Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Investigations with the fluorinated spermidine analogues show clearly that these compounds have significant potential for studying the metabolism and functions of the polyamines. However, the biochemical and biological properties of these analogues are dissimilar. This is due to the influence of the fluorine substituent(s) on the basicity of the amine function proximal to the fluoromethylene group, this effect being amplified by geminal disubstitution. The monofluorinated spermidine analogues compare well with the natural amine in their ability to regulate the expression of the decarboxylase enzymes, to be substrates of spermine synthase and to support growth of polyamine-deficient cells. It is also likely that 6-monofluorospermine, formed biochemically in situ, shares with spermine similar functions. These findings raise the possibility of using these spermidine analogues to study the metabolism and pharmacology of polyamines in vivo but also to provide more insight into the regulatory role of spermidine in ODC and SAM-DC expression. Another potential application may be the use of these analogues as probes in tumor imaging and therapy control. This indication has been inferred by studies in tumor-bearing animals, using 19F-NMR spectroscopy determination of tissue fluorospermidine and fluorospermine, formed biochemically from the precursors 2-fluoro or 2,2-difluoroputrescine, and which demonstrate preferential accumulation in tumor versus normal tissue. Finally, these monofluorinated spermidine analogues may exert beneficial effects in pathological states associated with polyamine deficiency. These diseases remain however to be identified. Among the difluorinated spermidine analogues, 7,7-difluorospermidine possesses the most interesting properties. This spermidine analogue still possesses ODC and SAM-DC repressing activities although at much higher concentration than spermidine. More importantly it is a potent inhibitor of spermine synthesis both in cultured cells and in vivo due to its efficient competition with spermidine in the spermine synthase reaction. This compound not only depletes tumor cell of its spermine content but, in addition, appears to exert by itself and/or via 6,6-difluorospermine, the product of its metabolism, polyamine antagonist effects. Combined with MAP but also with DFMO, two potent irreversible inhibitors of ODC which block the synthesis of the natural endogenous polyamines, 7,7-difluorospermidine causes an immediate decrease of viability in cultured HTC cells and promotes tumor regression and stabilization in hepatoma-bearing rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fluorine-containing polyamines: biochemistry and potential applications. 307 45

A stochastic lateral signaling interaction between two developing Caenorhabditis elegans AWC olfactory neurons causes them to take on asymmetric patterns of odorant receptor expression, called AWC(OFF) and AWC(ON). Here we show that the AWC lateral signaling gene tir-1 (previously known as nsy-2) encodes a conserved post-synaptic protein that specifies the choice between AWC(OFF) and AWC(ON). Genetic evidence suggests that tir-1 acts downstream of a voltage-gated calcium channel and CaMKII (UNC-43) to regulate AWC asymmetry via the NSY-1(ASK1) p38/JNK MAP (mitogen-activated protein) kinase cascade. TIR-1 localizes NSY-1 to post-synaptic regions of AWC, and TIR-1 binds UNC-43, suggesting that it assembles a synaptic signaling complex that regulates odorant receptor expression. Temperature-shift experiments indicate that tir-1 affects AWC during a critical period late in embryogenesis, near the time of AWC synapse formation. TIR-1 is a multidomain protein with a TIR (Toll-interleukin-1 receptor) domain that activates signaling, SAM repeats that mediate localization to post-synaptic regions of axons, and an N-terminal inhibitory domain. TIR-1 and other TIR proteins are implicated in vertebrate and invertebrate innate immunity, as are NSY-1/ASK1 kinases, so this pathway may also have a conserved function in immune signaling.
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PMID:A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling. 1562 92

Hippocampal cholinergic neurostimulating peptide (HCNP), originally isolated from soluble fraction of young rat hippocampus and released from hippocampus by the stimulation of N-methyl-d-aspartate (NMDA) receptors, enhances the cholinergic phenotype development in vitro. HCNP precursor protein (HCNP-pp) has multiple functions, not only acting as the precursor of HCNP but also serving as an inhibitor of phosphorylation of Erk and contributing to neuronal growth and memory formation. In this study, the accumulation of HCNP and/or HCNP precursor in hippocampus was found to progress from 2 to 5 months of age in senescence-accelerated mouse-prone 8 (SAM P8). This HCNP surge in the hippocampus appears to correspond to the age of onset of memory deterioration, reduction of amount of NMDA-type receptor, and morphological aberration in this dementia model mouse, SAM P8. The present findings, together with our previously published results, suggest that the HCNP and/or HCNP precursor is involved in the dysfunction of the cholinergic neuronal system and memory deterioration in this model mouse via NMDA-type receptor signaling and the activation of the MAP cascade.
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PMID:Differential expression of HCNP-related antigens in hippocampus in senescence-accelerated mice. 1757 Mar 50

As a consequence of the "large p small n" characteristic for microarray data, hypothesis tests based on individual genes often result in low average power. There are several proposed tests that attempt to improve power. Among these, the FS test that was developed using the concept of James-Stein shrinkage to estimate the variances showed a striking average power improvement. In this paper, we establish a framework in which we model the key parameters with a distribution to find an optimal Bayes test which we call the MAP test (where MAP stands for Maximum Average Power). Under this framework, the FS test can be derived as an empirical Bayes test approximating the MAP test corresponding to modeling the variances. By modeling both the means and the variances with a distribution, a MAP statistic is derived which is optimal in terms of average power but is computationally intensive. An empirical Bayes test called the FSS test is derived as an approximation to the MAP tests and can be computed instantaneously. The FSS statistic shrinks both the means and the variances and has numerically identical average power to the MAP tests. Much numerical evidence is presented in this paper that shows that the proposed test performs uniformly better in average power than the other tests in the literature, including the classical F test, the FS test, the test of Wright and Simon, the moderated t-test, SAM, Efron's t test, the B-statistic and Storey's optimal discovery procedure. A theory is established which indicates that the proposed test is optimal in power when controlling the false discovery rate (FDR).
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PMID:Optimal tests shrinking both means and variances applicable to microarray data analysis. 2088 75