| 1. |
- Augustin, K, et al.
(författare)
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Green tea extracts lower serum folates in rats at very high dietary concentrations only and do not affect plasma folates in a human pilot study.
- 2009
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Ingår i: Journal of Physiology and Pharmacology. - 0867-5910 .- 1899-1505. ; 60:3, s. 103-108
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Tidskriftsartikel (refereegranskat)abstract
- Green tea catechins (GTC) have been shown to inhibit the activities of enzymes involved in folate uptake. Hence, regular green tea drinkers may be at risk of impaired folate status. The present experiments aimed at studying the impact of dietary GTC on folate concentrations and metabolism. In a human pilot study (parallel design) healthy men consumed for 3 weeks 6 capsules (approximately 670 mg GTC) per day (2 capsules with each principal meal) containing aqueous extracts of the leaves of Camellia sinensis (n=17) or placebo (n=16). No differences in plasma folate concentrations were observed between treatments. We further fed groups of 10 male rats diets fortified with 0, 0.05, 0.5, 1, or 5 g GTC/kg for 6 weeks. Only at the highest intake, GTC significantly decreased serum 5-methyl-tetrahydrofolate concentrations in rats, while mRNA concentrations of reduced folate carrier, proton-coupled folate transporter/heme carrier protein 1, and dihydrofolate reductase (DHFR) remained unchanged in intestinal mucosa. Using an in vitro enzyme activity assay, we observed a time- and dose-dependent inhibition of DHFR activity by epigallocatechin gallate and a green tea extract. Our data suggest that regular green tea consumption is unlikely to impair folate status in healthy males, despite the DHFR inhibitory activity of GTC.
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| 2. |
- Björnström, Karin, 1971-, et al.
(författare)
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Characterisation of the signal transduction cascade caused by propofol in rat neurons : From the GABAA receptor to the cytoskeleton
- 2008
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Ingår i: Journal of Physiology and Pharmacology. - 0867-5910 .- 1899-1505. ; 59:3, s. 617-632
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Tidskriftsartikel (refereegranskat)abstract
- The anaesthetic propofol interacts with the GABAA receptor, but its cellular signalling pathways are not fully understood. Propofol causes reorganisation of the actin cytoskeleton into ring structures in neurons. Is this reorganisation a specific effect of propofol as apposed to GABA, and which cellular pathways are involved? We used fluorescence-marked actin in cultured rat neurons to evaluate the percentage of actin rings caused by propofol or GABA in combination with rho, rho kinase (ROK), PI3-kinase or tyrosine kinase inhibitors, with or without the presence of extracellular calcium. Confocal microscopy was performed on propofol-stimulated cells and changes in actin between cellular compartments were studied with Western blot. Propofol (3 μg·ml-1), but not GABA (5 μM), caused transcellular actin ring formation, that was dependent on influx of extracellular calcium and blocked by rho, ROK, PI3-kinase or tyrosine kinase inhibitors. Propofol uses rho/ROK to translocate actin from the cytoskeleton to the membrane and its actin ring formation is dependent on an interaction site close to the GABA site on the GABAA receptor. GABA does not cause actin rings, implying that this is a specific effect of propofol.
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| 3. |
- Çevik Aras, Hülya, 1975, et al.
