| 1. |
- Wernstedt, Ingrid, 1978, et al.
(författare)
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A common polymorphism in the interleukin-6 gene promoter is associated with overweight
- 2004
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Ingår i: Int J Obes Relat Metab Disord. ; 28:10, s. 1272-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Human body fat mass is to a large extent genetically determined, but little is known about the susceptibility genes for common obesity. Interleukin-6 (IL-6) suppresses body fat mass in rodents, and IL-6 treatment increases energy expenditure in both rodents and humans. The -174 G/C single-nucleotide polymorphism (SNP) in the IL-6 gene promoter is common in many populations, and -174 C-containing promoters have been found to be weaker enhancers of transcription. Moreover, a SNP at position -572 in the IL-6 promoter has recently been reported to affect transcription. The objective was to investigate the association between the IL-6 gene promoter SNPs and obesity. DESIGN: Trans-sectional association study of IL-6 gene promoter SNPs and indices of obesity. SUBJECTS: Two study populations, the larger one consisting of hypertensive individuals (mean age 57 y, 73% males, n=485) and the other consisting of 20 y younger nonobese healthy females (n=74). MEASUREMENTS: Genotyping for the -174 IL-6 G/C and the -572 G/C SNPs, body mass index (BMI), serum leptin levels, serum IL-6 levels, C-reactive protein, fasting blood glucose and various blood lipids. RESULTS: The common -174 C allele (f(C)=0.46), but not any -572 allele, was associated with higher BMI and higher serum leptin levels in both study populations. In the larger population, there were significant odds ratios for the association of CC (2.13) and GC (1.76) genotypes with overweight (BMI>25 kg/m(2)). Moreover, as the C allele was common, it accounted for a significant population-attributable risk of overweight (12%; CI 2-21%), although its average effect was modest in this sample. CONCLUSION: Genetically determined individual differences in production of IL-6 may be relevant for the regulation of body fat mass.
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| 2. |
- Colombani, A., et al.
(författare)
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In vitro synthesis of (1→3)-β-D-glucan (callose) and cellulose by detergent extracts of membranes from cell suspension cultures of hybrid aspen
- 2004
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Ingår i: Cellulose. - 0969-0239 .- 1572-882X. ; 11:3-4, s. 313-327
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this work was to optimize the conditions for in vitro synthesis of (1 --> 3)-beta-D-glucan (callose) and cellulose, using detergent extracts of membranes from hybrid aspen (Populus tremula x tremuloides) cells grown as suspension cultures. Callose was the only product synthesized when CHAPS extracts were used as a source of enzyme. The optimal reaction mixture for callose synthesis contained 100 mM Mops buffer pH 7.0, 1 mM UDP-glucose, 8 mM Ca2+, and 20 mM cellobiose. The use of digitonin to extract the membrane-bound proteins was required for cellulose synthesis. Yields as high as 50% of the total in vitro products were obtained when cells were harvested in the stationary phase of the growth curve, callose being the other product. The optimal mixture for cellulose synthesis consisted of 100 mM Mops buffer pH 7.0, 1 mM UDP-glucose, 1 mM Ca2+, 8 mM Mg2+, and 20 mM cellobiose. The in vitro beta-glucans were identified by hydrolysis of radioactive products, using specific enzymes. C-13-Nuclear magnetic resonance spectroscopy and transmission electron microscopy were also used for callose characterization. The (1-->3)-beta-D-glucan systematically had a microfibrillar morphology, but the size and organization of the microfibrils were affected by the nature of the detergent used for enzyme extraction. The discussion of the results is included in a short review of the field that also compares the data obtained with those available in the literature. The results presented show that the hybrid aspen is a promising model for in vitro studies on callose and cellulose synthesis.
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| 3. |
- Eriksson, Anna-Lena, 1971, et al.
(författare)
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Association between the low activity genotype of catechol-O-methyltransferase and myocardial infarction in a hypertensive population
- 2004
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Ingår i: Eur Heart J. ; 25:5, s. 386-91
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Estrogens regulate several biological processes involved in the pathogenesis of myocardial infarction. Catechol-O-methyltransferase (COMT) is a key enzyme in the degradation of estrogens. There is a functional polymorphism in the COMT gene (Val158Met), affecting the activity of the enzyme. We investigated if the low activity genotype of COMT is associated with an altered risk of myocardial infarction. METHODS AND RESULTS: In a prospectively followed hypertensive cohort we identified 174 patients who suffered a myocardial infarction during the study and compared them to 348 controls from the same cohort. The COMT polymorphism and serum levels of sex hormones were analysed. Patients homozygous for the low activity COMT genotype had a decreased risk of myocardial infarction compared to those with the high activity genotype, odds ratio 0.65 (95% CI 0.44-0.97, p=0.033 ). The protective effect of the low activity genotype was most evident among older patients (> 58 years of age), odds ratio 0.43 (95% CI 0.23-0.79, p=0.006 ). Serum levels of estradiol were increased ( p=0.006 ) in males with the low activity genotype. CONCLUSIONS: Our findings suggest that the low activity COMT genotype is protective against myocardial infarction. One may speculate that the altered estrogen status could be involved in this effect.
