| 1. |
- Allard, Christina, et al.
(författare)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
- 2015
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Annan publikation (populärvet., debatt m.m.)abstract
- Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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| 2. |
- Alling, Christer, et al.
(författare)
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Adaptation of signal transduction in brain
- 1994
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Ingår i: EXS. - 1023-294X. ; 71, s. 19-28
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Tidskriftsartikel (refereegranskat)abstract
- Cell culture models were used to study the effects of long-term ethanol exposure on neuronal cells. Effects on phospholipase C and phospholipase D mediated signal transduction were investigated by assaying receptor-binding, G protein function, activities of lipases, formation of second messengers and c-fos mRNA. The signal transduction cascades displayed abnormal activities from 2 to 7 days of exposure which differed from the acute effects. Phosphatidylethanol formed by phospholipase D is an abnormal lipid that may harmfully affect nerve cell function.
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| 3. |
- Alling, Christer, et al.
(författare)
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Evaluation of ethanol effects on PLC signal transduction pathways using cell lines of neuronal origin
- 1993
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Ingår i: Alcohol and alcoholism. Supplement. - 1358-6173. ; 2, s. 295-299
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Tidskriftsartikel (refereegranskat)abstract
- Human neuroblastoma cells SH-SY5Y and neuroblastoma-glioma cells NG 108-15 have been used as models for the elucidation of the effects of ethanol on receptor-mediated phospholipase C activity, c-fos mRNA expression and protein kinase C activity. Cells were exposed to ethanol (0-200 mM) for varying periods up to seven days. Agonist stimulated events were obtained in NG 108-15 cells with bradykinin and in SH-SY5Y cells with carbachol. Chronic ethanol exposure reduced the agonist-stimulated formation of inositol 1,4,5-trisphosphate in NG 108-15 cells and in SH-SY5Y cells. 100 mM ethanol for seven days increased the membrane bound and cytosolic forms of protein kinase C activity in SH-SY5Y cells. Carbachol (1 mM) induced a maximal c-fos mRNA response after 40 minutes in SH-SY5Y cells, an effect that could be mimicked through protein kinase C stimulation by phorbol esters.
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| 4. |
- Alling, Christer, et al.
(författare)
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Muscarinic receptor-stimulated expression of c-fos in neuroblastoma cells
- 1994
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Ingår i: Alcohol and alcoholism. Supplement. - 1358-6173. ; :2, s. 103-108
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Tidskriftsartikel (refereegranskat)abstract
- The intracellular signal cascade transducing muscarinic-receptor-stimulation to gene expression was investigated in human neuroblastoma SH-SY5Y cells. Naive and ethanol-exposed SH-SU5Y cells were stimulated with carbachol (CCh) and inositol 1,4-5-trisphosphate (IP3), 1,2-diacylglycerol (DAG), and c-fos mRNA levels were analyzed using a radioreceptor assay (IP3) thin-layer chromatography (DAG) and Northern blot (c-fos mRNA). Application of the muscarinic agonist CCh induced a rapid increase in (IP3), peaking within seconds after the CCh-addition. There was also an accumulation of DAG reaching maximum after 5 min of receptor-stimulation. Stimulation with CCh also induced expression of the immediate-early gene c-fos in these cells. These events were mediated via muscarinic M1 receptors and the inhibitory effects of H7, staurosporin, and RO31-7549 on the c-fos expression indicated that it was mediated via protein kinase C. Acute exposure to 100 mM ethanol inhibited the formation of IP3 and the expression of c-fos. These effects were due to an increase in the EC50 of CCh for the events. Exposure to 100 mM ethanol for 4 days caused a potentiation of these two events. The EC50 was unaffected but the maximal response was increased. These data indicate that this signal transduction system is inhibited by acute exposure to 100 mM ethanol, an effect that is compensated for after exposure to ethanol for 4 days.
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| 5. |
- Alsterfjord, Magnus, et al.
