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11.
The relationship between the susceptibility to convulsions, the content of pyridoxal 5'-phosphate and the activity of pyridoxal kinase (EC 2.7.1.35) and glutamate decarboxylase (EC 4.1.1.15) in brain, was studied in the developing mouse. Seizures were induced by pyridoxal phosphate-gamma-glutamyl hydrazone (PLPGH), a drug previously reported to reduce the levels of pyridoxal 5'-phosphate and as a consequence to inhibit the activity of glutamate decarboxylase in brain of adult mice. It was found that the seizure pattern, as well as the time of appearance of convulsions, differed between 2- and 5-day old mice and 10-day old or older mice, indicating a progressive increase in seizure susceptibility during development. In brain, pyridoxal kinase activity and pyridoxal 5'-phosphate levels were decreased by the administration of PLPGH at all ages studied, whereas glutamate decarboxylase activity was inhibited less than 25% in 2- and 5-day old mice, and about 50% thereafter. Parallelly, the activation of glutamate decarboxylase by pyridoxal 5'-phosphate added in vitro to control homogenates was less in 2- and 5-day old mice than in older animals. It is concluded that the increase in the susceptibility to seizures induced by PLPGH during development is probably related to the increase observed in the sensitivity of glutamate decarboxylase in vivo to a decrease of pyridoxal 5'-phosphate levels. The correlation between pyridoxal 5'-phosphate, glutamate decarboxylase, and seizure susceptibility seems to be established at about 10 days of age. 相似文献
12.
Some properties of glutamate decarboxylase (EC 4.1.1.15) activity in brain of newborn and adult mouse were studied comparatively. It was found that glutamate decarboxylase of the newborn brain was strongly inactivated by homogenization in hypotonic medium, centrifugation of isotonic sucrose homogenates, preincubation at 37°C or the addition of Triton-X-100, whereas the adult brain enzyme was practically unaffected by any of these conditions. It was also found that the newborn glutamate decarboxylase was less activated by pyridoxal 5′-phosphate and less inhibited by pyridoxal 5′-phosphate oxime-O-acetic acid, than the adult enzyme. These differences do not exist for brain dihydroxyphenylalanine decarboxylase (EC 4.1.1.26) and are not due to the release of inhibitors from the newborn brain. On the basis of the results obtained it is postulated that two forms of glutamate decarboxylase exist in brain: a newborn form, which is unstable and has high affinity for pyridoxal 5′-phosphate, and an adult form, which is much more stable and has low affinity for pyridoxal 5′-phosphate. The possible implications of these findings in the establishment of the σ-aminobutyric acid dependent synaptic inhibitory mechanisms during development are discussed. 相似文献
13.
Yefi R Ponce DP Niechi I Silva E Cabello P Rodriguez DA Marcelain K Armisen R Quest AF Tapia JC 《Journal of cellular biochemistry》2011,112(11):3167-3175
Augmented expression of protein kinase CK2 is associated with hyperproliferation and resistance to apoptosis in cancer cells. Effects of CK2 are at least partially linked to signaling via the Wnt/β-catenin pathway, which is dramatically enhanced in colon cancer. Cyclooxygenase-2 (COX-2), a Wnt/β-catenin target gene, has been associated with enhanced cancer progression and metastasis. However, the possibility that a connection may exist between CK2 and COX-2 has not been explored previously. Here we investigated changes in COX-2 expression and activity upon CK2 modulation and evaluated how these changes affected cell viability. COX-2 expression and cell viability decreased upon selective inhibition of COX-2 with SC-791 or CK2 with 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole (DMAT), both in human colon (HT29-ATCC, HT29-US, DLD-1) and breast (ZR-75) cancer cells, as well as in human embryonic kidney (HEK-293T) cells. On the other hand, ectopic CK2α expression promoted up-regulation of COX-2 by activating the Wnt/β-catenin pathway in HEK-293T cells. Noteworthy, over-expression of either CK2α, β-catenin or COX-2, as well as supplementation of the medium with prostaglandin E2 (PGE2), all were individually sufficient to overcome limitations in cell viability triggered by CK2 inhibition either upon addition of DMAT or over-expression of a dominant negative CK2α variant. Altogether, these findings provide new insight to the role of CK2 in cancer by up-regulating COX-2 expression and thereby PGE2 production. 相似文献
14.
15.
Pregnane X receptor-agonists down-regulate hepatic ATP-binding cassette transporter A1 and scavenger receptor class B type I 总被引:4,自引:0,他引:4
Sporstøl M Tapia G Malerød L Mousavi SA Berg T 《Biochemical and biophysical research communications》2005,331(4):1533-1541
Pregnane X receptor (PXR) is the molecular target for a wide variety of endogenous and xenobiotic compounds. It regulates the expression of genes central to the detoxification (cytochrome P-450 enzymes) and excretion (xenobiotic transporters) of potentially harmful compounds. The aim of the present investigation was to determine the role of PXR in regulation of high-density lipoprotein (HDL) cholesterol metabolism by studying its impact on ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) expression in hepatocytes. ABCA1 and SR-BI are major factors in the exchange of cholesterol between cells and HDL. Expression analyses were performed using Western blotting and quantitative real time RT-PCR. Luciferase reporter gene assays were used to measure promoter activities. Total cholesterol was measured enzymatically after lipid extraction (Folch's method). The expression of ABCA1 and SR-BI was inhibited by the PXR activators rifampicin and lithocholic acid (LCA) in HepG2 cells and pregnenolone 16alpha-carbonitrile (PCN) in primary rat hepatocytes. Thus, PXR appears to be a regulator of hepatic cholesterol transport by inhibiting genes central to cholesterol uptake (SR-BI) and efflux (ABCA1). 相似文献
16.
