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Dietary haem stimulates epithelial cell turnover by downregulating feedback inhibitors of proliferation in murine colon
IJssennagger, N. ; Rijnierse, A. ; Wit, N. de; Jonker-Termont, D.S.M.L. ; Dekker, J. ; Muller, M.R. ; Meer, R. van der - \ 2012
Gut 61 (2012)7. - ISSN 0017-5749 - p. 1041 - 1049.
colorectal-cancer - red meat - rat colon - factor-i - differentiation - mechanisms - risk - consumption - apoptosis - cohort
Objective Colon cancer is a leading cause of cancer deaths in Western countries and is associated with diets high in red meat. Haem, the iron-porphyrin pigment of red meat, induces cytotoxicity of gut contents and damages the colon surface epithelium. Compensatory hyperproliferation leads to epithelial hyperplasia which increases the risk of colon cancer. The aim of this study was to identify molecules signalling from the surface epithelium to the crypt to initiate hyperproliferation upon stress induced by haem. Methods C57Bl6/J mice (n=9/group) received a ‘westernised’ control diet (40 en% fat) with or without 0.5 µmol/g haem for 14 days. Colon mucosa was used to quantify cell proliferation and for microarray transcriptome analysis. Gene expression profiles of surface and crypt cells were compared using laser capture microdissection. Protein levels of potential signalling molecules were quantified. Results Haem-fed mice showed epithelial hyperproliferation and decreased apoptosis, resulting in hyperplasia. Microarray analysis of the colon mucosa showed 3710 differentially expressed genes (false discovery rate (q)
Multiplex ready flow cytometric immunoassay for total insulin like growth factor 1 in serum of cattle
Bremer, M.G.E.G. ; Smits, N.G.E. ; Haasnoot, W. ; Nielen, M.W.F. - \ 2010
The Analyst 135 (2010). - ISSN 0003-2654 - p. 1147 - 1152.
exogenous bovine somatotropin - factor-i - binding-proteins - lactating cows - hormone - validation
The European Union has banned the use of recombinant bovine somatotropins (rbST, growth hormones) to increase milk yield in dairy cattle. As direct detection of rbST in serum is problematic, methods based on the detection of changes in multiple rbST-dependent biomarkers have high potential for monitoring rbST abuse. In this study immunoassays were developed for total insulin-like growth factor 1 (IGF-1) in cow sera. Ultimately aiming at combination with other rbST-dependent biomarker assays two multiplex formats were studied and compared critically, a multi-channel surface plasmon resonance (SPR)-based biosensor and flow cytometry combined with color encoded microbeads. Moreover, a new dedicated sample pretreatment was developed for the dissociation of complexed IGF-1 in serum, while keeping other biomarkers in solution. Compared to the SPR biosensor immunoassay, the flow cytometric immunoassay (FCIA) was more sensitive, less antibody-consuming and less vulnerable to necessary but interfering reagents from the sample treatment. In an initial in-house validation study the developed FCIA showed to be fast, specific, robust, and a high repeatability and reliability, and generated realistic IGF-1 values for bovine serum, without compromising the potential for simultaneous detection of other biomarkers. Due to the xMAP technology, in which 100 different bead sets can be measured simultaneously, the total IGF-1 assay can easily be extended with other immunoassays for candidate biomarkers. Preliminary results about a FCIA for IGF-1 multiplexing with insulin-like growth factor binding protein 2 (IGFBP2) are presented which strongly supported both the FCIA multiplex format as well as the generic nature of the developed sample pretreatment.
Targeted and untargeted profiling of biological fluids to screen for anabolic practices in cattle
Pinel, G. ; Weigel, S. ; Antigac, P. ; Mooney, M.H. ; Elliott, C. ; Nielen, M.W.F. ; Bizec, B. le - \ 2010
TrAC : Trends in Analytical Chemistry 29 (2010)11. - ISSN 0165-9936 - p. 1269 - 1280.
