| 1. |
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| 2. |
- Adamson, L, et al.
(författare)
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Insulin and IGF-1 mediated inhibition of apoptosis in CHO cells grown in suspension in a protein-free medium
- 2007
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Ingår i: Alternatives to laboratory animals : ATLA. - : SAGE Publications. - 0261-1929 .- 2632-3559. ; 35:3, s. 349-352
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Tidskriftsartikel (refereegranskat)abstract
- When Chinese hamster ovary (CHO) cells were grown in suspension and deprived of serum, 40% of them became apoptotic after 72 hours, as determined by flow cytometry analysis of TUNEL-labelled cells. Cell viability, assessed by erythrocin B staining, decreased correspondingly. An increase in the total fraction of cells expressing interleukin converting enzyme (ICE; caspase 1), B-cell lymphoma 2 protein (Bcl-2,) and Bcl-2 associated x protein (Bax) was shown by antibody probing and subsequent flow cytometry. The p53 tumour suppressor gene product level remained low within the cell population. Insulin-like growth factor-1 (IGF-1) inhibited cell death in a concentration-dependent manner, and at 20ng/ml, cell viability was maintained close to 100% and no apoptotic cells were detected. Also, insulin was shown to inhibit cell death — at 1.0μg/ml, cell viability was 95%, whereas 10% of the cells stained for apoptosis. At the highest concentrations of IGF-1 and insulin, the expression of ICE, Bcl-2 and Bax was fully suppressed, whereas the p53 product level increased, despite still being detectable in a minority of cells. Under these conditions, IGF-1 may increase p53 expression to restrain abnormal cell proliferation. It is concluded that special attention should be paid to exposure and culture conditions that induce acquired susceptibility to a toxic insult, during the development and validation of cell-based assays.
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| 3. |
- Andres, M I, et al.
(författare)
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Polygodial-induced noradrenaline release in human neuroblastoma SH-SY5Y cells.
- 1997
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Ingår i: Toxicology in Vitro. - 0887-2333 .- 1879-3177. ; 11:5, s. 509-11
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Tidskriftsartikel (refereegranskat)abstract
- Polygodial is a natural sesquiterpene which exhibits pronounced pungency and a powerful antifeedant activity. At low concentrations, which do not alter general cell membrane permeability, polygodial increases the intracellular concentration of free calcium ([Ca(2+)](i)). Sensory neurotransmission depends on noradrenaline (NA) release, and vesicular exocytosis, in turn, is dependent on an increase in [Ca(2+)](i). The nociceptive response induced by polygodial could therefore be directly linked to intracellular calcium levels. Consequently, the objective of this work was to investigate the effect of polygodial on NA release. The human neuroblastoma cell line SH-SY5Y was selected as an in vitro model for sensory neurones. Semiconfluent cells were preloaded with tritiated NA ([(3)H]NA). After 3 min exposure of polygodial to the cells, released and unreleased radioactivity were measured. Polygodial induced a significant [(3)H]NA release at concentrations between 0.1 and 0.5 mug/ml with a maximum effect at 0.2 mug/ml (40% increased release of [(3)H]NA as compared with unstimulated control cells). No polygodial-induced transmitter release was seen at 3.5 and 5 mug/ml. For comparison, carbachol (1 rim) increased [(3)H]NA release by 10% and the KCl-induced (100 mm) [(3)H]NA release increased by 8% as compared with unstimulated SH-SY5Y cells. In conclusion polygodial, at the concentrations 0.1-0.5 mug/ml (equal to 0.4-2 mum), induces NA release which is dependent on polygodial-induced increase in [Ca(2+)](i).
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| 4. |
- Forsby, A, et al.
(författare)
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Polygodial induces inositol phosphate turnover in human neuroblastoma SH-SY5Y cells.