Functional significance of isoform diversification in the protocadherin gamma gene cluster 总被引:1,自引:0,他引:1
WV Chen FJ Alvarez JL Lefebvre B Friedman C Nwakeze E Geiman C Smith CA Thu JC Tapia B Tasic JR Sanes T Maniatis 《Neuron》2012,75(3):402-409
The mammalian Protocadherin (Pcdh) alpha, beta, and gamma gene clusters encode a large family of cadherin-like transmembrane proteins that are differentially expressed in individual neurons. The 22 isoforms of the Pcdhg gene cluster are diversified into A-, B-, and C-types, and the C-type isoforms differ from all other clustered Pcdhs in sequence and expression. Here, we show that mice lacking the three C-type isoforms are phenotypically indistinguishable from the Pcdhg null mutants, displaying virtually identical cellular and synaptic alterations resulting from neuronal apoptosis. By contrast, mice lacking three A-type isoforms exhibit no detectable phenotypes. Remarkably, however, genetically blocking apoptosis rescues the neonatal lethality of the C-type isoform knockouts, but not that of the Pcdhg null mutants. We conclude that the role of the Pcdhg gene cluster in neuronal survival is primarily, if not specifically, mediated by its C-type isoforms, whereas a separate role essential for postnatal development, likely in neuronal wiring, requires isoform diversity. 相似文献
17.
18.
G. Schmeda-Hirschmann J.A. Rodriguez C. Theoduloz S.L. Astudillo G.E. Feresin A. Tapia 《Free radical research》2013,47(4):447-452
The dry leaves of Peumus boldus (Monimiaceae) are used in infusion or decoction as a digestive and to improve hepatic complains. Preliminary assays showed free-radical scavenging activity in hot water extracts of boldo leaves, measured by the decoloration of a methanolic solution of the 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH). Assay-guided isolation led to the active compounds. Catechin proved to be the main free-radical scavenger of the extracts. Lipid peroxidation in erythrocytes was inhibited by boldo extracts and fractions at 500 w g/ml with higher effect for the ethyl acetate soluble and alkaloid fractions. The IC 50 for catechin and boldine in the lipid peroxidation test were 75.6 and 12.5 w g/ml, respectively. On the basis of dry starting material, the catechin content in the crude drug was 2.25% while the total alkaloid calculated as boldine was 0.06%. The activity of boldine was six times higher than catechin in the lipid peroxidation assay. However, the mean catechin:total alkaloid content ratio was 37:1. The relative concentration of alkaloids and phenolics in boldo leaves and their activity suggest that free-radical scavenging effect is mainly due to catechin and flavonoids and that antioxidant effect is mainly related with the catechin content. The high catechin content of boldo leaves and its bioactivity suggest that quality control of Boldo folium has to combine the analysis of catechin as well as their characteristic aporphine alkaloids. 相似文献
19.
Dasfne Lee‐Liu Gabriela Edwards‐Faret Víctor S. Tapia Juan Larraín 《Genesis (New York, N.Y. : 2000)》2013,51(8):529-544
Unlike mammals, regenerative model organisms such as amphibians and fish are capable of spinal cord regeneration after injury. Certain key differences between regenerative and nonregenerative organisms have been suggested as involved in promoting this process, such as the capacity for neurogenesis and axonal regeneration, which appear to be facilitated by favorable astroglial, inflammatory and immune responses. These traits provide a regenerative‐permissive environment that the mammalian spinal cord appears to be lacking. Evidence for the regenerative nonpermissive environment in mammals is given by the fact that they possess neural stem/progenitor cells, which transplanted into permissive environments are able to give rise to new neurons, whereas in the nonpermissive spinal cord they are unable to do so. We discuss the traits that are favorable for regeneration, comparing what happens in mammals with each regenerative organism, aiming to describe and identify the key differences that allow regeneration. This comparison should lead us toward finding how to promote regeneration in organisms that are unable to do so. genesis 51:529–544. © 2013 Wiley Periodicals, Inc. 相似文献
20.
Wayne Reeve Rui Tian Sofie De Meyer Vanessa Melino Jason Terpolilli Julie Ardley Ravi Tiwari John Howieson Ronald Yates Graham O’Hara Mohamed Ninawi Hazuki Teshima David Bruce Chris Detter Roxanne Tapia Cliff Han Chia-Lin Wei Marcel Huntemann James Han I-Min Chen Konstantinos Mavromatis Victor Markowitz Natalia Ivanova Galina Ovchinnikova Ioanna Pagani Amrita Pati Lynne Goodwin Sam Pitluck Tanja Woyke Nikos Kyrpides 《Standards in genomic sciences》2013,9(2):243-253
Rhizobium leguminosarum bv. trifolii strain TA1 is an aerobic, motile, Gram-negative, non-spore-forming rod that is an effective nitrogen fixing microsymbiont on the perennial clovers originating from Europe and the Mediterranean basin. TA1 however is ineffective with many annual and perennial clovers originating from Africa and America. Here we describe the features of R. leguminosarum bv. trifolii strain TA1, together with genome sequence information and annotation. The 8,618,824 bp high-quality-draft genome is arranged in a 6 scaffold of 32 contigs, contains 8,493 protein-coding genes and 83 RNA-only encoding genes, and is one of 20 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Community Sequencing Program. 相似文献