flight mass-spectrometry - human growth-hormone - gene-expression-biomarkers - veal calves - liquid-chromatography - human urine - doping control - factor-i - promoting purposes - steroids
This review deals with the potential of profiling approaches as valuable tools for combating the illegal use of growth promoters in cattle breeding. Detection of illegal practices classically relies on residue monitoring in a targeted approach and methods based on gas or liquid chromatography coupled to (tandem) mass spectrometry are considered state of the art. However, these strategies fail when faced with new xenobiotic growth-promoting agents or new ways of application, such as administration of low-dose cocktails. In this context, screening strategies allowing detection of the physiological response resulting from administration of anabolic compounds are promising approaches to detect misuse. Profiling biological matrices to reveal biological effects of a drug can be performed by targeting a particular class of compounds or in an untargeted way using global strategies, such as transcriptomics, proteomics or metabolomics. These emerging tactics are promising ways to highlight candidate biomarkers to tackle illegal practices.
Role of multiprotein bridging factor 1 in archaea: bridging the domains?
Koning, B. de; Blombach, F. ; Wu Hao, ; Brouns, S.J.J. ; Oost, J. van der - \ 2009
Biochemical Society Transactions 37 (2009)1. - ISSN 0300-5127 - p. 52 - 57.
transcriptional coactivator mbf1 - box-binding-protein - p-loop gtpases - factor-i - saccharomyces-cerevisiae - secondary structure - oxidative stress - gene-expression - bombyx-mori - arabidopsis
MBF1 (multiprotein bridging factor 1) is a highly conserved protein in archaea and eukaryotes. It was originally identified as a mediator of the eukaryotic transcription regulator BmFTZ-F1 (Bombyx mori regulator of fushi tarazu). MBF1 was demonstrated to enhance transcription by forming a bridge between distinct regulatory DNA-binding proteins and the TATA-box-binding protein. MBF1 consists of two parts: a C-terminal part that contains a highly conserved helix-turn-helix, and an N-terminal part that shows a clear divergence: in eukaryotes, it is a weakly conserved flexible domain, whereas, in archaea, it is a conserved zinc-ribbon domain. Although its function in archaea remains elusive, its function as a transcriptional co-activator has been deduced from thorough studies of several eukaryotic proteins, often indicating a role in stress response. In addition, MBF1 was found to influence translation fidelity in yeast. Genome context analysis of mbf1 in archaea revealed conserved clustering in the crenarchaeal branch together with genes generally involved in gene expression. It points to a role of MBF1 in transcription and/or translation. Experimental data are required to allow comparison of the archaeal MBF1 with its eukaryotic counterpart
Inhibition of methylation and changes in gene expression in relation to neural tube defects
Linden, I.J. van der; Heil, S.G. ; Egmont-Petersen, M. van; Straaten, H.W. ; Heijer, M. den - \ 2008
Birth defects research. Part A, Clinical and molecular teratology 82 (2008)10. - ISSN 1542-0752 - p. 676 - 683.
factor-i - methylenetetrahydrofolate reductase - serine/threonine kinase - caenorhabditis-elegans - mammalian development - common mutation - risk-factor - dna - serine - folate
BACKGROUND: An impaired DNA methylation has been suggested to underlie the complex etiology of neural tube defects (NTDs). Previously, we have demonstrated that inhibition of methylation by periodate oxidized adenosine (Adox) results in a widening of the anterior neuropore (ANP) in our in vitro chick embryo model. Since DNA methylation is the chief regulator of gene expression, we hypothesize that inhibition of methylation by Adox in our in vitro chick embryo model will affect the expression of genes that may be involved in neurulation. In the present study, we therefore examined differential gene expression between Adox-treated and control chick embryos, using the Affymetrix Genechip Chicken Genome Array. METHODS: Chick embryos of 4/5 somites were cultured in vitro with saline (control) or Adox and cranial parts were excised. Gene expression profiling was determined using the Affymetrix Genechip Chicken Genome Array on RNA isolated from two pools of Adox-treated cranial parts (n = 12) and two pools of saline-treated cranial parts (n = 12). Microarray data were validated by QPCR analysis. RESULTS: In the Adox-treated chick embryos, 45 probesets were up-regulated (fold 2.0, p <0.05) and 32 probesets were down-regulated (fold 0.5, p <0.05). Of the 15 genes selected for QPCR analysis, the up-regulation of phosphoserine phosphatase (PSPH), unc-51-like kinase 1 (ULK1), and chemokine (C-X-C motif) ligand 12/stromal cell-derived factor 1 (CXCL12/SDF-1) was confirmed. CONCLUSIONS: Inhibition of methylation by Adox affects gene expression in our in vitro chick embryo model. Further research will focus on the gene-specific methylation patterns of PSPH, ULK1, and CXCL12/SDF-1 and the role of the products of these genes in neurulation.
