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61.
Dendritic Ca2+ plays an important role not only in synaptic integration and synaptic plasticity, but also in dendritic excitability in midbrain dopamine neurons. However, the functional organization of dendritic Ca2+ signals in the dopamine neurons remains largely unknown. We therefore investigated dendritic Ca2+ signals by measuring glutamate-induced Ca2+ increases along the dendrites of acutely isolated midbrain dopamine neurons.Maximal doses of glutamate induced a [Ca2+]c rise with similar amplitudes in proximal and distal dendritic regions of a dopamine neuron. Glutamate receptors contributed incrementally to the [Ca2+]c rise according to their distance from the soma, with a reciprocal decrement in the contribution of voltage-operated Ca2+ channels (VOCCs). The contribution of AMPA and NMDA receptors increased with dendritic length, but that of metabotropic glutamate receptors decreased. At low doses of glutamate at which spontaneous firing was sustained, the [Ca2+]c rise was higher in the distal than the proximal regions of a dendrite, possibly due to the increased spontaneous firing rate.These results indicate that functional organization of Ca2+ signals in the dendrites of dopamine neurons requires different combination of VOCCs and glutamate receptors according to dendritic length, and that regional Ca2+ rises in dendrites respond differently to applied glutamate concentration. 相似文献
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Kim JH Lee JO Lee SK Moon JW You GY Kim SJ Park SH Park JM Lim SY Suh PG Uhm KO Song MS Kim HS 《The Journal of biological chemistry》2011,286(9):7567-7576
Homocysteine sulfinic acid (HCSA) is a homologue of the amino acid cysteine and a selective metabotropic glutamate receptor (mGluR) agonist. However, the metabolic role of HCSA is poorly understood. In this study, we showed that HCSA and glutamate stimulated glucose uptake in C2C12 mouse myoblast cells and increased AMP-activated protein kinase (AMPK) phosphorylation. RT-PCR and Western blot analysis revealed that C2C12 expresses mGluR5. HCSA transiently increased the intracellular calcium concentration. Although α-methyl-4-carboxyphenylglycine, a metabotropic glutamate receptor antagonist, blocked the action of HCSA in intracellular calcium response and AMPK phosphorylation, 6-cyano-7-nitroquinoxaline-2,3-dione, an AMPA antagonist, did not exhibit such effects. Knockdown of mGluR5 with siRNA blocked HCSA-induced AMPK phosphorylation. Pretreatment of cells with STO-609, a calmodulin-dependent protein kinase kinase (CaMKK) inhibitor, blocked HCSA-induced AMPK phosphorylation, and knockdown of CaMKK blocked HCSA-induced AMPK phosphorylation. In addition, HCSA activated p38 mitogen-activated protein kinase (MAPK). Expression of dominant-negative AMPK suppressed HCSA-mediated phosphorylation of p38 MAPK, and inhibition of AMPK and p38 MAPK blocked HCSA-induced glucose uptake. Phosphorylation of protein kinase C ζ (PKCζ) was also increased by HCSA. Pharmacologic inhibition or knockdown of p38 MAPK blocked HCSA-induced PKCζ phosphorylation, and knockdown of PKCζ suppressed the HCSA-induced increase of cell surface GLUT4. The stimulatory effect of HCSA on cell surface GLUT4 was impaired in FITC-conjugated PKCζ siRNA-transfected cells. Together, the above results suggest that HCSA may have a beneficial role in glucose metabolism in skeletal muscle cells via stimulation of AMPK. 相似文献
63.
Ju-Won Kwak Hyobin Jeong Sun-Ho Han Youngkyu Kim Sung Min Son Inhee Mook-Jung Daehee Hwang Joon Won Park 《PloS one》2014,9(5)
Monitoring protein phosphorylation at the cellular level is important to understand the intracellular signaling. Among the phosphoproteomics methods, phosphokinase antibody arrays have emerged as preferred tools to measure well-characterized phosphorylation in the intracellular signaling. Here, we present a dendron-coated phosphokinase antibody array (DPA) in which the antibodies are immobilized on a dendron-coated glass slide. Self-assembly of conically shaped dendrons well-controlled in size and structure resulted in precisely controlled lateral spacing between the immobilized phosphosite-specific antibodies, leading to minimized steric hindrance and improved antigen-antibody binding kinetics. These features increased sensitivity, selectivity, and reproducibility in measured amounts of protein phosphorylation. To demonstrate the utility of the DPA, we generated the phosphorylation profiles of brain tissue samples obtained from Alzheimer''s disease (AD) model mice. The analysis of the profiles revealed signaling pathways deregulated during the course of AD progression. 相似文献
64.