(författare)
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Plasma membrane H+-ATPase and 14-3-3 Isoforms of Arabidopsis leaves: Evidence for isoform specificity in the 14-3-3/H+-ATPase interaction
- 2004
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Ingår i: Plant and Cell Physiology. - : Oxford University Press (OUP). - 1471-9053 .- 0032-0781. ; 45:9, s. 1202-1210
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Tidskriftsartikel (refereegranskat)abstract
- The plasma membrane H+-ATPase is activated by binding of 14-3-3 protein to the phosphorylated C terminus. Considering the large number of 14-3-3 and H+-ATPase isoforms in Arabidopsis (13 and 11 expressed genes, respectively), specificity in binding may exist between 14-3-3 and H+-ATPase isoforms. We now show that the H'-ATPase is the main target for 14-3-3 binding at the plasma membrane, and that all twelve 14-3-3 istiforms tested bind to the H+-ATPase in vitro. Using specific antibodies for nine of the 14-3-3 isoforms, we show that GF14epsilon, mu, lambda, omega, chi, phi, nu, and upsilon are present in leaves, but that isolated plasma membranes lack GF14chi, phi and upsilon. Northern blots using isoform-specific probes for all 14-3-3 and H+-ATPase isoforms showed that transcripts were present for most of the isoforms. Based on mRNA levels, GF14epsilon, mu, lambda and chi are highly expressed 14-3-3 isoforms, and AHA1, 3, and 11 highly expressed H+-ATPase isoforms in leaves. However, mass peptide fingerprinting identified AHA1 and 2 with the highest score, and their presence could be confirmed by MS/MS. It may be calculated that under 'unstressed' conditions less than one percent of total 14-3-3 is attached to the H+-ATPase. However, during a condition requiring full activation of H+ pumping, as induced here by the presence of the fungal toxin fusicoccin, several percent of total 14-3-3 may be engaged in activation of the H+-ATPase.
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| 6. |
- Bernfur, Katja, et al.
(författare)
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Relative abundance of integral plasma membrane proteins in Arabidopsis leaf and root tissue determined by metabolic labeling and mass spectrometry.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic labeling of proteins with a stable isotope ((15)N) in intact Arabidopsis plants was used for accurate determination by mass spectrometry of differences in protein abundance between plasma membranes isolated from leaves and roots. In total, 703 proteins were identified, of which 188 were predicted to be integral membrane proteins. Major classes were transporters, receptors, proteins involved in membrane trafficking and cell wall-related proteins. Forty-one of the integral proteins, including nine of the 13 isoforms of the PIP (plasma membrane intrinsic protein) aquaporin subfamily, could be identified by peptides unique to these proteins, which made it possible to determine their relative abundance in leaf and root tissue. In addition, peptides shared between isoforms gave information on the proportions of these isoforms. A comparison between our data for protein levels and corresponding data for mRNA levels in the widely used database Genevestigator showed an agreement for only about two thirds of the proteins. By contrast, localization data available in the literature for 21 of the 41 proteins show a much better agreement with our data, in particular data based on immunostaining of proteins and GUS-staining of promoter activity. Thus, although mRNA levels may provide a useful approximation for protein levels, detection and quantification of isoform-specific peptides by proteomics should generate the most reliable data for the proteome.
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| 7. |
- Ding, W Q, et al.
(författare)
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Acute ethanol exposure attenuates expression of junD in human neuroblastoma cells
- 1998
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Ingår i: Neurochemistry International. - 0197-0186. ; 33:6, s. 525-530
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Tidskriftsartikel (refereegranskat)abstract
- This study describes the effects of acute ethanol exposure on the mRNA levels of c-jun,junB and junD in the human neuroblastoma SH-SY5Y cell line. An acute exposure to 100 mM ethanol did not influence the basal and phorbol ester-induced expression of c-jun and junB, whereas the basal mRNA level of junD was attenuated by 30%. This effect was dose- and time-dependent with maximal inhibition being detected 2 h after 100 mM ethanol treatment and the mRNA levels gradually returned towards normal afterwards. Ethanol also inhibited phorbol ester-induced expression of junD. The fact that ethanol did not influence degradation of the junD mRNA suggests that acute ethanol suppresses the transcription of the gene. These results indicate that acute ethanol exerts different effects on expression of Jun transcription factors, suggesting that as compared to c-jun and junB, the junD gene may be more sensitive to acute ethanol treatment in neuronal cells.
