| 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. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
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| 7. |
- Lindgren, Isa, et al.
(författare)
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Reactivity of chicken chorioallantoic arteries, avian homologue of human fetoplacental arteries
- 2010
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Ingår i: Journal of Physiology and Pharmacology. - : Polish Physiological Society. - 0867-5910 .- 1899-1505. ; 61:5, s. 619-628
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Tidskriftsartikel (refereegranskat)abstract
- The reactivity of human fetoplacental arteries is regulated by humoral and local factors of maternal and fetal origin. The chorioallantoic (CA) arteries of bird embryos are homologous to fetoplacental arteries and fulfill the same gas-exchange purpose without maternal influences, but their reactivity has not been studied in detail. In the present study we hypothesized that CA arteries would respond to vasoactive factors similarly to fetoplacental arteries and the response would change during development between maximal vascular CA expansion (15 of the 21 days incubation period) and prior to hatching. Therefore, we analyzed the reactivity of third order arteries (similar to 200 mu m) from the CA membrane of 15 and 19 day chicken embryos. CA arteries contracted in response to K+, the thromboxane A(2) mimetic U46619, endothelin-1, acetylcholine and acute hypoxia, but showed no reaction to alpha-adrenergic stimulation (phenylephrine). The nitric oxide donor sodium nitroprusside, the adenylyl cyclase agonist forskolin, and the beta-adrenergic agonist isoproterenol relaxed CA arteries precontracted with K+ or U46619. The contraction evoked by acetylcholine and the relaxations evoked by sodium nitroprusside and isoproterenol decreased with incubation age. In conclusion, CA arteries share many characteristics with human fetoplacental arteries, such as pronounced relaxation to beta-adrenergic stimuli and hypoxic vasoconstriction. Our study will be the foundation for future studies to explain disparate and common responses of the CA and fetoplacental vasculature.
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| 8. |
- Pasanen, L., et al.
(författare)
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Age-related changes in the local intestinal renin-angiotensin system in normotensive and spontaneously hypertensive rats
- 2019
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Ingår i: Journal of Physiology and Pharmacology. - : Polish Physiological Society. - 0867-5910 .- 1899-1505. ; 70:2, s. 199-208
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Tidskriftsartikel (refereegranskat)abstract
- Local renin-angiotensin systems (RAS) are found in many tissues. The main physiological effects of RAS are driven by the balance between two pathways: the angiotensin-converting enzyme I - angiotensin II receptor type 1 (ACE1-AT1R) axis and the angiotensin-converting enzyme 2 - Mas-receptor (ACE2-MAS) axis. The local intestinal RAS functions both as a paracrine regulator and as a regulator of inflammation. The expression of local RAS is known to change with age in many tissues, but age-related changes in the intestinal RAS have not been studied comprehensively. The present study characterized age-related changes in two main pathways of local RAS in the jejunum and colon of young and adult rats, in normotensive and hypertensive strains. The main finding was that 33-week-old rats exhibit an increased ratio of ACE1/ACE2 activities and protein quantity ratios compared to young rats. As the relationship of ACE1 and ACE2 mediated pathways drives the total physiological effects of RAS, the results indicate that the function of intestinal RAS changes with age. It is possible that age-related increase in ACE1-AT1R axis introduces more pro-inflammatory and fibrogenic conditions in the intestine.
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| 9. |
- Rügheimer, Louise, et al.
(författare)
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Renal Hyaluronan Content During Experimental Uncontrolled Diabetes in Rats
- 2008
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Ingår i: Journal of Physiology and Pharmacology. - 0867-5910 .- 1899-1505. ; 59:1, s. 115-128
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Tidskriftsartikel (refereegranskat)abstract
- With diabetes mellitus, the ability of the kidneys to maintain fluid balance is affected. Hyperglycaemia increases production of hyaluronan in cultured kidney cells implying that diabetes promotes induction of hyaluronan in the kidney. The aim of the present study was to determine if the interstitial matrix component hyaluronan is differently distributed within the kidney in diabetic rats compared to non-diabetic rats. Furthermore, to test if diabetic rats are able to respond with diuresis upon a hypotonic fluid load. The normal heterogeneous intrarenal distribution of hyaluronan was confirmed in non-diabetic control rats, with 60-fold more in the papilla than in the cortex. In diabetic animals, the cortical hyaluronan was unaffected but the papillary hyaluronan content was 3-fold higher than in non-diabetic rats. This increase correlated with a more than three-fold induction of the papillary hyaluronansynthase 2 mRNA expression. In non-diabetic animals, 2 h water loading increased papillary hyaluronan (+93%) and diuresis (17-fold). In diabetic animals, baseline diuresis was 8-fold higher than in non-diabetic animals, which correlated with hyperglycaemia, glucosuria and proteinuria. Water loading in diabetic animals did not further increase papillary hyaluronan or diuresis: the urine flow rate decreased. To conclude, papillary hyaluronan is elevated in diabetic rats, which coincides with induction of hyaluronan-synthase 2 mRNA, hyperglycaemia, glucosuria, proteinuria and overt diuresis. The inability to respond to a water load with further diuresis may be related to the already elevated papillary hyaluronan and the inability to change hyaluronan during water loading.
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| 10. |
- Sahlin, Kent, et al.
(författare)
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Turning down lipid oxidation during heavy exercise--what is the mechanism?
- 2008
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Ingår i: Journal of Physiology and Pharmacology. - 0867-5910 .- 1899-1505. ; 59:4, s. 19-30
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Tidskriftsartikel (refereegranskat)abstract
- A high potential for lipid oxidation is a sign of metabolic fitness and is important not only for exercise performance but also for health promotion. Despite considerable progress during recent years, our understanding of how lipid oxidation is controlled remains unclear. The rate of lipid oxidation reaches a peak at 50-60% of (V) over dotO(2) (max) after which the contribution of lipids decreases both in relative and absolute terms. In the high-intensity domain (> 60% (V) over dotO(2 max)), there is a pronounced decrease in energy state, which will stimulate the glycolytic rate in excess of the substrate requirements of mitochondrial oxidative processes. Accumulation of glycolytic products will impair lipid oxidation through an interaction with the carnitine-mediated transfer of FA into mitochondria. Another potential site of control is Acyl-CoA synthetase (ACS), which is the initial step in FA catabolism. The activity of ACS may be under control of CoASH and energy state. There is evidence that additional control points exist beyond mitochondrial influx of fatty acids. The electron transport chain (ETC) with associated feed-back control by redox state is one suggested candidate. In this review it is suggested that the control of FA oxidation during heavy exercise is distributed between ACS, CPT1, and ETC.
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