- 1996
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Ingår i: Neuroscience Letters. - 0304-3940 .- 1872-7972. ; 217:1, s. 50-4
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Tidskriftsartikel (refereegranskat)abstract
- The pungent sesquiterpenoid unsaturated dialdehydes polygodial and isovelleral, have previously been shown to increase the intracellular free calcium concentration [Ca2+]i in human neuroblastoma SH-SY5Y cells, partly by a release from intracellular Ca2+ stores, whereas the non-pungent compound epipolygodial, had no effect on the [Ca2+]i. In this study, we investigated the effect of isovelleral, polygodial and epipolygodial on inositol phosphate (IP) formation on the assumption that there might be a correlation between the release of intracellular Ca2+ and pungency of the compounds. It was found that polygodial induced IP mobilization in a concentration dependent way, whereas isovelleral had no effect on the IP formation in the SH-SY5Y cells. Phosphoinositide (PPI) turnover was activated by epipolygodial, but only at concentrations 40-fold higher than for polygodial, which emphasizes the importance of the correct stereometry in the dialdehyde configuration for the biological activity of polygodial. The polygodial-induced formation of IP1 was reduced by 71% under extracellular calcium-free conditions, which suggests feedback interactions between the IP formation and the increase in [Ca2+]i to account for a periodic activation of phospholipase C(PLC).
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| 5. |
- Forsby, A, et al.
(författare)
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Sesquiterpenoid unsaturated dialdehydes increase the concentration of intracellular free Ca2+ in human neuroblastoma SH-SY5Y cells.
- 1994
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Ingår i: Natural toxins (Print). - 1056-9014 .- 1522-7189. ; 2:2, s. 89-95
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Tidskriftsartikel (refereegranskat)abstract
- The effect of the three sesquiterpenoid unsaturated dialdehydes--polygodial, isovelleral, and epipolygodial--on intracellular free Ca2+ concentration, [Ca2+]i, was investigated in the human neuroblastoma cell line SH-SY5Y. [Ca2+]i was measured by the Fura-2 spectrophotofluorometric technique in multi-cell and single-cell experiments. Polygodial and isovelleral induced an increase in [Ca2+]i at low concentrations (0.1 and 0.5 micrograms/ml, respectively) but epipolygodial affected [Ca2+]i only at a high concentration (10 micrograms/ml). The results indicated that there was a relationship between the effect on [Ca2+]i and the pungency of the sesquiterpenes tested. Experiments in a Ca(2+)-free extracellular solution showed that Ca2+ was also released from intracellular calcium stores. Images from single-cell experiments indicated that polygodial induced fluctuations in the [Ca2+]i in some cells. The mechanism behind the sesquiterpene induced increase of the [Ca2+]i was not identified but a possible mobilization of inositol phosphates is considered.
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| 6. |
- Forsby, A, et al.
(författare)
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The effect of six sesquiterpenoid unsaturated dialdehydes on cell membrane permeability in human neuroblastoma SH-SY5Y cells.
- 1992
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Ingår i: Chemico-Biological Interactions. - 0009-2797 .- 1872-7786. ; 84:1, s. 85-95
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Tidskriftsartikel (refereegranskat)abstract
- The effect of six sesquiterpenes containing an unsaturated dialdehyde functionality, on cell membrane permeability in the human neuroblastoma cell line SH-SY5Y has been studied. The kinetics of the membrane leakage after addition of the sesquiterpenes were determined by measuring the efflux of radioactivity from cells preloaded with tritiated 2-deoxyglucose. The concentrations that gave 5% and 20% efflux of radioactivity as compared with control cells (EC5 and EC20) were determined for each compound. In spite of the structural similarities between the compounds, the effects on cell membrane permeability varied considerably. EC20 for polygodial, which is the most active compound, is 2.5 microM after 20-min incubation, but no leakage could be determined for merulidial even at concentrations as high as 4 mM. Rather, this compound seems to stabilize or fix the cell membrane and a lower efflux of radioactivity was observed as compared to the control cells. A quantitative structure-activity relationship analysis for the five active compounds showed a good correlation between the membrane leakage activity and certain chemical characteristics. Structural features strongly correlated with high activity were found to be: The geometry and the atomic charges of the unsaturated dialdehyde functionality, the dipole moment, the energy difference between the lowest unoccupied molecular orbital and the highest occupied molecular orbital and the lipophilicity.
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| 7. |
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| 8. |
- Magnusson, Patrik K. E., et al.