(författare)
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Melatonin-induced protein synthesis in the rat parotid gland
- 2011
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Ingår i: Journal of physiology and pharmacology. - 0867-5910. ; 62:1, s. 95-99
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Tidskriftsartikel (refereegranskat)abstract
- Melatonin occurs in large amounts in the intestinal mucosa and is released during a meal. Recent studies of ours reveal that exogenous melatonin evokes the in vivo secretion of protein and amylase from the rat parotid gland. The aim of the present study was to investigate the effect of melatonin on the protein synthesis of the parotid gland of pentobarbitone-anaesthetized rats as estimated by the rate of incorporation of [3H]leucine into trichloroacetic acid-insoluble material of the gland. Compared with the parotid protein synthesis (set at 100 %) of those rats exposed to an intravenous infusion of melatonin (25 mg/kg during 1 hour), under muscarinic and α- and β-adrenoceptor blockade, the synthesis in the corresponding glands of saline-treated control rats was less (by 25%). The synthesis was also less when the melatonin administration was combined with the melatonin 2-preffering receptor antagonist luzindole (24%), the non-selective nitric oxide synthase inhibitor L-NAME (18%) and the neuronal nitric oxide synthase inhibitor N-PLA (21%). Almost all the melatonin receptor-mediated effect was due to nitric oxide generation via the activity of neuronal type nitric oxide synthase. The present findings lend further weight to the idea that salivary glandular activity associated with food intake is hormonally influenced and they also suggest clinical implications for melatonin in the treatment of xerostomia. Since melatonin is known to exert anti-inflammatory actions in the oral cavity, the stimulatory effect of melatonin may include the synthesis of proteins of importance for the oral defence.
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| 4. |
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| 5. |
- Fedkiv, Olexandr, et al.
(författare)
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Growth is dependent on the exocrine pancreas function in young weaners but not in growing-finishing pigs
- 2009
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Ingår i: Journal of Physiology and Pharmacology. - 0867-5910. ; 60:Suppl. 3, s. 55-59
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Konferensbidrag (refereegranskat)abstract
- A correlation between the exocrine pancreatic function and growth has been previously demonstrated in growing pigs but the data are inconsistent. This was investigated by studying the growth performance of pigs with exocrine pancreatic insufficiency (EPI) at different ages and maintained under similar conditions. Twelve 7 week old (10.5 +/- 1.3 kg) weaners, and twelve 16 week old (43 +/- 5 kg) growing-finishing pigs were used in the experiments, and 6 pigs from each group were operated and pancreatic duct-ligated. Starting at 3-5 weeks after the operation, when EPI had developed, weekly recordings of feed consumption and growth were done before, during and after feed supplementation with porcine pancreatin (Creon (R) 10000). In weaner pigs, EPI caused growth arrest while it did not affect the growth of older pigs, as compared to respective un-operated groups of pigs. The daily feed consumption (DFC) was lower in the weaner EPI-pigs while it was similar in the growing-finishing EPI-pigs, as compared to un-operated pigs. Feed supplementation with Creon (R) improved the DFC and growth in both the EPI and un-operated pigs. In conclusion, the results showed the importance of the exocrine pancreatic function for growth in weaner pigs, while in older animals it played a minor role in growth. Feed supplementation with pancreatin increased the appetite and ensured an improved feed conversion.
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| 6. |
- Harrison, A. P., et al.
(författare)
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Biological effects of 2-oxoglutarate with particular emphasis on the regulation of protein, mineral and lipid absorption/metabolism, muscle performance, kidney function, bone formation and cancerogenesis, all viewed from a healthy ageing perspective state of the art - review article
- 2008
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Ingår i: JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY. - 0867-5910. ; 59, s. 91-106
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Konferensbidrag (refereegranskat)abstract
- The fact that men and women are living longer than they have ever done before is something in which we can all rejoice. However, the process of ageing is associated with changes in skeletal, muscular, gastrointestinal, neural hormonal and metabolic processes that seriously affect an individual's performance and quality of life. Indeed, Such changes can be contributory to a loss of independence in the elderly. This state-of-the art address highlights the main changes found to occur with ageing whilst simultaneously reporting findings of in vivo and in vitro studies designed to elucidate the potential of the Krebs cycle intermediate - alpha-ketoglutaric acid (AKG) in protecting elderly body systems from failing and degradation, The topics of paramount importance include impaired bone structure and strength, amino acid and mineral absorption, muscle performance, as well as highlighting the role of Krebs cycle intermediates in the debilitating changes that occur with end-stage renal failure and the regulation of the lipid metabolism. Finally, focus will be given to the role of 2-oxoglutarate as a potent protective factor in connection with the development of malignant cells in the body.