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| 4. |
- Lindberg, Marie K, 1975, et al.
(författare)
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Identification of estrogen-regulated genes of potential importance for the regulation of trabecular bone mineral density.
- 2002
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431. ; 17:12, s. 2183-95
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen is of importance for the regulation of trabecular bone mineral density (BMD). The aim of this study was to search for possible mechanisms of action of estrogen on bone. Ovariectomized (OVX) mice were treated with 17beta-estradiol. Possible effects of estrogen on the expression of 125 different bone-related genes in humerus were analyzed using the microarray technique. Estrogen regulated 12 of these genes, namely, two growth factor-related genes, 8 cytokines, and 2 bone matrix-related genes. Five of the 12 genes are known to be estrogen-regulated, and the remaining 7 genes are novel estrogen-regulated genes. Seven genes, including interleukin-1 receptor antagonist (IL-1ra), IL-1receptor type II (IL-1RII), insulin-like growth factor-binding protein 4 (IGFBP-4), transforming growth factor beta (TGF-beta), granulocyte colony-stimulating factor receptor (G-CSFR), leukemia inhibitory factor receptor (LIFR), and soluble IL-4 receptor (sIL-4R) were selected as probable candidate genes for the trabecular bone-sparing effect of estrogen, as the mRNA levels of these genes were highly correlated (r2 > 0.65) to the trabecular BMD. The regulation of most of these seven genes was predominantly estrogen receptor alpha (ER-alpha)-mediated (5/7) while some genes (2/7) were regulated both via ER-alpha and ER-beta. In conclusion, by using the microarray technique, we have identified four previously known and three novel estrogen-regulated genes of potential importance for the trabecular bone-sparing effect of estrogen.
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| 5. |
- Lorentzon, Mattias, 1970, et al.
(författare)
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The COMT val158met polymorphism is associated with peak BMD in men.
- 2004
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Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431. ; 19:12, s. 2005-11
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Tidskriftsartikel (refereegranskat)abstract
- The associations between the functional val158met polymorphism of the estrogen-degrading COMT enzyme and skeletal properties in young men were investigated. BMD was associated with COMT genotype. INTRODUCTION: Peak BMD is an important predictor of future risk of osteoporosis, and it is to a large extent determined by genetic factors. Estrogens are involved in the accretion of bone mass during puberty. Catechol-O-methyltransferase (COMT) is involved in the degradation of estrogens. There is a functional polymorphism in the COMT gene (val158met), resulting in a 60-75% difference in enzyme activity between the val (high activity [H]) and met (low activity [L]) variants. The aim of this cross-sectional study was to investigate the associations between this polymorphism and peak BMD in young men. MATERIALS AND METHODS: A total of 458 healthy men (mean age, 19 +/- 0.6 years) were genotyped and classified as COMT(LL), COMT(HL), or COMT(HH). Areal BMD (aBMD) was measured by DXA. Cortical and trabecular volumetric BMD (vBMD) were measured by pQCT. The associations between COMT genotype and skeletal phenotypes were determined. RESULTS AND CONCLUSIONS: Regression models using physical activity, height, weight, age, and COMT genotype as covariates showed that COMT genotype was an independent predictor of aBMD in the total body and in all femur locations investigated, but not in the spine. The values for COMT(HL) and COMT(HH) were very similar, and therefore, they were pooled into one group. aBMD at Ward's triangle, trochanter, and total femur were 4.9%, 4.5%, and 3.7% lower, respectively, in the COMT(LL) than in the COMT(HL/HH) group (p < 0.01). pQCT analyses showed that COMT genotype was an independent predictor of trabecular vBMD of the tibia, radius, and fibula. Trabecular vBMD of the radius and fibula in COMT(LL) was 5.3% and 7.4% lower, respectively, than that of the combined COMT(HL/HH) group. COMT genotype was associated with cortical vBMD but not with cortical cross-sectional area in the tibia. These findings show that the COMT polymorphism is associated with BMD in young adult men.
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| 6. |
- Movérare, Sofia, et al.
(författare)
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Differential effects on bone of estrogen receptor alpha and androgen receptor activation in orchidectomized adult male mice.