(författare)
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The Swedish Twin Registry : establishment of a biobank and other recent developments
- 2013
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Ingår i: Twin Research and Human Genetics. - Cambridge, United Kingdom : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 16:1, s. 317-329
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Tidskriftsartikel (refereegranskat)abstract
- The Swedish Twin Registry (STR) today contains more than 194,000 twins and more than 75,000 pairs have zygosity determined by an intra-pair similarity algorithm, DNA, or by being of opposite sex. Of these, approximately 20,000, 25,000, and 30,000 pairs are monozygotic, same-sex dizygotic, and opposite-sex dizygotic pairs, respectively. Since its establishment in the late 1950s, the STR has been an important epidemiological resource for the study of genetic and environmental influences on a multitude of traits, behaviors, and diseases. Following large investments in the collection of biological specimens in the past 10 years we have now established a Swedish twin biobank with DNA from 45,000 twins and blood serum from 15,000 twins, which effectively has also transformed the registry into a powerful resource for molecular studies. We here describe the main projects within which the new collections of both biological samples as well as phenotypic measures have been collected. Coverage by year of birth, zygosity determination, ethnic heterogeneity, and influences of in vitro fertilization are also described.
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| 9. |
- Molero, Y, et al.
(författare)
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A study of the possible association between adenosine A2A receptor gene polymorphisms and attention-deficit hyperactivity disorder traits.
- 2013
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Ingår i: Genes, brain, and behavior. - : Wiley. - 1601-183X .- 1601-1848. ; 12:3, s. 305-10
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Tidskriftsartikel (refereegranskat)abstract
- The adenosine A2A receptor (ADORA2A) is linked to the dopamine neurotransmitter system and is also implicated in the regulation of alertness, suggesting a potential association with attention-deficit hyperactivity disorder (ADHD) traits. Furthermore, animal studies suggest that the ADORA2A may influence ADHD-like behavior. For that reason, the ADORA2A gene emerges as a promising candidate for studying the etiology of ADHD traits. The aim of this study was to examine the relationship between ADORA2A gene polymorphisms and ADHD traits in a large population-based sample. This study was based on the Child and Adolescent Twin Study in Sweden (CATSS), and included 1747 twins. Attention-deficit hyperactivity disorder traits were assessed through parental reports, and samples of DNA were collected. Associations between six single nucleotide polymorphisms (SNPs) and ADHD traits were examined, and results suggested a nominal association between ADHD traits and three of these SNPs: rs3761422, rs5751876 and rs35320474. For one of the SNPs, rs35320474, results remained significant after correction for multiple comparisons. These results indicate the possibility that the ADORA2A gene may be involved in ADHD traits. However, more studies replicating the present results are warranted before this association can be confirmed.
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| 10. |
- Nordin-Andersson, M, et al.
(författare)
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Acrylamide-induced effects on general and neurospecific cellular functions during exposure and recovery.
- 2003
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Ingår i: Cell Biology and Toxicology. - 0742-2091 .- 1573-6822. ; 19:1, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Basal cytotoxicity, morphological changes and alterations in cell physiological and neurochemical functions were studied in differentiated human neuroblastoma (SH-SY5Y) cells during exposure to acrylamide and during a subsequent recovery period after cessation of exposure. Acrylamide induced a 20% reduction in the number of neurites per cell at 0.21 mmol/L and 20% decrease in the protein synthesis rate at 0.17 mmol/L after 72 h of exposure. Furthermore, the basal level of intracellular calcium concentration ([Ca2+]i) and receptor-activated (carbachol, 0.1 mmol/L) Ca2+ fluxes increased by 49% and 21%, respectively, at 0.25 mmol/L. These observations were made at noncytotoxic acrylamide concentrations, signifying specific neurotoxic alterations. Forty-eight hours after cessation of acrylamide exposure, the SH-SY5Y cells had recovered, i.e., the number of neurites per cell as well as the basal level of [Ca2+]i and rate of protein synthesis were comparable to those of control cells. The general calpain inhibitor calpeptin decreased the acrylamide-induced (0.5 mmol/L) neurite degeneration, determined as reduction in number of neurites per cell, from 52% to 17% as compared to control cells, which further supports the hypothesis that an increased [Ca2+]i plays a significant role for acrylamide-induced axonopathy.
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| 11. |
- Nordin-Andersson, M, et al.
(författare)
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Neurite degeneration in differentiated human neuroblastoma cells.