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| 7. |
- Hellmén, Eva
(författare)
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Analysis of MicroRNA Expression in Canine Mammary Cancer Stem-like Cells Indicates Epigenetic Regulation of Transforming Growth Factor-beta Signaling
- 2015
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Ingår i: Journal of Physiology and Pharmacology. - 0867-5910 .- 1899-1505. ; 66, s. 29-37
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Tidskriftsartikel (refereegranskat)abstract
- Cancer stem cells (CSCs) display both unique self-renewal ability as well as the ability to differentiate into many kinds of cancer cells. They are supposed to be responsible for cancer initiation, recurrence and drug resistance. Despite the fact that a variety of methods are currently employed in order to target CSCs, little is known about the regulation of their phenotype and biology by miRNAs. The aim of our study was to assess miRNA expression in canine mammary cancer stem-like cells (expressing stem cell antigen 1, Sca-1; CD44 and EpCAM) sorted from canine mammary tumour cell lines (CMT-U27, CMT-309 and P114). In order to prove their stem-like phenotype, we conducted a colony formation assay that confirmed their ability to form colonies from a single cell. Profiles of miRNA expression were investigated using Agilent custom-designed microarrays. The results were further validated by real-time rt-PCR analysis of expression of randomly selected miRNAs. Target genes were indicated and analysed using Kioto Encyclopedia of Genes and Genomes (KEGG) and BioCarta databases. The results revealed 24 down-regulated and nine up-regulated miRNAs in cancer stem-like cells compared to differentiated tumour cells. According to KEGG and BioCarta databases, target genes (n=240) of significantly down-regulated miRNAs were involved in transforming growth factor-beta signaling, mitogen-activated protein kinases (MAPK) signaling pathway, anaplastic lymphoma receptor tyrosine kinase (ALK) and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1A) pathways. The analysis of single-gene overlapping with different pathways showed that the most important genes were: TGFBR1, TGFBR2, SOS1, CHUK, PDGFRA, SMAD2, MEF2A, MEF2C and MEF2D. All of them are involved in tumor necrosis factor-beta signaling and may indicate its important role in cancer stem cell biology. Increased expression of TGFBR2, SMAD2, MEF2A and MEF2D in canine mammary cancer stem-like cells was further confirmed by real-time-qPCR. The results of our study point at epigenetic differences between cancer stem-like cells and differentiated tumour cells, which may be important not only for veterinary medicine but also for comparative oncology.
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| 8. |
- Hellmén, Eva
(författare)
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Transcriptomic profile of two canine mammary cancer cell lines with different proliferative and anti-apoptotic potential
- 2009
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Ingår i: Journal of Physiology and Pharmacology. - 0867-5910 .- 1899-1505. ; 60, s. 95-106
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to identify the genes responsible for the high growth rate and antiapoptotic potential in selected canine mammary cancer cells. cDNA canine microarrays were used to compare the transcriptome in simple carcinoma CMT-U27 and spindle-cell tumor CMT-U309 cell lines. In CMT- U27 cell line the growth rate (shorter cell cycle), anti-apoptotic potential (higher expression of Bcl-2) was higher and spontaneous and induced apoptosis was lower. Comparison of transcriptomes revealed 333 genes which expression differed similarly. We focused on genes involved in cell proliferation, adhesion and apoptosis, and selected 29 of them. The high growth rate and anti-apoptotic potential in CMT-U27 cells was associated with enhanced expression of genes (at the level of transcripts) involved in Ca(2+) signaling pathway (Calmodulin 1, 2, 3 and SPSB2) and growth hormone cellular pathway. The low-proliferative and pro-apoptotic phenotype of CMT-U309 cells was more dependent on TGF beta, neuregulin I pathways and adhesion-related molecules.