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| 8. |
- Ding, W Q, et al.
(författare)
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Effects of ethanol on muscarinic receptor-stimulated c-fos expression in human neuroblastoma cells
- 1997
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Ingår i: Brain Research. Molecular Brain Research. - 0169-328X. ; 46:1-2, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- The effect of ethanol exposure on muscarinic receptor-stimulated expression of c-fos was investigated in SH-SY5Y cells. Four days of ethanol exposure enhanced carbachol-stimulated c-fos mRNA expression, analyzed with Northern blot, and Fos/AP-1 binding activity, measured with gel mobility super shift assay. Pre-incubation with muscarinic antagonists or the protein kinase C inhibitor GF109203X demonstrated that, in both control and ethanol-treated cells, carbachol-induced c-fos expression was mediated via muscarinic M1 receptors and to a large extent through protein kinase C. However, phorbol ester-induced c-fos expression was unaffected in ethanol-treated cells. Acute exposure to ethanol caused a suppression of both carbachol- and phorbol ester-stimulated c-fos expression. These results demonstrate that muscarinic receptor-stimulated gene expression is sensitive to both acute and long-term ethanol exposure.
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| 9. |
- Ding, Wei-Qun, et al.
(författare)
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Ethanol exposure increases expression of c-jun and junD in human neuroblastoma cells
- 1996
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Ingår i: NeuroReport. - 1473-558X. ; 7:13, s. 2191-2195
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the effect of ethanol exposure on the expression of fos and jun genes. Exposure of human neuroblastoma SH-SY5Y cells to ethanol for 2-4 days caused a dose-dependent increase in c-jun and junD mRNA levels, whereas mRNAs for c-fos, fosB and junB were not detectable in control or ethanol-treated cells. Four days of ethanol exposure also enhanced the AP-1 binding activity. Experiments with actinomycin D demonstrated that ethanol did not influence the degradation of c-jun and junD mRNAs. These results demonstrate that long-term exposure to ethanol increases c-jun and junD expression. This effect may be one of the mechanisms through which ethanol influences the gene regulatory system in neuronal cells.
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| 10. |
- Ding, Wei-Qun, et al.
(författare)
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Ethanol exposure potentiates fosB and junB expression induced by muscarinic receptor stimulation in neuroblastoma SH-SY5Y cells
- 1998
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Ingår i: Alcoholism: Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 22:1, s. 225-230
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Tidskriftsartikel (refereegranskat)abstract
- Muscarinic receptor stimulation and activation of protein kinase C cause an increase in fosB and junB transcripts in human neuroblastoma SH-SY5Y cells. In this study, the effect of long-term ethanol exposure on these events was investigated. Carbachol-stimulated fosB and junB expression was elevated in ethanol-exposed cells compared with control cells. The potentiation was time- and dose-dependent on ethanol. Preincubation with muscarinic antagonists or protein kinase C inhibitor demonstrated that the carbachol-stimulated increase in fosB and junB mRNA levels was primarily mediated via M1 receptors and dependent on the activity of protein kinase C in both control and ethanol-exposed cells. Long-term ethanol exposure did not influence the expression of fosB and junB induced by activation of protein kinase C with phorbol ester. These results demonstrate that the muscarinic receptor-stimulated fosB and junB expression is sensitive to ethanol exposure in SH-SY5Y cells, suggesting that these genes participate in the regulation of neuronal function in response to chronic ethanol treatment.
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| 11. |
- Ding, Wei-Qun, et al.