- 1998
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Ingår i: Toxicology in Vitro. - 0887-2333 .- 1879-3177. ; 12:5, s. 557-60
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Tidskriftsartikel (refereegranskat)abstract
- We have studied neurite degeneration in differentiated human neuroblastoma (SH-SY5Y) cells. The axonopathy-inducing potency in vitro of caffeine, diazepam, methylmercury chloride (MeHg), triethyltin chloride (TET) and acrylamide (ACR) was elucidated. After 72 hours of exposure the neurite degeneration was determined (by morphological quantification) as well as the total protein content (general cytotoxicity). The concentrations that caused 20% reduction of number of neurites (ND(20)) for ACR (250+/-36 mum) and TET (0.097+/-0.03 mum) was significantly lower, 63% and 35%, respectively (P
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| 12. |
- Skogsberg, J., et al.
(författare)
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ApoB100-LDL acts as a metabolic signal from liver to peripheral fat causing inhibition of lipolysis in adipocytes
- 2008
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Free fatty acids released from adipose tissue affect the synthesis of apolipoprotein B-containing lipoproteins and glucose metabolism in the liver. Whether there also exists a reciprocal metabolic arm affecting energy metabolism in white adipose tissue is unknown. Methods and Findings: We investigated the effects of apoB-containing lipoproteins on catecholamine-induced lipolysis in adipocytes from subcutaneous fat cells of obese but otherwise healthy men, fat pads from mice with plasma lipoproteins containing high or intermediate levels of apoB100 or no apoB100, primary cultured adipocytes, and 3T3-L1 cells. In subcutaneous fat cells, the rate of lipolysis was inversely related to plasma apoB levels. In human primary adipocytes, LDL inhibited lipolysis in a concentration-dependent fashion. In contrast, VLDL had no effect. Lipolysis was increased in fat pads from mice lacking plasma apoB100, reduced in apoB100-only mice, and intermediate in wild-type mice. Mice lacking apoB100 also had higher oxygen consumption and lipid oxidation. In 3T3-L1 cells, apoB100-containing lipoproteins inhibited lipolysis in a dose-dependent fashion, but lipoproteins containing apoB48 had no effect. ApoB100-LDL mediated inhibition of lipolysis was abolished in fat pads of mice deficient in the LDL receptor (Ldlr-/- Apob100/100). Conclusions: Our results show that the binding of apoB100-LDL to adipocytes via the LDL receptor inhibits intracellular noradrenaline-induced lipolysis in adipocytes. Thus, apoB100-LDL is a novel signaling molecule from the liver to peripheral fat deposits that may be an important link between atherogenic dyslipidemias and facets of the metabolic syndrome. © 2008 Skogsberg et al.
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| 13. |
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| 14. |
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| 15. |
- Walum, H., et al.
(författare)
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Sex Differences in Jealousy: A Population-Based Twin Study in Sweden
- 2013
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Ingår i: Twin Research and Human Genetics. - New York, USA : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 16:5, s. 941-946
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Tidskriftsartikel (refereegranskat)abstract
- According to the theory of evolved sex differences in jealousy, the challenge for women to ensure paternal investment increased their jealousy response to emotional infidelity, whereas paternal uncertainty exerted selective pressures that shaped men to become more distressed by sexual infidelity. Several studies have investigated whether the effect of these sexually dimorphic selection pressures can be detected in contemporary human populations, with conflicting results. To date, no genetically informed studies of sex differences in jealousy have been conducted. We used data from the Screening Across the Lifespan of Twins Younger (SALTY) sample, containing information concerning self-rated jealousy from 3,197 complete twin pairs collected by the Swedish Twin Registry. Intra-class correlations and structural equation models were used to assess the genetic influence on jealousy and to investigate sex differences at genetic level. We saw a highly significant sex effect on the relationship between infidelity types, indicating that men, relative to women, reported greater jealousy in response to sexual infidelity than in response to emotional infidelity. The twin models revealed significant heritabilities for both sexual (32%) and emotional (26%) jealousy. The heritabilities were of a similar magnitude in both sexes, and no qualitative sex differences could be detected. We show for the first time that variance in jealousy is to some extent explained by genetic factors. Even though our results from the mean value analyses are in line with the theory of evolved sex differences in jealousy, we could not identify any sex differences on a genetic level.
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