- 2003
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 100:23, s. 13573-8
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Tidskriftsartikel (refereegranskat)abstract
- Androgens may regulate the male skeleton either directly by stimulation of the androgen receptor (AR) or indirectly by aromatization of androgens into estrogens and, thereafter, by stimulation of the estrogen receptors (ERs). To directly compare the effect of ER activation on bone in vivo with the effect of AR activation, 9-month-old orchidectomized wild-type and ER-inactivated mice were treated with the nonaromatizable androgen 5alpha-dihydrotestosterone, 17beta-estradiol, or vehicle. Both ERalpha and AR but not ERbeta activation preserved the amount of trabecular bone. ERalpha activation resulted both in a preserved thickness and number of trabeculae. In contrast, AR activation exclusively preserved the number of trabeculae, whereas the thickness of the trabeculae was unaffected. Furthermore, the effects of 17beta-estradiol could not be mediated by the AR, and the effects of 5alpha-dihydrotestosterone were increased rather than decreased in ER-inactivated mice. ERalpha, but not AR or ERbeta, activation resulted in preserved thickness, volumetric density, and mechanical strength of the cortical bone. ERalpha activation increased serum levels of insulin-like growth factor I, which were positively correlated with all the cortical and trabecular bone parameters that were specifically preserved by ERalpha activation but not by AR activation, suggesting that insulin-like growth factor I might mediate these effects of ERalpha activation. Thus, the in vivo bone-sparing effect of ERalpha activation is distinct from the bone-sparing effect of AR activation in adult male mice. Because these two pathways are clearly distinct from each other, one may speculate that a combined treatment of selective ER modulators and selective AR modulators might be beneficial in the treatment of osteoporosis.
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| 7. |
- Ohlsson, Anna B., et al.
(författare)
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Gibberellic acid-induced changes in glutathione metabolism and anthocyanin content in plant tissue
- 2001
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Ingår i: Plant Cell Tissue and Organ Culture. - 0167-6857 .- 1573-5044. ; 64:1, s. 77-80
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Tidskriftsartikel (refereegranskat)abstract
- Literature data point to a possible link between gibberellic acid (GA(3)) and glutathione metabolism in plant tissue, as both are connected to dormancy breakage. In order to study the influence of GA(3) on glutathione metabolism, we treated an anthocyanin accumulating cell culture of periwinkle (Catharanthus roseus) and a shoot differentiated culture of pea (Pisum sativum) with GA(3). Glutathione reductase (GR; E.C. 1.6.4.2) activity increased to 135% and 190% of the control in C. roseus and P. sativum, respectively. The level of oxidized glutathione (GSSG) decreased to 60% of the control in the C. resells culture while no change in GSSG was observed in the P. sativum culture. No changes in the tissue concentration of total glutathione was observed in the cultures after GA(3) treatment. Concomitant. to the changes in GSSG and GR, an increase in anthocyanin accumulation was observed in the C. roseus culture in association with a strong increase in phenylalanine ammonia-lyase (PAL; E.C. 4.3.1.5) activity in response to GA(3). These data strongly suggest a link between GA(3) and glutathione metabolism.
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| 8. |
- Olanders, Knut, et al.
(författare)
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The effect of intestinal ischemia and reperfusion injury on ICAM-1 expression, endothelial barrier function, neutrophil tissue influx, and protease inhibitor levels in rats.
- 2002
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Ingår i: Shock. - 1540-0514. ; 18:1, s. 86-92
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Tidskriftsartikel (refereegranskat)abstract
- Multiple organ dysfunction syndrome (MODS) is mediated by complex mechanisms in which interactions between activated leukocytes and endothelial cells play a central role. ICAM-1 (intercellular adhesion molecule-1) mediates firm adhesion and transendothelial migration of activated leukocytes from postcapillary venules into the tissue. The present study evaluated the ICAM-1 expression in various organs after 40 min of intestinal ischemia and 1, 3, 6, 12 h of reperfusion (I/R) in the rat, using a dual monoclonal antibody technique (n = 36). Endothelial barrier permeability, using the vascular leakage of radiolabeled human serum albumin was also assessed (n = 12). Neutrophil sequestration in the lungs was quantitated by myeloperoxidase activity and plasma protease inhibitor levels were measured with electroimmunoassay. Significant regional differences were found in ICAM-1 expression between organs, both constitutively and after I/R-injury. The highest constitutive levels were observed in the liver and lungs, followed by the kidneys. The constitutive ICAM-1 expression in the intestines and in the heart was about 1/20 compared with that found in the liver and lungs. The brain and muscle had levels of about 1/150 of that in the liver and lungs. After intestinal I/R, significant increases (17-45%) were found in the lungs, intestines, brain, heart, and muscle. Albumin leakage index (ALI) in all examined organs and myeloperoxidase activity in the lungs increased after I/R-injury. Serum levels of albumin and most protease inhibitors decreased significantly after I/R challenge. Intestinal I/R results in an increase of systemic ICAM-1 expression with marked organ variability. The upregulation of ICAM-1 could represent a crucial step in the adherence- and migration process of activated leukocytes and potentially in the development of tissue injury.
