@article{RawelFreyMeidtneretal.2006,
  author    = {Rawel, Harshadrai Manilal and Frey, Simone K. and Meidtner, Karina and Kroll, J{\"u}rgen and Schweigert, Florian J.},
  title     = {Determining the binding affinities of phenolic compounds to proteins by quenching of the intrinsic tryptophan fluorescence},
  series = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology},
  volume    = {50},
  journal   = {Molecular nutrition \& food research : bioactivity, chemistry, immunology, microbiology, safety, technology},
  number    = {8},
  publisher = {Wiley},
  address   = {Weinheim},
  issn      = {1613-4125},
  doi       = {10.1002/mnfr.200600013},
  pages     = {705 -- 713},
  year      = {2006},
  abstract  = {The noncovalent binding of selected phenolic compounds (chlorogenic-, ferutic-, gallic acid, quercetin, rutin, and isoquercetin) to proteins (HSA, BSA, soy glycinin, and lysozyme) was studied by an indirect method applying the quenching of intrinsic tryptophan fluorescence. From the data obtained, the binding constants were calculated by nonlinear regression (one site binding; y = Bx/k + x). It has been reported that tannins inhibit human salivary amylase and that these complexes may reduce the development of cariogenic plaques. Further, amylase contains two tryptophan residues in its active site. Therefore, in a second part of the study involving 31 human subjects, evidence was sought for noncovalent interactions between the phenols of green tea and saliva proteins as measured by the fluorescence intensity. Amylase activity was determined before and after the addition of green tea to saliva of 31 subjects. Forty percent of the subjects showed an increase in amylase activity contrary to studies reporting only a decrease in activity. The interactions of tannin with amylase result in a decrease of its activity. It still remains to be elucidated why amylase does not react uniformly under conditions of applying green tea to saliva. Further, in terms of using phenols as caries inhibitors this finding should be of importance.},
  language  = {en}
}
@article{RohnerFreyMothesetal.2011,
  author    = {Rohner, Fabian and Frey, Simone K. and Mothes, Ralf and Hurtienne, Andrea and Hartong, Simone and Bosso, Patrice Emery and Bui, Mai and Schweigert, Florian J. and Northrop-Clewes, Christine},
  title     = {Quantification of vitamin A in palm oil using a fast and simple portable device method validation and comparison to high-performance liquid chromatography},
  series = {International journal for vitamin and nutrition research},
  volume    = {81},
  journal   = {International journal for vitamin and nutrition research},
  number    = {5},
  publisher = {Hogrefe},
  address   = {Bern},
  issn      = {0300-9831},
  doi       = {10.1024/0300-9831/a000081},
  pages     = {335 -- 342},
  year      = {2011},
  abstract  = {Vitamin A deficiency continues to be a global public health problem. Fortification of oil with vitamin A is considered a cost-effective, feasible strategy to prevent this problem but quality control poses a challenge to program implementation. To overcome this, we have validated a newly developed device that quantitatively measures the content of retinyl palmitate in refined palm oil, is simple to use, and yields immediate results. Linearity of analysis rand from 2.5-30 mg retinol equivalents (RE)/kg of palm oil, with 2.5 mg RE/kg being the determination limit; inter- and intra-assay precision ranged from 1.4-7.1 To. Comparison with a high-performance Liquid chromatography method showed high agreement between the methods (R-2 = 0.92; Limits of Agreement: -1.24 mg to 2.53 mg RE/kg), and further comparisons illustrate that the new device is useful in low resource settings. This device offers a field- and user-friendly solution to quantifying the vitamin A content in refined palm oil.},
  language  = {en}
}
@article{RohnerGarrettLaillouetal.2012,
  author    = {Rohner, Fabian and Garrett, Greg S. and Laillou, Arnaud and Frey, Simone K. and Mothes, Ralf and Schweigert, Florian J. and Locatelli-Rossi, Lorenzo},
  title     = {Validation of a user-friendly and rapid method for quantifying iodine content of salt},
  series = {Food and nutrition bulletin},
  volume    = {33},
  journal   = {Food and nutrition bulletin},
  number    = {4},
  publisher = {International Nutrition Foundation},
  address   = {Boston},
  issn      = {0379-5721},
  pages     = {S330 -- S335},
  year      = {2012},