No Effect of Red Clover-Derived Isoflavone Intervention on the Insulin-Like Growth Factor System in Women at Increased Risk of Colorectal Cancer
Vrieling, A. ; Rookus, M.A. ; Kampman, E. ; Bonfrer, J.M.G. ; Bosma, A. ; Cats, A. ; Doorn, J. van; Korse, C.M. ; Witteman, B.J.M. ; Leeuwen, F.E. van; van't Veer, L.J. ; Voskuil, D.W. - \ 2008
Cancer Epidemiology Biomarkers and Prevention 17 (2008)10. - ISSN 1055-9965 - p. 2585 - 2593.
healthy postmenopausal women - hormone replacement therapy - randomized controlled-trial - igf-binding-proteins - factor-i - prostate-cancer - soy protein - premenopausal women - antioxidant status - dna microarray
Background: Increased insulin-like growth factor (IGF)-I and IGF-II concentrations are related to increased colorectal cancer risk. Isoflavones have been associated with reduced colorectal cancer risk, and may affect the IGF system because of their weak estrogenic activity. The aim of the study was to investigate the effect of isolated isoflavones on serum concentrations of IGF system components. Materials and Methods: We conducted a randomized, placebo-controlled, double-blinded, crossover trial in four hospitals in the Netherlands to investigate the effect of an 8-week supplementation with red clover¿derived isoflavones (84 mg/d) on serum IGF-I concentrations. In addition, serum concentrations of IGF-II and IGF binding proteins (IGFBP)-1, IGFBP-2, and IGFBP-3 were assessed. Normal colorectal tissue biopsies were obtained after the first intervention period and mRNA expression of IGF-I, IGF-II, IGFBP-3, and IGF-IR was evaluated. Our study population consisted of 34 postmenopausal women with a family history of colorectal cancer or a personal history of colorectal adenomas. Results: Isoflavone supplementation did not significantly affect serum concentrations of total IGF-I (mean relative within-person difference; IGF-I, ¿2.0%; 95% confidence interval, ¿8.0% to 3.9%). IGF-II and IGFBPs were also not significantly altered after isoflavone supplementation. Colorectal tissue mRNA expression of IGF system components did not significantly differ between individuals on isoflavone supplementation and those who received placebo. Conclusions: The results of our trial, supported by a qualitative review of soy trials published to date, suggest that isoflavones do not significantly affect circulating levels of IGF system components. Increased levels of IGF-I, as observed in most of these trials, are likely due to simultaneous protein suppl
Treatment of iodine deficiency in school-age children increases 1GF-1 and IGFBP-3 concentrations and improvves somatic growth
Zimmermann, M.B. ; Jooste, P.L. ; Solomon Mabapa, N. ; Mbhenyane, X. ; Schoeman, S. ; Biebinger, R. ; Chaouki, N. ; Bozo, M. ; Grimci, L. ; Bridson, J. - \ 2007
Journal of Clinical Endocrinology and Metabolism 92 (2007)2. - ISSN 0021-972X - p. 437 - 442.