(författare)
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Stimulation of muscarinic receptors induces expression of individual fos and jun genes through different transduction pathways
- 1998
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Ingår i: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 70:4, s. 1722-1729
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Tidskriftsartikel (refereegranskat)abstract
- The transduction pathways coupling muscarinic receptors to induction of fos and jun genes were investigated in neuroblastoma SH-SY5Y cells. Stimulation with carbachol induced expression of c-fos, fosB, c-jun, junB, and junD. This effect was abolished by pretreatment with atropine, indicating an involvement of muscarinic receptors. These genes were also induced by activation of protein kinase C with phorbol ester or by elevating the intracellular Ca2+ concentration with a Ca2+ ionophore. The Ca2+ effect was inhibited by KN-62, suggesting an induction through Ca2+/calmodulin-dependent kinase II. Inhibition of protein kinase C with GF109203X suppressed the carbachol-stimulated increase in mRNA levels of c-fos, fosB, and junB by approximately 70% but had only minor effects on the expression of c-jun and junD. On the other hand, preincubation with KN-62 attenuated the carbachol-induced increase in c-jun and junD expression by 70% but had no effect on c-fos, fosB, and junB mRNA levels. Simultaneous inhibition of both protein kinase C and Ca2+/calmodulin-dependent kinase II completely abolished the carbachol-stimulated expression of c-jun and junD, but c-fos, fosB, and junB were still expressed to a certain extent under this condition. Comparison of the inhibitory effects of GF109203X and Go 6976 suggests the involvement of classical protein kinase C isozymes in muscarinic receptor-stimulated expression of fos and jun genes. These results demonstrate that the muscarinic receptor-induced expression of individual fos and jun genes is regulated via different pathways, primarily protein kinase C or Ca2+/calmodulin-dependent kinase II.
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| 12. |
- Elbir, Haitham, et al.
(författare)
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Genome Sequence of the Asiatic Species Borrelia persica
- 2014
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Ingår i: Genome Announcements. - 2169-8287. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the complete genome sequence of Borrelia persica, the causative agent of tick-borne relapsing fever borreliosis on the Asian continent. Its genome of 1,784,979 bp contains 1,850 open reading frames, three ribosomal RNAs, and 32 tRNAs. One clustered regularly interspaced short palindromic repeat (CRISPR) was detected.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Janson, Christer, et al.
(författare)
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Scientific rationale for the possible inhaled corticosteroid intraclass difference in the risk of pneumonia in COPD
- 2017
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Ingår i: The International Journal of Chronic Obstructive Pulmonary Disease. - 1176-9106 .- 1178-2005. ; 12, s. 3055-3064
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Forskningsöversikt (refereegranskat)abstract
- Inhaled corticosteroids (ICSs) treatment combined with long-acting β2-adrenoceptor agonists (LABAs) reduces the risk of exacerbations in COPD, but the use of ICSs is associated with increased incidence of pneumonia. There are indications that this association is stronger for fluticasone propionate than for budesonide. We have examined systematic reviews assessing the risk of pneumonia associated with fluticasone propionate and budesonide COPD therapy. Compared with placebo or LABAs, we found that fluticasone propionate was associated with 43%–78% increased risk of pneumonia, while only slightly increased risk or no risk was found for budesonide. We have evaluated conceivable mechanisms which may explain this difference and suggest that the higher pneumonia risk with fluticasone propionate treatment is caused by greater and more protracted immunosuppressive effects locally in the airways/lungs. These effects are due to the much slower dissolution of fluticasone propionate particles in airway luminal fluid, resulting in a slower uptake into the airway tissue and a much longer presence of fluticasone propionate in airway epithelial lining fluid.
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| 17. |
- Jonsdottir, Berglind, et al.