Choi O Wu CZ Kang SY Ahn JS Uhm TB Hong YS 《Journal of industrial microbiology & biotechnology》2011,38(10):1657-1665
Biological synthesis of plant secondary metabolites has attracted increasing attention due to their proven or assumed beneficial
properties and health-promoting effects. Phenylpropanoids are the precursors to a range of important plant metabolites such
as the secondary metabolites belonging to the flavonoid/stilbenoid class of compounds. In this study, engineered Escherichia coli containing artificial phenylpropanoid biosynthetic pathways utilizing tyrosine as the initial precursor were established
for production of plant-specific metabolites such as ferulic acid, naringenin, and resveratrol. The construction of the artificial
pathway utilized tyrosine ammonia lyase and 4-coumarate 3-hydroxylase from Saccharothrix espanaensis, cinnamate/4-coumarate:coenzyme A ligase from Streptomyces coelicolor, caffeic acid O-methyltransferase and chalcone synthase from Arabidopsis thaliana, and stilbene synthase from Arachis hypogaea. 相似文献
65.
Receptor for advanced glycation endproducts (RAGE) is a transmembrane protein that belongs to the immunoglobulin superfamily.
RAGE is expressed ubiquitously-high in lung and moderate to low in a wide range of cells-in a tightly regulated manner at
various stages of development. RAGE is a pattern recognition receptor that binds to multiple ligands, including amphoterin,
members of the S100/calgranulin family, the integrin Mac-1, and amyloid β-peptide (Aβ). RAGE-ligand engagement effects the
activation of diverse cascades that initiate and stimulate chronic stress pathways and repair, depending on the ligand, environment,
and developmental stage. Further, RAGE-ligand interaction and the consequent upregulation of RAGE through a positive feedback
loop are often associated with various diseases, including vascular disease, diabetes, cancer, and neurodegenerative disease.
It is unknown how RAGE mediates these events, but such phenomena appear to be linked to the inflammatory response. In this
review, we summarize the findings on RAGE from published reports and ongoing studies. Also, the implication of RAGE in Alzheimer
disease, the most common neurodegenerative disease in the elderly population, will be discussed, with a focus on Aβ-RAGE interactions
with regard to signaling pathways and their impact on cellular activity. 相似文献
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We introduce a mesoscopic scale chemotaxis model for traveling wave phenomena which is induced by food metric. The organisms of this simplified kinetic model have two discrete velocity modes, \(\pm s\) and a constant tumbling rate. The main feature of the model is that the speed of organisms is constant \(s\,{>}\,0\) with respect to the food metric, not the Euclidean metric. The uniqueness and the existence of the traveling wave solution of the model are obtained. Unlike the classical logarithmic model case there exist traveling waves under super-linear consumption rates and infinite population pulse-type traveling waves are obtained. Numerical simulations are also provided. 相似文献
69.
R-stereoselective amidase from Rhodococcus erythropolis No. 7 acting on 4-chloro-3-hydroxybutyramide
Ethyl (S)-4-chloro-3-hydroxybutyrate is an intermediate for the synthesis of Atorvastatin, a chiral drug used for hypercholesterolemia. A Rhodococcus erythropolis strain (No. 7) able to convert 4-chloro-3-hydroxybutyronitrile into 4-chloro-3-hydroxybutyric acid has recently been isolated from soil. This activity has been regarded as having been caused by the successive actions of the nitrile hydratase and amidase. In this instance, the corresponding amidase gene was cloned from the R. erythropolis strain and expressed in Escherichia coli cells. A soluble active form of amidase enzyme was obtained at 18 degrees . The Ni column-purified recombinant amidase was found to have a specific activity of 3.89 U/mg toward the substrate isobutyramide. The amidase was found to exhibit a higher degree of activity when used with midchain substrates than with short-chain ones. Put differently, amongst the various amides tested, isobutyramide and butyramide were found to be hydrolyzed the most rapidly. In addition to amidase activity, the enzyme was found to exhibit acyltransferase activity when hydroxyl amine was present. This dual activity has also been observed in other enzymes belonging to the same amidase group (E.C. 3.5.1.4). Moreover, the purified enzyme was proven to be able to enantioselectively hydrolyze 4-chloro-3-hydroxybutyramide into the corresponding acid. The e.e. value was measured to be 52% when the conversion yield was 57%. Although this e.e. value is low for direct commercial use, molecular evolution could eventually result in this amidase being used as a biocatalyst for the production of ethyl (S)-4-chloro-3-hydroxybutyrate. 相似文献
70.
Bioactivity-directed fractionation of extracts from the seeds of Trichosanthes kirilowii led to the isolation of (-)-1-O-feruloylsecoisolariciresinol (2), named hanultarin, In addition, four known lignans were also isolated, including (-)-secoisolariciresinol (1), 1,4-O-diferuloylsecoisolariciresinol (3), (-)-pinoresinol (4), and 4-ketopinoresinol (5). Their structures were elucidated on the basis of spectroscopic data. Compounds 2 and 3 exhibited strong cytotoxic effects against human lung carcinoma A549 cells, melanoma SK-Mel-2 cells, and mouse skin melanoma B16F1 cells with IC(50) ranges of 3-13 microg/mL. Compound 2 showed an inhibitory effect on the polymerization of the actin cytoskeleton in normal epidermal keratinocyte (HaCaT cells), suggesting unique biological properties of compound 2 compared to those of the other isolates. 相似文献