactivation is mediated by a Ca(2+) signaling pathway that is separate or divergent from the pathway associated with acquisition of acrosomal responsiveness and does not involve protein tyrosine phosphorylation downstream of the actions of procaine or caffeine.
 ...
PMID:Different signaling pathways in bovine sperm regulate capacitation and hyperactivation. 1476 20

Digital image analysis of the flagellar movements of cynomolgus macaque spermatozoa hyperactivated by caffeine and cAMP was carried out to understand the change in flagellar movements during hyperactivation. The degree of flagellar bending increased remarkably after hyperactivation, especially at the base of the midpiece. Mainly two beating patterns were seen in the hyperactivated monkey sperm flagella: remarkably asymmetrical flagellar bends of large amplitude and relatively symmetrical flagellar bends of large amplitude. The asymmetrical bends were often seen in the early stage of hyperactivation, whereas the symmetrical bends executed nonprogressive, figure-of-eight movement. Beat frequency of the hyperactivated spermatozoa significantly decreased while wavelength of flagellar waves roughly doubled. To determine the conditions under which the axonemes of hyperactivated sperm flagella have asymmetrical or symmetrical bends, the plasma membranes of monkey spermatozoa were extracted with Triton X-100 and motility was reactivated with MgATP(2-) under various conditions. The asymmetrical flagellar bends were brought about by Ca(2+), whereas the symmetrical flagellar bends resulted from low levels of Ca(2+) and high levels of cAMP. Under these conditions, beat frequency and wavelength of flagellar waves of demembranated, reactivated spermatozoa were similar to those of the hyperactivated spermatozoa. These results suggest that during hyperactivation of monkey spermatozoa intracellular Ca(2+) concentrations first rise, and then decrease while cAMP concentrations increase simultaneously.
 ...
PMID:Hyperactivation of monkey spermatozoa is triggered by Ca2+ and completed by cAMP. 1680 84

Aneuploidy has been implicated as an important step leading to various neoplasias. Although genetic factors that block aneuploidy have been the subject of intense interest, the impact of pharmacological and environmental substances on the development of aneuploidy has not been studied. Here, we show that caffeine induces aneuploidy through asymmetrical cell division. Mitotic exits of HeLa, U2OS, and primary fibroblast cells were significantly delayed by 10 mmol/L caffeine. Most caffeine-treated mitotic cells showed misalignment of chromosomes at the metaphase plates, and were arrested at prometaphase. Mitoticarrest deficient 2 (MAD2) depletion rescued the caffeine-induced delay of mitotic exit, indicating that caffeine-induced prolongation of mitosis was caused by activation of a MAD2-dependent spindle checkpoint. Enumeration of centromeres by fluorescence in situ hybridization revealed that cell division in the presence of caffeine was not symmetrical and resulted in aneuploid cell production. Most of these cells survived and underwent DNA synthesis. Our findings reveal a novel pharmacological effect of a high concentration of caffeine on genomic stability in dividing cells.
 ...
PMID:Caffeine yields aneuploidy through asymmetrical cell division caused by misalignment of chromosomes. 1875 64

Caffeine has been an integral component of our diet and medicines for centuries. It is now known that over consumption of caffeine has detrimental effects on our health, and also disrupts normal foetal development in pregnant mothers. In this study, we investigated the potential teratogenic effect of caffeine over-exposure on eye development in the early chick embryo. Firstly, we demonstrated that caffeine exposure caused chick embryos to develop asymmetrical microphthalmia and induced the orbital bone to develop abnormally. Secondly, caffeine exposure perturbed Pax6 expression in the retina of the developing eye. In addition, it perturbed the migration of HNK-1(+) cranial neural crest cells. Pax6 is an important gene that regulates eye development, so altering the expression of this gene might be the cause for the abnormal eye development. Thirdly, we found that reactive oxygen species (ROS) production was significantly increased in eye tissues following caffeine treatment, and that the addition of anti-oxidant vitamin C could rescue the eyes from developing abnormally in the presence of caffeine. This suggests that excess ROS induced by caffeine is one of the mechanisms involved in the teratogenic alterations observed in the eye during embryogenesis. In sum, our experiments in the chick embryo demonstrated that caffeine is a potential teratogen. It causes asymmetrical microphthalmia to develop by increasing ROS production and perturbs Pax6 expression.
...
PMID:Excess caffeine exposure impairs eye development during chick embryogenesis. 2463 5