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161.
Mariana G. Todorova Esther Fuentes Bernat Soria Angel Nadal Ivan Quesada 《Cellular signalling》2009,21(4):523-528
Embryonic stem cells (ESC) are pluripotent and could be maintained in vitro in a self-renewing state indefinitely, at the same time preserving their potential to differentiate towards more specific lineages. Despite the progress in the field, the complex network of signalling cascades involved in the maintenance of the self-renewing and pluripotent state remains not fully understood. In the present study, we have investigated the role of lysophosphatidic acid (LPA), a potent mitogen present in serum, in Ca2+ signalling and early gene activation in mouse ESC (mESC). In these cells, we detected the expression of the G-protein coupled LPA receptor subtypes LPA1, LPA2 and LPA3. Using fluorescence Ca2+ imaging techniques, we showed that LPA induced an increase in intracellular Ca2+ concentration. This increase was also observed in the absence of extracellular Ca2+, suggesting the involvement of internal stores. Pre-treatment with BAPTA-AM, thapsigargin or U-73122 efficiently blocked this Ca2+ release, indicating that LPA was evoking Ca2+ mobilization from the endoplasmic reticulum via the phospholipase C (PLC) pathway. Interestingly, this signalling cascade initiated by LPA was involved in inducing the expression of the Ca2+-dependent early response gene c-myc, a key gene implicated in ESC self-renewal and pluripotency. Additionally, LPA increased the proliferation rate of mESC. Our findings therefore outline the physiological role of LPA in mESC. 相似文献
162.
Dessislava Todorova Todor Genkov Irina Vaseva-Gemisheva Vera Alexieva Emanuil Karanov Aileen Smith Michael Hall 《Acta Physiologiae Plantarum》2005,27(1):13-18
The levels of three endogenous cytokinin equivalents: zeatin (Z), iso-pentenyladenine (iP) and dihydrozeatin (dZ) in two Arabidopsis thaliana (L.) Heynh genotypes — wild type (wt) and ethylene-insensitive mutant (eti5), were compared using enzyme immunoassay (ELISA). Cytokinin content was measured after exposure to low (4 °C for 24 h in
darkness) or high temperature (38 °C for 24 h in darkness). Measurements were performed immediately and 24, 48 and 120 h after
treatments. It was found that at normal growth conditions eti5 plants contained more endogenous cytokinins compared to the wild type. At both temperature treatments mutant plants had decreased
total cytokinin levels. Wild-type plants treated with high temperature (HT) exhibited reduced total cytokinins (with the exception
of rates at 48 h), while low temperature (LT) treatment resulted in elevated total amount of the studied equivalents (except
at 24 h). The obtained results suggested that HT had greater effect on cytokinin levels than LT since it caused more profound
changes in the total content. We assume that this was due to the natural chilling tolerance of Arabidopsis plants. 相似文献
163.
164.