  abstract  = {Background. Despite considerable progress made in the past decade through salt iodization programs, over 2 billion people worldwide still have inadequate iodine intake, with devastating consequences for brain development and intellectual capacity. To optimize these programs with regard to salt iodine content, careful monitoring of salt iodine content is essential, but few methods are available to quantitatively measure iodine concentration in a simple, fast, and safe way. Objective. We have validated a newly developed device that quantitatively measures the content of potassium iodate in salt in a simple, safe, and rapid way. Methods. The linearity, determination and detection limit, and inter- and intra-assay variability of this colorimetric method were assessed and the method was compared with iodometric titration, using salt samples from several countries. Results. Linearity of analysis ranged from 5 to 75 mg/kg iodine, with I mg/kg being the determination limit; the intra- and interassay imprecision was 0.9\%, 0.5\%, and 0.7\% and 1.5\%, 1.7\%, and 2.5\% for salt samples with iodine contents of 17, 30, and 55 mg/kg, respectively; the interoperator imprecision for the same samples was 1.2\%, 4.9\%, and 4.7\%, respectively. Comparison with the iodometric method showed high agreement between the methods (R-2 = 0.978; limits of agreement, -10.5 to 10.0 mg/kg). Conclusions. The device offers a field- and user-friendly solution to quantifying potassium iodate salt content reliably. For countries that use potassium iodide in salt iodization programs, further validation is required.},
  language  = {en}
}
@article{HenzeFreyRailaetal.2010,
  author    = {Henze, Andrea and Frey, Simone K. and Raila, Jens and Scholze, Alexandra and Spranger, Joachim and Weickert, Martin O. and Tepel, Martin and Zidek, Walter and Schweigert, Florian J.},
  title     = {Alterations of retinol-binding protein 4 species in patients with different stages of chronic kidney disease and their relation to lipid parameters},
  issn      = {0006-291X},
  doi       = {10.1016/j.bbrc.2010.01.082},
  year      = {2010},
  abstract  = {Retinol-binding protein 4 (RBP4) is elevated in patients with chronic kidney disease (CKD) and has been discussed as marker of kidney function. In addition to an elevated concentration, the existence of truncated RBP4 species, RBP4-L (truncated at last C-terminal leucine) and RBP4-LL (truncated at both C-terminal leucines), has been reported in serum of hemodialysis patients. Since little is known about the occurrence of RBP4 species during the progression of CKD it was the aim of this study to analyse this possible association. The presence of RBP4, RBP4-L, RBP4- LL and transthyretin (TTR) was assessed in serum of 45 healthy controls and 52 patients with stage 2-5 of CKD using ELISA and RBP4 immunoprecipitation with subsequent MALDI-TOF-MS analysis. A reduction of glomerular filtration rate was accompanied by a gradual elevation of RBP4 serum levels and relative amounts of RBP4-LL. Correlation analysis revealed a strong association of the RBP4-TTR ratio with parameters of lipid metabolism and with diabetes-related factors. In conclusion, RBP4 serum concentration and the appearance of RBP4-LL seem to be influenced by kidney function. Furthermore, the RBP4-TTR ratio may provide diagnostic potential with regard to metabolic complications in CKD patients.},
  language  = {en}
}
@article{FreySprangerHenzeetal.2009,
  author    = {Frey, Simone K. and Spranger, Joachim and Henze, Andrea and Pfeiffer, Andreas F. H. and Schweigert, Florian J. and Raila, Jens},
  title     = {Factors that influence retinol-binding protein 4-transthyretin interaction are not altered in overweight subjects and overweight subjects with type 2 diabetes mellitus},
  issn      = {0026-0495},
  doi       = {10.1016/j.metabol.2009.05.003},
  year      = {2009},
  abstract  = {Retinol-binding protein 4 (RBP4) is an adipokine bound in plasma to transthyretin (TTR), which prevents its glomerular filtration and subsequent catabolism in the kidney. Alterations of this interaction have been Suggested to be implicated in the elevation of RBP4 that are thought to contribute to the development Of insulin resistance associated with obesity and type 2 diabetes mellitus (T2DM). However, the factors linking RBP4 to TTR in humans are not clear. Therefore, this Study evaluated parameters influencing the RBP4-TTR interaction and their relation to obesity and T2DM. The RBP4 and TTR levels were quantified in plasma of 16 lean controls, 28 overweight controls, and 14 overweight T2DM patients by enzyme-linked immunosorbent assay. Transthyretin isoforms involved in RBP4 binding were determined by linear matrix-assisted laser desorption/ionization-time of flight-mass