factor-i - thyroid-hormone - endemic goiter - rat - supplementation - cells - hyperthyroidism - hypothyroidism - schoolchildren - dysfunction
Objective: To determine if iodine repletion improves somatic growth in iodine-deficient children and to investigate the role of insulin-like growth factor (IGF)-1 and insulin-like growth factor binding protein (IGFBP)-3 in this effect. Design, participants, and interventions: Three prospective, double blind intervention studies were done: 1) in a 10 month study, severely iodine-deficient, 7-10 y-old Moroccan children (n = 71) were provided iodized salt and compared with children not using iodized salt; 2) in a 6 month study, moderately iodine-deficient, 10-12 y-old Albanian children (n = 310) were given 400 mg iodine as oral iodized oil or placebo; 3) in a 6 month study, mildly iodine-deficient 5-14 y-old South African children (n = 188) were given two doses of 200 mg iodine as oral iodized oil or placebo. At baseline and follow-up, height, weight, urinary iodine (UI), total thyroxine (TT4), thyroid-stimulating hormone (TSH) and IGF-I were measured; in Albania and South Africa, IGFBP-3 was also measured. Results: In all three studies, iodine treatment increased median UI to >100 µg/L, while median UI in the controls remained unchanged. In South Africa, iodine repletion modestly increased IGF-1, but did not have a significant effect on IGFBP-3, TT4 or growth. In Albania and Morocco, iodine repletion significantly increased TT4, IGF-1, IGFBP-3, weight-for-age z scores and height-for-age z scores. Conclusion: This is the first controlled study to clearly demonstrate that iodine repletion in school-age children increases IGF-1 and IGFBP-3 concentrations and improves somatic growth.
Lycopene supplementation elevates circulating insulin-like growth factor-binding protein-1 and-2 concentrations in persons at greater risk of colorectal cancer
Vrieling, A. ; Voskuil, D.W. ; Bonfrer, J.M. ; Korse, C.M. ; Doorn, J. ; Cats, A. ; Depla, A.C. ; Timmer, R. ; Witteman, B.J.M. ; Leeuwen, F.E. van; van't Veer, L.J. ; Rookus, M.A. ; Kampman, E. - \ 2007
American Journal of Clinical Nutrition 86 (2007)5. - ISSN 0002-9165 - p. 1456 - 1462.
factor-i - factor (igf)-i - factor system - igf-i - alpha-tocopherol - clinical-trial - human serum - c-peptide - dietary - carotenoids
Background: Higher circulating insulin-like growth factor I (IGF-I) concentrations have been related to a greater risk of cancer. Lycopene intake is inversely associated with cancer risk, and experimental studies have shown that it may affect the IGF system, possibly through an effect on IGF-binding proteins (IGFBPs). Objective: The objective of our study was to investigate the effect of an 8-wk supplementation with tomato-derived lycopene (30 mg/d) on serum concentrations of total IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3. Design: We conducted a randomized, placebo-controlled, double-blinded crossover study in 40 men and 31 postmenopausal women with a family history of colorectal cancer, a personal history of colorectal adenoma, or both. Results: Lycopene supplementation significantly (P = 0.01) increased serum IGFBP-1 concentrations in women (median relative difference between serum IGFBP-1 concentrations after lycopene supplementation and after placebo, 21.7%). Serum IGFBP-2 concentrations were higher in both men and women after lycopene supplementation than after placebo, but to a lesser extent (mean relative difference 8.2%; 95% CI: 0.7%, 15.6% in men and 7.8%; 95% CI: ¿5.0%, 20.6% in women). Total IGF-I, IGF-II, and IGFBP-3 concentrations were not significantly altered by lycopene supplementation. Conclusions: This is the first study known to show that lycopene supplementation may increase circulating IGFBP-1 and IGFBP-2 concentrations. Because of high interindividual variations in IGFBP-1 and IGFBP-2 effects, these results should be confirmed in larger randomized intervention studies
Isolated Isoflavones do not affect the circulating insulin-like growth factor system in men at increased colorectal cancer risk
Vrieling, A. ; Rookus, M.A. ; Kampman, E. ; Bonfrer, J.M.G. ; Korse, C.M. ; Doorn, J. van; Lampe, J.W. ; Cats, A. ; Witteman, B.J.M. ; Leeuwen, F.E. van; van't Veer, L.J. ; Voskuil, D.W. - \ 2007
The Journal of Nutrition 137 (2007)2. - ISSN 0022-3166 - p. 379 - 383.
