TY  - JOUR
A1  - Danquah, Ina
A1  - Dobrucky, C. Lydia
A1  - Frank, Laura K.
A1  - Henze, Andrea
A1  - Amoako, Yaw A.
A1  - Bedu-Addo, George
A1  - Raila, Jens
A1  - Schulze, Matthias Bernd
A1  - Mockenhaupt, Frank P.
A1  - Schweigert, Florian J.
T1  - Vitamin A: potential misclassification of vitamin A status among patients with type 2 diabetes and hypertension in urban Ghana
JF  - The American journal of clinical nutrition : a publication of the American Society for Nutrition, Inc.
N2  - Background: Sub-Saharan Africa is facing a double burden of malnutrition: vitamin A deficiency (VAD) prevails, whereas the nutrition-related chronic conditions type 2 diabetes (T2D) and hypertension are emerging. Serum retinol a VAD marker increases in kidney disease and decreases in inflammation, which can partly be attributed to alterations in the vitamin A transport proteins retinol-binding protein 4 (RBP4) and prealbumin. Kidney dysfunction and inflammation commonly accompany T2D and hypertension.
 Objective: Among urban Ghanaians, we investigated the associations of T2D and hypertension with serum retinol as well as the importance of kidney function and inflammation in this regard.
 Design: A hospital-based, case-control study in individuals for risk factors of T2D, hypertension, or both was conducted in Kumasi, Ghana (328 controls, 197 with T2D, 354 with hypertension, and 340 with T2D plus hypertension). In 1219 blood samples, serum retinol, RBP4, and prealbumin were measured. Urinary albumin and estimated glomerular filtration rate (eGFR) defined kidney function. C-reactive protein (CRP) >5 mg/L indicated inflammation. We identified associations of T2D and hypertension with retinol by linear regression and calculated the contribution of RBP4, prealbumin, urinary albumin, eGFR, and CRP to these associations as the percentages of the explained variance of retinol.
 Results: VAD (retinol <1.05 mu mol/L) was present in 10% of this predominantly female, middle-aged, overweight, and deprived population. Hypertension, but not T2D, was positively associated with retinol (beta: 0.12; 95% CI: 0.08, 0,17), adjusted for age, sex, socioeconomic factors, anthropometric measurements, and lifestyle. In addition to RBP4 (72%) and prealbumin (22%), the effect of increased retinol on individuals with hypertension was mainly attributed to impaired kidney function (eGFR: 30%; urinary albumin: 5%) but not to inflammation.
 Conclusions: In patients with hypertension, VAD might be underestimated because of increased serum retinol in the context of kidney dysfunction. Thus, the interpretation of serum retinol in sub-Saharan Africa should account for hypertension status.
KW  - hypertension
KW  - inflammation
KW  - kidney dysfunction
KW  - type 2 diabetes
KW  - vitamin A deficiency
Y1  - 2015
U6  - https://doi.org/10.3945/ajcn.114.101345
SN  - 0002-9165
SN  - 1938-3207
VL  - 102
IS  - 1
SP  - 207
EP  - 214
PB  - American Society for Nutrition, Inc.
CY  - Bethesda
ER  - 
TY  - JOUR
A1  - Henze, Andrea
A1  - Raila, Jens
A1  - Kempf, Caroline
A1  - Reinke, Petra
A1  - Sefrin, Anett
A1  - Querfeld, Uwe
A1  - Schweigert, Florian J.
T1  - Vitamin A metabolism is changed in donors after living-kidney transplantation an observational study
JF  - Lipids in health and disease
N2  - Background: The kidneys are essential for the metabolism of vitamin A (retinol) and its transport proteins retinol-binding protein 4 (RBP4) and transthyretin. Little is known about changes in serum concentration after living donor kidney transplantation (LDKT) as a consequence of unilateral nephrectomy; although an association of these parameters with the risk of cardiovascular diseases and insulin resistance has been suggested. Therefore we analyzed the concentration of retinol, RBP4, apoRBP4 and transthyretin in serum of 20 living-kidney donors and respective recipients at baseline as well as 6 weeks and 6 months after LDKT.