(författare)
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Childhood thyroid autoimmunity and relation to islet autoantibodies in children at risk for type 1 diabetes in the diabetes prediction in skåne (DiPiS) study
- 2018
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Ingår i: Autoimmunity. - : Informa UK Limited. - 0891-6934 .- 1607-842X. ; 51:5, s. 228-237
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim was to determine prevalence and age at seroconversion of thyroid autoimmunity in relation to islet autoantibodies, gender and HLA-DQ genotypes in children with increased risk for type 1 diabetes followed from birth. Methods: In 10-year-old children (n = 1874), blood samples were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase 65 (GADA), Zink transporter 8 (ZnT8R/W/QA), insulinoma-associated protein-2 (IA-2A), insulin (IAA) and HLA-DQ genotypes. Prospectively collected samples from 2 years of age were next analysed for TPOAb, and TGAb and, finally, in confirming samples at 11–16 years of age along with TSH and FT4. Frequencies were tested with Chi-square or Fischer’s exact tests, autoantibody levels with Wilcoxon and correlations between autoantibody levels with Spearman’s rank correlation test. Results: The prevalence of thyroid autoimmunity was 6.9%, overrepresented in girls (p <.001) also having higher TPOAb levels at 10 years (p =.049). TPOAb was associated with GADA (p =.002), ZnT8R/W/QA (p =.001) and IA-2A (p =.001) while TGAb were associated with ZnT8R/W/QA (p =.021). In boys only, TPOAb were associated with GADA (p =.002), IA-2A (p =.001), ZnT8R/W/QA (p =.001) and IAA (p =.009), and TGAb with GADA (p =.013), IA-2A (p =.005) and ZnT8R/W/QA (p =.003). Levels of IA-2A correlated to both TPOAb (p =.021) and to TGAb (p =.011). In boys only, levels of GADA and TGAb correlated (p =.009 as did levels of IA-2A and TPOAb (p =.013). The frequency and levels of thyroid autoantibodies increased with age. At follow-up, 22.3% had abnormal thyroid function or were treated with thyroxine. Conclusions: Thyroid autoimmunity and high TPOAb levels were more common in girls. In contrast, in boys only, there was a strong association with as well as correlation between levels of thyroid and islet autoantibodies. It is concluded that while girls may develop autoimmune thyroid disease (AITD) independent of islet autoantibodies, the risk for thyroid disease in boys may be linked to concomitant islet autoimmunity.
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| 18. |
- Jonsdottir, Berglind, et al.
(författare)
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Thyroid and islet autoantibodies predict autoimmune thyroid disease already at Type 1 diabetes diagnosis
- 2017
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 102:4, s. 1277-1285
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Screening of autoimmune thyroid disease in children and young adults with Type 1 diabetes is important but vary greatly between clinics.OBJECTIVE: The aim was to determine the predictive value of thyroid autoantibodies, thyroid function, islet autoantibodies, and HLA- DQ at diagnosis of Type 1 diabetes for autoimmune thyroid disease during subsequent follow-up.SETTING: 43 Paediatric Endocrinology units Sweden. Design, patients and main outcome measures: At diagnosis of Type 1 diabetes, samples from 2433 children were analysed for autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TGAb), glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated protein-2 (IA-2A), and the three variants of the zinc transporter 8 (ZnT8W/R/QA) as well as HLA-DQA1-B1 genotypes and thyroid function. After 5.1-9.5 years disease duration, children treated with thyroxine were identified in the Swedish National Board of Health and Welfare Prescribed Drug Register.RESULTS: Thyroxine had been prescribed to 6% (147/2433; 66% girls). In patients below 5 years, female gender (HR=4.60, p=0.008) and GADA (HR=5.80, p=0.02) were significant predictors. In patients 5-10 years, TPOAb (HR=20.56, p<0.0001), TGAb (HR=3.40, p=0.006) and TSH outside the reference limit (HR=3.64, p<0.001) were predictors while in the 10-15 year olds, TPOAb (HR=17.00, p<0.001) and TSH outside the reference limit (HR=4.11, p<0.001) predicted future thyroxine prescription.CONCLUSION: In addition to TPOAb and TSH, positive GADA tested at the diagnosis of type 1 diabetes is important for the prediction of autoimmune thyroid disease in children below 5 years of age.
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| 19. |
- Larsson, Christer, et al.