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| 9. |
- Hellmén, Eva
(författare)
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Tumour-associated macrophages influence canine mammary cancer stem-like cells enhancing their pro-angiogenic properties
- 2016
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Ingår i: Journal of Physiology and Pharmacology. - 0867-5910 .- 1899-1505. ; 67, s. 491-500
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Tidskriftsartikel (refereegranskat)abstract
- Cancer stem-like cells as cells with ability to self-renewal and potential to differentiate into various types of cells are known to be responsible for tumour initiation, recurrence and drug resistance. Hence a comprehensive research is concentrated on discovering cancer stem-like cells biology and interdependence between them and other cells. The aim of our study was to evaluate the impact of macrophages on cancer stem-like cells in canine mammary carcinomas. As recent studies indicated presence of macrophages in cancer environment stimulates cancer cells into more motile and invasive cells by acquisition of macrophage phenotypes. From two canine mammary tumour cell lines, CMT-U27 and P114 cancer stem-like cells were stained with Sca1, CD44 and EpCAM monoclonal antibodies and isolated. Those cells were next co-cultured with macrophages for 5 days and used for further experiments. Canine Gene Expression Microarray revealed 29 different expressed transcripts in cancer stem-like cells co-cultured with macrophages compared to those in mono-culture. Up-regulation of C-C motif chemokine 2 was considered as the most interesting for further investigation. Additionally, those cells showed overexpression of genes involved in non-canonical Wnt pathway. The results of 3D tubule formation in endothelial cells induced by cancer stem-like cells co-cultured with macrophages compared to cancer stem-like cells from mono-cultures and with addition of Recombinant Canine CCL2/MCP-1 revealed the same stimulating effect. Based on those results we can conclude that macrophages have an impact on cancer stem-like cells increasing secretion of pro-angiogenic factors.
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| 10. |
- Isola, M., et al.
(författare)
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Dynamics of the melatonin MT1 receptor in the rat parotidgland upon melatonin administration
- 2016
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Ingår i: Journal of Physiology and Pharmacology. - 0867-5910. ; 67:1, s. 111-119
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Tidskriftsartikel (refereegranskat)abstract
- Our recent ultrastructural study of human parotid glands revealed that the melatonin receptors, MT1 and MT2, are localised in the plasma cell membranes of acinar and ductal cells but also, and intriguingly, predominantly in acinar secretory granules, giving rise to the working hypothesis that secretory granules are a part of a transcytotic transport system for melatonin. To put this hypothesis to the test in rat parotid glands, anaesthetised animals were exposed to a high melatonin dose (3 mg/kg per hour), infused intravenously over two hours and aiming to stimulate a glandular melatonin-receptor-dependent intracellular transport system, if any. Thirty minutes later, the right parotids were removed. Pre-stimulation, left parotid gland tissue was removed to serve as (untreated) controls. Gland tissues were processed for the gold post-embedding technique and for western blot analysis. In untreated glands, on transmission electron microscope images, melatonin receptors displayed a distribution pattern similar to that in human parotids, i.e. here, too, the receptors were principally associated with the acinar secretory granules. In melatonin-treated glands, the number of granules associated with the MT1 receptor was twice that in untreated glands, despite the same total granule number in the two glands. Moreover, the density of gold particles showing MT1-receptor immunoreactivity associated with granules in melatonin-treated glands was 2.5 times that in untreated glands. The number of MT1 receptors associated with the granule membrane was about three times higher in melatonin-treated glands than in untreated glands, while the number of MT1 receptors inside the granules was about twice that in untreated glands. The immunoblotting of membrane-enriched samples showed that the MT1-receptor expression was about three times that of untreated glands. When it came to the MT2 receptor, no changes were observed. Melatonin itself thus exerts dynamic effects on its MT1 receptor, which may reflect an adaptive receptor-linked carrier system for melatonin, delivering - upon gland stimulation - melatonin to the saliva by exocytosis. © 2016, Polish Physiological Society. All right reserved.
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