Futagami S Hiratsuka T Shindo T Horie A Hamamoto T Suzuki K Kusunoki M Miyake K Gudis K Crowe SE Tsukui T Sakamoto C 《Helicobacter》2008,13(3):209-218
Background and Aim: Apurinic/apyrimidinic endonuclease‐1 (APE‐1) is a key enzyme in DNA base excision repair (BER), linked to cancer chemosensitivity. However, little is known about the localization of APE‐1 in Helicobacter pylori‐infected gastric mucosa or its role in the development of gastric cancer. To investigate the role of APE‐1 in the development of gastric cancer, we examined APE‐1 expression and localization in cultured cells and gastric biopsies from patients with H. pylori‐infected gastritis or gastric adenoma, and from surgically resected gastric cancer. Methods: APE‐1 mRNA and protein expression were determined in H. pylori (CagA+) water‐extract protein (HPWEP)‐stimulated MKN‐28 cells, gastric adenocarcinoma cell‐line (AGS) cells, and human peripheral macrophages by real‐time polymerase chain reaction and Western blot analysis. APE‐1 expression and 8‐OHdG as a measure of oxidative DNA damage were evaluated by immunostaining. Localization of APE‐1 and IκBα phosphorylation in gastric adenoma and gastric cancer tissues were evaluated by single‐ and double‐label immunohistochemistry. Results: In studies in vitro, HPWEP‐stimulation significantly increased APE‐1 mRNA expression levels in both MKN‐28 cells and human peripheral macrophages. Hypo/reoxygenation treatment significantly increased APE‐1 protein expression in HPWEP‐stimulated MKN‐28 cells. HPWEP stimulation significantly increased both APE‐1 expression and IκBα phosphorylation levels in MKN‐28 and AGS cells. In human tissues, APE‐1 expression in H. pylori‐infected gastritis without goblet cell metaplasia was significantly increased as compared to that in tissues from uninfected subjects. Eradication therapy significantly reduced both APE‐1 and 8‐OHdG expression levels in the gastric mucosa. APE‐1 expression was mainly localized in epithelial cells within gastric adenoma and in mesenchymal cells of gastric cancer tissues. APE‐1 expression in gastric cancer tissues was significantly reduced compared to that in H. pylori‐infected gastric adenoma, while 8‐OHdG index and IκBα phosphorylation levels did not differ between these two neoplastic tissue types. Co‐localization of APE‐1 and IκBα phosphorylation was observed not in gastric cancer cells but in gastric adenoma cells. Conclusion: H. pylori infection is associated with increased APE‐1 expression in human cell lines and in gastric tissues from subjects with gastritis and gastric adenomas. The observed distinct expression patterns of APE‐1 and 8‐OHdG in gastric adenoma and gastric cancer tissues may provide insight into the progression of these conditions and warrants further investigation. 相似文献
165.
Grenz A Osswald H Eckle T Yang D Zhang H Tran ZV Klingel K Ravid K Eltzschig HK 《PLoS medicine》2008,5(6):e137
Background
Acute renal failure from ischemia significantly contributes to morbidity and mortality in clinical settings, and strategies to improve renal resistance to ischemia are urgently needed. Here, we identified a novel pathway of renal protection from ischemia using ischemic preconditioning (IP).Methods and Findings
For this purpose, we utilized a recently developed model of renal ischemia and IP via a hanging weight system that allows repeated and atraumatic occlusion of the renal artery in mice, followed by measurements of specific parameters or renal functions. Studies in gene-targeted mice for each individual adenosine receptor (AR) confirmed renal protection by IP in A1−/−, A2A−/−, or A3AR−/− mice. In contrast, protection from ischemia was abolished in A2BAR−/− mice. This protection was associated with corresponding changes in tissue inflammation and nitric oxide production. In accordance, the A2BAR-antagonist PSB1115 blocked renal protection by IP, while treatment with the selective A2BAR-agonist BAY 60–6583 dramatically improved renal function and histology following ischemia alone. Using an A2BAR-reporter model, we found exclusive expression of A2BARs within the reno-vasculature. Studies using A2BAR bone-marrow chimera conferred kidney protection selectively to renal A2BARs.Conclusions
These results identify the A2BAR as a novel therapeutic target for providing potent protection from renal ischemia. 相似文献166.
Liu L Brown D McKee M Lebrasseur NK Yang D Albrecht KH Ravid K Pilch PF 《Cell metabolism》2008,8(4):310-317
Caveolae are specialized invaginations of the plasma membrane found in numerous cell types. They have been implicated as playing a role in a variety of physiological processes and are typically characterized by their association with the caveolin family of proteins. We show here by means of targeted gene disruption in mice that a distinct caveolae-associated protein, Cavin/PTRF, is an essential component of caveolae. Animals lacking Cavin have no morphologically detectable caveolae in any cell type examined and have markedly diminished protein expression of all three caveolin isoforms while retaining normal or above normal caveolin mRNA expression. Cavin-knockout mice are viable and of normal weight but have higher circulating triglyceride levels, significantly reduced adipose tissue mass, glucose intolerance, and hyperinsulinemia--characteristics that constitute a lipodystrophic phenotype. Our results underscore the multiorgan role of caveolae in metabolic regulation and the obligate presence of Cavin for caveolae formation. 相似文献
167.