estrogen replacement therapy - red-clover - factor-i - postmenopausal women - binding protein-3 - soy protein - clinical characteristics - premenopausal women - antioxidant status - human health
Epidemiological studies show that increased insulin-like growth factor (IGF)-I concentrations are related to increased colorectal cancer risk. A reduced colorectal cancer risk has been associated with isoflavones, which might affect the IGF-system because of their weak estrogenic activity. We conducted a randomized, placebo-controlled, double-blind crossover study to investigate the effect of an 8-wk isolated isoflavone supplementation (84 mg/d) on serum concentrations of total IGF-I, free IGF-I, total IGF-II, IGF binding protein (BP)-1, IGFBP-2, and IGFBP-3. Additionally, we investigated whether IGF-system component differences were related to concentrations of the more potent estrogenic isoflavone metabolite, equol. Our study population consisted of 37 men with a family history of colorectal cancer or a personal history of colorectal adenomas. Isoflavone supplementation did not significantly affect serum total IGF-I concentrations (relative difference between serum total IGF-I concentrations after isoflavone supplementation and after placebo: ¿1.3%, 95% CI ¿8.6 to 6.0%). Neither free IGF-I, nor total IGF-II, IGFBP-1, IGFBP-2, or IGFBP-3 concentrations were significantly altered. Interestingly, the change in serum IGF-I concentrations after isoflavone supplementation was negatively associated with serum equol concentrations (r = ¿0.49, P = 0.002). In conclusion, isolated isoflavones did not affect the circulating IGF-system in a male high-risk population for colorectal cancer. However, to our knowledge, this is the first study that suggests isoflavones might have an IGF-I lowering effect in equol producers only. This underlines the importance of taking into account equol status in future isoflavone intervention studies
Metabolic adaptation and hormonal regulation in young rabbit does during long-term caloric restriction and subsequent compensatory growth
Rommers, J.M. ; Boiti, C. ; Brecchia, G. ; Meijerhof, R. ; Noordhuizen, J.P.T.M. ; Decuypere, M.P. ; Kemp, B. - \ 2004
Animal Science 79 (2004)2. - ISSN 1357-7298 - p. 255 - 264.
feed restriction - thyroid-hormones - factor-i - prepubertal gilts - energy-intake - plasma - insulin - chickens - realimentation - performance
An experiment was performed to assess the metabolic adaptation and hormonal regulation in young female rabbits during long-term food restriction and subsequent compensatory growth during rearing. Feeding level was either ad libitum (AL, no. = 52) or restricted (R, no. = 52). From 6 to 12 weeks of age, food intake of R was kept at a constant level. This resulted in an increase in relative restriction as compared with AL to 0.54of AL intake at 12 weeks of age (restriction period). Thereafter food intake gradually increased to 0.95 of AL at 17 weeks of age (recovery period). During the last 5 days before insemination at 17.5 weeks of age, all animals were fed to appetite. Blood samples were taken weekly from 6 to 17 weeks of age from 11 animals in each group. Growth rate of R was reduced during the restricted period (29 (s.d. 2) v. 44 (s.d. 5) g/day for R and AL, respectively; P <0.05), but was higher in the recovery period (30 (s.d. 3) v. 27 (s.d. 4) g/day, respectively; P <0.05). At first insemination, AL rabbits were heavier than R (4202 (s.d. 388) v. 3798 (s.d. 220) g, respectively; P <0.001). During the restricted period, plasma glucose was constantly lower (P <0.05) in R. Insulin levels paralleled those of glucose, being lower (P <0.05) in R than in AL. Restriction reduced CP <0.05) circulating corticosterone and tri-iodothyronine (T3) levels in R. Leptin, non-esterified fatty acids, and plasma urea nitrogen levels were similar for AL and R during food restriction, whereas triglycerides were similar until 10 weeks of age, after which the levels were lower in R. During the recovery period, the food intake of the R but not AL rabbits increased. Insulin was the only hormone in R rabbits that had returned to levels found in AL rabbits by the 2nd week of the recovery period. Glucose, T3, and corticosterone levels returned to levels found in AL rabbits between 3 to 4 weeks after refeeding. Non-esterified fatty acids, triglycerides, and leptin were higher (P <0.05) in AL rabbits from 13 weeks of age onwards. The pattern of changes in the endocrine status during food restriction and compensatory growth in rabbits do conform with those from other species, although some specific changes may vary depending on the severity of food restriction and its duration.