spectrometry after RBP4 coimmunoprecipitation. Holo-RBP4 (retinol-bound) and apo-RBP4 (retinol-free) were assessed by immunoblotting using nondenaturating polyacrylamide gel electrophoresis. Plasma levels of both RBP4 and TTR did not differ among the groups of lean controls, overweight controls, and overweight T2DM subjects. Using RBP4 immunoprecipitation, 4 mass signals were observed for TTR representing native, S-cysteinylated, S-cysteinglycinylated, and S-glutathionylated TTR. No differences in peak intensity of TTR isoforms were observed among the groups. Moreover, no differences in the ratio of holo- and apo-RBP4 were evident. The results suggest that circulating RBP4 and TTR were not affected by human obesity or T2DM, which might be attributed to the absence of alterations of TTR isoforms and the ratio of holo- and apo-RBP4 that might modify the TTR-RBP4 interaction.},
  language  = {en}
}
@article{FreyHenzeNagletal.2009,
  author    = {Frey, Simone K. and Henze, Andrea and Nagl, Britta and Raila, Jens and Scholze, Alexandra and Tepel, Martin and Schweigert, Florian J. and Zidek, Walter},
  title     = {Effect of renal replacement therapy on retinol-binding protein 4 isoforms},
  issn      = {0009-8981},
  doi       = {10.1016/j.cca.2008.11.008},
  year      = {2009},
  abstract  = {Background: Retinol-binding protein 4 (RBP4) levels are elevated in the serum of patients with kidney dysfunction. We recently showed that RBP4 isoforms including apo-RBP4 (RBP4 not bound to retinol) and RBP4 truncated at the C-terminus (RBP4-L, RBP4-LL) are increased in the serum of patients with kidney diseases but not in serum of patients with various liver diseases. The aim of this study was to investigate the effect of renal replacement therapy on RBP4 isoforms. Methods: We investigated serum levels of RBP4, apo-RBP4, holo-RBP4, RBP4-L, RBP4-LL, retinol and transthyretin (TTR) in 18 hemodialysis (HD) patients, 30 patients after renal transplantation (RTx) and in 35 healthy controls. RBP4 and TTR levels were measured by enzyme-linked immunosorbent assay, apo- and holo-RBP4 by native electrophoresis, retinol by high performance liquid chromatography and RBP4-L and RBP4-LL were analyzed by mass spectrometry. Results: HD and RTx patients had elevated RBP4, apo-RBP4 and RBP4-LL levels compared to controls. RTx patients had elevated amounts of RBP4-L compared to controls and elevated RBP4 and apo-RBP4 levels compared to HD patients. Conclusion: The results demonstrate a strong correlation between kidney function and RBP4 isoforms and provide data for investigating the relation of RBP4 and insulin resistance in these patients.},
  language  = {en}
}
@article{ZizolaFreyJitngarmkusoletal.2010,
  author    = {Zizola, C. F. and Frey, Simone K. and Jitngarmkusol, S. and Kadereit, Bert and Yan, N. and Vogel, Silke},
  title     = {Cellular retinol-binding protein type I (CRBP-I) regulates adipogenesis},
  issn      = {0270-7306},
  doi       = {10.1128/Mcb.00014-10},
  year      = {2010},
  abstract  = {Adipogenesis is governed by a well-documented cascade of transcription factors. However, less is known about non-transcription factors that govern early stages of adipogenesis. Here we show that cellular retinol-binding protein type I (CRBP-I), a small cytosolic binding protein for retinol and retinaldehyde, is specifically restricted to preadipocytes in white adipose tissue. The absence of CRBP-I in mice (CRBP-I-KO mice) leads to increased adiposity. Despite increased adiposity, CRBP-I-KO mice remain more glucose tolerant and insulin sensitive during high-fat-diet feeding. 3T3-L1 cells deficient in CRBP-I or mouse embryonic fibroblasts derived from CRBP-I-KO mice had increased adipocyte differentiation and triglyceride (TG) accumulation. This was due to increased expression and activity of PPAR gamma, while other transcription factor pathways in early and late differentiation remained unchanged. Conversely, the overexpression of CRBP-I in 3T3-L1 cells results in decreased TG accumulation. In conclusion, CRBP-I is a cytosolic protein specifically expressed in preadipocytes that regulates adipocyte differentiation in part by affecting PPAR gamma activity.},
  language  = {en}
}
@phdthesis{Frey2009,
  author    = {Frey, Simone K.},
  title     = {Investigations on extra- and intracellular retinol-binding proteins},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-31428},
  school      = {Universit{\"a}t Potsdam},
  year      = {2009},