(författare)
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An okadaic acid-sensitive protein phosphatase counteracts protein kinase C-induced phosphorylation in SH-SY5Y cells
- 1993
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Ingår i: Cellular Signalling. - 1873-3913. ; 5:3, s. 305-313
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Tidskriftsartikel (refereegranskat)abstract
- Protein phosphorylation and subsequent dephosphorylation was studied in digitonin-permeabilized neuroblastoma SH-SY5Y cells by measuring the incorporation of [32P]phosphate into myelin basic protein (MBP). 1,2-Dioctanoyl-sn-glycerol (DOG) and calcium synergistically induced phosphorylation of MBP, which was inhibited by the protein kinase C (PKC) pseudosubstrate peptide (PKC19-36). The phosphorylation increased for 10 min when a net dephosphorylation started to appear. The dephosphorylation was inhibited by okadaic acid. Regardless of calcium concentration, the presence of DOG was necessary for significant effects of okadaic acid on MBP phosphorylation. H7 and staurosporine dose-dependently inhibited the phosphorylation of MBP, induced by DOG and calcium in the presence of okadaic acid. Different PKC pseudosubstrate peptides were applied and all showed an inhibitory effect on the phosphorylation of MBP under these conditions. These results demonstrate the presence, in SH-SY5Y cells, of a protein phosphatase, possibly protein phosphatase 2A, with a high basal activity that counteracts PKC-induced phosphorylation.
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| 20. |
- Larsson, Christer, et al.
(författare)
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Calmidazolium inhibits muscarinic receptor-mediated PLC activation in SH-SY5Y cells
- 1995
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Ingår i: NeuroReport. - 1473-558X. ; 6:9, s. 1333-1337
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the effect of a calmodulin antagonist, calmidazolium, on the muscarinic receptor-mediated increase in inositol 1,4,5-trisphosphate [I(1,4,5)P3] in SH-SY5Y cells. Exposure to 10 microM calmidazolium suppressed the initial I(1,4,5)P3 peak increase (IC50 1 microM) whereas the steady-state was less affected. Furthermore, calmidazolium displayed non-competitive antagonistic properties of [3H]quinuclidinyl benzylate binding to intact SH-SY5Y cells and to membranes from these cells. These effects were also obtained with another calmodulin inhibitor, trifluoperazine (10 microM). These results demonstrate that novel finding that the calmodulin inhibitors calmidazolium and trifluoperazine act as non-competitive muscarinic antagonists in SH-SY5Y cells and inhibit muscarinic receptor-stimulated phospholipase C activation in these cells.
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| 21. |
- Larsson, Christer, et al.
(författare)
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Ethanol inhibits the peak of muscarinic receptor-stimulated formation of inositol 1,4,5-trisphosphate in neuroblastoma SH-SY5Y cells
- 1995
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Ingår i: Biochemical Pharmacology. - : Elsevier BV. - 0006-2952. ; 50:5, s. 647-654
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Tidskriftsartikel (refereegranskat)abstract
- The effect of ethanol on muscarinic receptor-stimulated formation of inositol 1,4,5-trisphosphate was studied in human neuroblastoma SH-SY5Y cells. Stimulation with carbachol induced a biphasic increase of inositol 1,4,5-triphosphate with an initial peak after 10 sec declining to a plateau phase of elevation above basal levels, which was sustained for at least 5 min in the presence of agonist. The peak, but not the plateau phase, was concentration-dependently decreased by exposure to ethanol. Maximal inhibition was obtained within 30 sec of exposure to ethanol. Ethanol caused an increase in the EC50 value of carbachol for the initial rate of inositol 1,4,5-trisphosphate formation, measured after 10 sec of stimulation, from 98 microM in the absence to 196 microM in the presence of 100 mM ethanol. The potencies of pirenzepine and hexahydro-sila-difenidol hydrochloride for inhibiting [3H]quinuclidinyl benzilate binding and inositol 1,4,5-trisphosphate formation suggest that both phases are mediated via the muscarinic M1 receptor. Phorbol 12-myristate 13-acetate inhibited both phases of inositol 1,4,5-trisphosphate formation, whereas okadaic acid and modulators of cAMP-dependent protein kinase were without any effect. There was no inhibitory effect of ethanol when protein kinase C was inhibited by H7 and calphostin C, indicating that the ethanol effect is dependent on protein kinase C activity.