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| 9. |
- Tivesten, Åsa, 1969, et al.
(författare)
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Growth hormone-induced blood pressure decrease is associated with increased mRNA levels of the vascular smooth muscle KATP channel.
- 2004
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Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 183:1, s. 195-202
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) deficiency is associated with abnormal vascular reactivity and development of atherosclerosis. GH treatment in GH deficient states restores systemic vascular resistance, arterial compliance, endothelium-dependent and endothelium-independent vasodilation, and may reverse markers of early atherosclerosis. However, very little is known about the molecular mechanisms underlying these effects. In the present study, male Sprague Dawley rats were hypophysectomized and treated for two weeks with GH (recombinant human GH, 2 mg/kg/day) or saline as s.c. injections twice daily. GH decreased aortic systolic blood pressure compared with saline-treated animals, while the diastolic blood pressure was not significantly changed. GH treatment increased cardiac output as determined by Doppler-echocardiography and the calculated systemic vascular resistance was markedly reduced. In order to identify GH-regulated genes of importance for vascular function, aortic mRNA levels were analyzed by the microarray technique and correlated to the systolic blood pressure levels. Using this approach, we identified 18 GH-regulated genes with possible impact on vascular tone and atherogenesis. In particular, mRNA levels of the inwardly rectifying potassium channel Kir6.1 and the sulfonylurea receptor 2B, which together form the vascular smooth muscle ATP-sensitive potassium channel, were both up-regulated by GH treatment and highly correlated to systolic blood pressure. Our findings establish a major role for GH in the regulation of vascular physiology and gene expression. Increased expression of the ATP-sensitive potassium channel, recently shown to be crucial in the regulation of vascular tone, constitutes a possible mechanism by which GH governs vascular tone.
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| 10. |
- Wallerstedt, Susanna Maria, 1970, et al.
(författare)
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Association analysis of the polymorphism T1128C in the signal peptide of neuropeptide Y in a Swedish hypertensive population.
- 2004
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Ingår i: Journal of hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0263-6352. ; 22:7, s. 1277-81
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The neuropeptide Y (NPY) signal peptide polymorphism T1128C has been linked to several risk factors for cardiovascular disease. The aim of the present study was to evaluate the significance of this polymorphism for cardiovascular and cerebrovascular disease outcome. DESIGN: In a prospective study cohort, 1032 hypertensive patients (174 myocardial infarction and 170 stroke patients and 688 matched controls) were analysed for the T1128C polymorphism in the NPY gene. METHODS: The dynamic allele specific hybridization (DASH) method was used for genotyping. Serum from the same participants was analysed for total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides. RESULTS: The frequency of the NPY T1128C polymorphism was 8.4% among patients with a myocardial infarction or stroke, as compared to 5.1% in the control group (P = 0.040). The difference remained significant after adjustment for the cardiovascular risk factors age, sex, smoking status, body mass index, systolic and diastolic blood pressure, presence of diabetes, total cholesterol, HDL, LDL and triglycerides. CONCLUSIONS: The present study indicates that the NPY T1128C polymorphism is an independent predictor for myocardial infarction and stroke in a Swedish hypertensive population.
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| 11. |
- Wallerstedt, Susanna Maria, 1970, et al.
(författare)
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Serum leptin and myocardial infarction in hypertension.
- 2004
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Ingår i: Blood pressure. - : Informa UK Limited. - 0803-7051 .- 1651-1999. ; 13:4, s. 243-6
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Tidskriftsartikel (refereegranskat)abstract
- The adipose tissue-derived hormone leptin is among the physiologic processes involved in cardiovascular regulation. The aim of the present study was to elucidate if serum leptin may predict cardiovascular risk, particularly myocardial infarction (MI), in hypertensive men and women. In a prospective study cohort of hypertensive men and women, serum leptin was compared in 171 patients with MI and in 342 matched controls. The mean serum concentration of leptin was 25.1 +/- 20.0 ng/ml in the MI patients and 20.0 +/- 16.6 ng/ml in the controls (p = 0.007). The association between serum leptin and MI was independent of traditional risk factors. Leptin concentrations were higher in women than in men. In women, serum leptin was the most important predictor of MI. The present study indicates that serum leptin is associated with MI in a hypertensive population. Leptin concentrations may be of practical importance when estimating the risk of MI, especially in women, where leptin was found to be the most important predictor for MI.
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