  abstract  = {The fat-soluble vitamin A, which is chemically referred to retinol (ROH), is known to be essential for the process of vision, the immune system but also for cell differentiation and proliferation. Recently, ROH itself has been reported to be involved in adipogenesis and a ROH transport protein, the retinol-binding protein 4 (RBP4), in insulin resistance and type 2 diabetes. However, there is still considerable scientific debate about this relation. With the increasing amount of studies investigating the relation of ROH in obesity and type 2 diabetes, basic research is an essential prerequisite for interpreting these results. This thesis enhances the knowledge on this relation by reviewing ROH metabolism on extra- and intracellular level. Aim 1: In the blood stream ROH is transported in a complex with RBP4 and a second protein, transthyretin (TTR), to the target cells. The levels of RBP4 and TTR are influenced by several factors but mainly by liver and kidney function. The reason for that is that liver and the kidneys are the sites of RBP4 synthesis and catabolism, respectively. Interestingly, obesity and type 2 diabetes involve disorders of the liver and the kidneys. Therefore the aim was to investigate factors that influence RBP4 and TTR levels in relation to obesity and type 2 diabetes (Part 1). Aim 2: Once arrived in the target cell ROH is bound to cellular retinol-binding protein type I (CRBP-I) and metabolised: ROH can either be stored as retinylesters or it can be oxidised to retinoic acid (RA). By acting as a transcription factor in the nucleus RA may influence processes such as adipogenesis. Therefore vitamin A has been postulated to be involved in obesity and type 2 diabetes. CRBP-I is known to mediate the storage of ROH in the liver, but the extra-hepatic metabolism and the functions of CRBP-I are not well known. This has been investigated in Part 2 of this work. Material \& Methods: RBP4 and TTR levels were investigated by ELISA in serum samples of human subjects with overweight, type 2 diabetes, kidney or liver dysfunction. Molecular alterations of the RBP4 and TTR protein structure were analysed by MALDI-TOF mass spectrometry. The functions of intracellular CRBP-I were investigated in CRBP-I knock-out mice in liver and extra-hepatic tissues by measuring ROH levels as well as the levels of its storage form, the retinylesters, using reverse phase HPLC. The postprandial uptake of ROH into tissues was analysed using labelled ROH. The mRNA levels of enzymes that metabolize ROH were examined by real-time polymerase chain reaction (RCR). Results: The previous published results showing increased RBP4 levels in type 2 diabetic patients could not be confirmed in this work. However, it could be shown that during kidney dysfunction RBP4 levels are increased and that RBP4 and TTR levels are decreased during liver dysfunction. The important new finding of this work is that increased RBP4 levels in type 2 diabetic mice were increased when kidney function was decreased. Thus an increase in RBP4 levels in type 2 diabetes may be the effect of a reduced kidney function which is common in type 2 diabetes. Interestingly, during severe kidney dysfunction the molecular structure of RBP4 and TTR was altered in a specific manner which was not the case during liver diseases and type 2 diabetes. This underlines the important function of the kidneys in RBP4 metabolism. CRBP-I has been confirmed to be responsible for the ROH storage in the liver since CRBP-I knock-out mice had decreased ROH and retinylesters (the storage form of ROH) levels in the liver. Interestingly, in the adipose tissue (the second largest ROH storage tissue in the body) ROH and retinylesters levels were higher in the CRBP-I knock-out compared to the wild-type mice. It could be shown in this work that a different ROH binding protein, cellular retinol-binding protein type III, is upregulated in CRBP-I knock-out mice. Moreover enzymes were identified which mediate very efficiently ROH esterification in the adipose tissue of the knock-out mice. In the pancreas there was a higher postprandial ROH uptake in the CRBP-I knock-out compard to wild-type mice. Even under a vitamin A deficient diet the knock-out animals had ROH and retinylesters levels which were comparable to wild-type animals. These results underline the important role of ROH for insulin secretion in the pancreas. Summing up, there is evidence that RBP4 levels are more determined by kidney function than by type 2 diabetes and that specific molecular modifications occur during kidney dysfunction. The results in adipose tissue and pancreas of CRBP-I knock-out mice support the hypothesis that ROH plays an important role in glucose and lipid metabolism.},
  language  = {en}
}