Effect of Ethylene and its Antagonist 1-MCP on the Senescence of Detached Leaves of Arabidopsis thaliana 总被引:2,自引:1,他引:1
V.S. Alexieva I.G. Sergiev D.A. Todorova E.N. Karanov A.R. Smith M.A. Hall 《Biologia Plantarum》2004,48(4):593-595
1-Methylcyclopropene (1-MCP) applied alone did not influence significantly the chlorophyll and carotenoid content of the older leaves of Arabidopsis thaliana (L.) Heynh., but retarded the senescence of the younger ones (6th and 7th leaf nodes). However, 1-MCP effectively blocks the ethylene induced senescence of excised rosette leaves. The preliminary application of 1-MCP (3 h in advance to the treatment by Ethrel) almost totally eliminated the ethylene action. Similar trend was also observed after simultaneous application of Ethrel and 1-MCP, and the effects of both treatments on the chlorophyll and carotenoid destruction are comparable. 相似文献
168.
Batovska DI Todorova IT Nedelcheva DV Parushev SP Atanassov AI Hvarleva TD Djakova GJ Bankova VS Popov SS 《Journal of plant physiology》2008,165(8):791-795
We examined the leaf chemical composition of six seedlings obtained by self-pollination of the Bulgarian wine-making variety Storgozia as well as the cultivar Bouquet, which is the susceptible parent of Storgozia. The chemical composition was investigated in the framework of a program for identification of metabolites associated with disease resistance in grape-vine. Acetone, dichloromethane and butanol extracts, as well as volatiles obtained from fresh material were analyzed by GC/MS. Based on the correlations of the GC/MS data and estimated resistance of the leaves towards the etiological agents of powdery mildew, downy mildew and botrytis as biomarkers for the fungal resistance, we proposed 16 individual metabolites – - and γ-tocopherol, squalene, -amyrine, stigmasta-3,5-diene-7-one, hexahydrofarnesyl acetone, glycolic acid, 3-hydroxybutanoic acid, 3-hydroxycaproic acid, malic acid, tartaric acid, erythronic acid, arabinoic acid, monoethyl phosphate, undecyl laurate and isopropyl myristate. The obtained correlations were confirmed by cluster analysis. 相似文献
169.
Todorova R 《Journal of enzyme inhibition》2001,16(4):373-380
The isomerase activity of the C-terminal fructose-6P binding domain (residues 241-608) of glucosamine-6-phosphate synthase from Escherichia coli has been studied. The equilibrium constant of the C-terminal domain k(eq) ([glucose-6P]/[fructose-6-P]) = 5.0. A non-competitive product inhibition of the isomerase activity by the reaction product glucose-6-P has been detected. The existence of more than one binding and reaction sites for the substrate fructose-6P on the molecule of glucosamine-6-phosphate synthase can be expected. The fructose-6P binding domain possibly includes a regulatory site, different from the catalytic center of the enzyme. 相似文献
170.
Nostocyclamide M: a cyanobacterial cyclic peptide with allelopathic activity from Nostoc 31 总被引:2,自引:0,他引:2
A cyclic peptide containing thiazole and oxazole moieties was isolated from Nostoc 31 and its structure determined by chemical degradation detailed NMR and mass spectroscopic analyses. The compound is stereochemically pure and closely related to nostocyclamide in which D-valine is replaced by D-methionine. Therefore, it differs from tenuecyclamide C reported to contain L-methionine. It shows allelopathic activity against Anabaena 7120, but is inactive against grazers. 相似文献