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| 22. |
- Larsson, Christer, et al.
(författare)
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Long-term exposure to ethanol increases the number and function of muscarinic M1 receptors in human neuroblastoma cells
- 1996
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - 1521-0103. ; 278:1, s. 313-319
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Tidskriftsartikel (refereegranskat)abstract
- The effect of long-term ethanol exposure on muscarinic receptors was investigated in human neuroblastoma SH-SY5Y cells. Exposure to 100 mM ethanol for 4 days enhanced both peak and steady-state levels of carbachol-stimulated inositol 1,4,5-bisphosphate increase. An ethanol concentration of 50 mM was sufficient for an enhancement of this event. The carbachol-stimulated decrease in [3H]inositol-labeled [3H]phosphatidylnositol 4,5-bisphosphate and increase [3H]inositol trisphosphate and [3H]inositol bisphosphate were also potentiated in ethanol-treated cells, which demonstrated that the receptor-stimulated activation of phospholipase C is augmented. Experiments with pirenzepine showed that carbachol-stimulated inositol 1,4,5-trisphosphate increase is mediated via M1 receptors both in ethanol-treated and control cells. Ethanol exposure for 2 or 4 days also caused an increase in [3H]N-methylscopolamine and [3H]quinuclidinyl benzilate binding sites and elevation of [3H]pirenzepine binding, which indicated that the number of muscarinic M1 receptors is increased in ethanol-treated SH-SY5Y cells. These results demonstrate that long-term exposure to ethanol potentiates muscarinic M1 receptor-stimulated activation of phospholipase C in SH-SY5Y cells. This is likely to be explained by an increased number of muscarinic M1 receptors.
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| 23. |
- Larsson, Christer, et al.
(författare)
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Mechanisms of muscarinic receptor-stimulated expression of c-fos in SH-SY5Y cells
- 1994
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Ingår i: European Journal of Pharmacology. - 1879-0712. ; 268:1, s. 19-28
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the signal cascade transducing carbachol stimulation into c-fos expression in SH-SY5Y neuroblastoma cells was investigated. 1,2-Diacylglycerol formation and c-fos expression were mediated via stimulation of muscarinic M1 receptors and the first 5 min of receptor stimulation were critical for these events. Application of 1,2-dioctanoylglycerol induced c-fos expression and this, as well as carbachol-stimulated c-fos expression, was inhibited by protein kinase C inhibitors. Increasing the intracellular Ca2+ concentration had only small effects on c-fos expression. There was a dependency on extracellular Ca2+ for maximal c-fos expression and 1,2-diacylglycerol formation. The carbachol-stimulated c-fos expression was potentiated by application of the protein phosphatase inhibitor okadaic acid. These results demonstrate the importance of 1,2-diacylglycerol formation for muscarinic receptor-stimulated, protein kinase C-mediated c-fos expression in the SH-SY5Y cells and that this cascade is counteracted by an okadaic acid-sensitive protein phosphatase.
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| 24. |
- Larsson, Helena, et al.
(författare)
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Baseline heterogeneity in glucose metabolism marks the risk for type 1 diabetes and complicates secondary prevention.
- 2015
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 1432-5233 .- 0940-5429. ; 52:3, s. 473-481
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Tidskriftsartikel (refereegranskat)abstract
- Non-diabetic children with multiple islet autoantibodies were recruited to a secondary prevention trial. The objective was to determine the predictive value of baseline (1) HbA1c and metabolic variables derived from intravenous (IvGTT) and oral glucose tolerance tests (OGTT), (2) insulin resistance and (3) number, type and levels of islet autoantibodies, for progression to type 1 diabetes.
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| 25. |
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