 Results: As a consequence of LDKT, the kidney function of recipients was improved while the kidney function of donors was moderately reduced within 6 weeks after LDKT. With regard to vitamin A metabolism, the recipients revealed higher levels of retinol, RBP4, transthyretin and apoRBP4 before LDKT in comparison to donors. After LDKT, the levels of all four parameters decreased in serum of the recipients, while retinol, RBP4 as well as apoRBP4 serum levels of donors increased and remained increased during the follow-up period of 6 months.
 Conclusion: LDKT is generally regarded as beneficial for allograft recipients and not particularly detrimental for the donors. However, it could be demonstrated in this study that a moderate reduction of kidney function by unilateral nephrectomy, resulted in an imbalance of components of vitamin A metabolism with a significant increase of retinol and RBP4 and apoRBP4 concentration in serum of donors.
KW  - Donors
KW  - glomerular filtration rate
KW  - kidney transplantation
KW  - retinol
KW  - retinol-binding protein 4
KW  - transthyretin
Y1  - 2011
U6  - https://doi.org/10.1186/1476-511X-10-231
SN  - 1476-511X
VL  - 10
IS  - 23
PB  - BioMed Central
CY  - London
ER  - 
TY  - JOUR
A1  - Henze, Andrea
A1  - Espe, Katharina M.
A1  - Wanner, Christoph
A1  - Krane, Vera
A1  - Raila, Jens
A1  - Hocher, Berthold
A1  - Schweigert, Florian J.
A1  - Drechsler, Christiane
T1  - Transthyretin predicts cardiovascular outcome in hemodialysis patients with type 2 diabetes
JF  - Diabetes care
N2  - OBJECTIVE-BMI and albumin are commonly accepted parameters to recognize wasting in dialysis patients and are powerful predictors of morbidity and mortality. However, both parameters reveal limitations and may not cover the entire range of patients with wasting. The visceral protein transthyretin (TTR) may be helpful in overcoming the diagnostic and prognostic gap. Therefore, the aim of this study was to assess the association of TTR with morbidity and mortality in hemodialysis patients.
 RESEARCH DESIGN AND METHODS-The TTR concentration was determined in plasma samples of 1,177 hemodialysis patients with type 2 diabetes. Cox regression analyses were used to determine hazard ratios (HRs) for the risk of cardiovascular end points (CVEs) and mortality according to quartiles of TTR concentration for the total study cohort and the subgroups BMI >= 23 kg/m(2), albumin concentration >= 3.8 g/dL, and a combination of both.
 RESULTS-A low TTR concentration was associated with an increased risk for CVE for the total study cohort (HR 1.65 [95% CI 1.27-2.14]), patients with BMI >= 23 kg/m(2) (1.70 [1.22-2.37]), albumin >= 3.8 g/dL (1.68 [1.17-2.42]), and the combination of both (1.69 [1.13-2.53]). Additionally, a low TTR concentration predicted mortality for the total study cohort (1.79 [1.43-2.24]) and patients with BMI >= 23 kg/m(2) (1.46 [1.09-1.95]).
 CONCLUSIONS-The current study demonstrated that TTR is a useful predictor for cardiovascular outcome and mortality in diabetic hemodialysis patients. TTR was particularly useful in patients who were not identified to be at risk by BMI or albumin status.
Y1  - 2012
U6  - https://doi.org/10.2337/dc12-0455
SN  - 0149-5992
VL  - 35
IS  - 11
SP  - 2365
EP  - 2372
PB  - American Diabetes Association
CY  - Alexandria
ER  - 
TY  - JOUR
A1  - Döll, Stefanie
A1  - Djalali Farahani-Kofoet, Roxana
A1  - Zrenner, Rita
A1  - Henze, Andrea
A1  - Witzel, Katja
T1  - Tissue-specific signatures of metabolites and proteins in asparagus roots and exudates
JF  - Horticulture research
N2  - Comprehensive untargeted and targeted analysis of root exudate composition has advanced our understanding of rhizosphere processes. However, little is known about exudate spatial distribution and regulation. We studied the specific metabolite signatures of asparagus root exudates, root outer (epidermis and exodermis), and root inner tissues (cortex and vasculature). The greatest differences were found between exudates and root tissues. In total, 263 non-redundant metabolites were identified as significantly differentially abundant between the three root fractions, with the majority being enriched in the root exudate and/or outer tissue and annotated as 'lipids and lipid-like molecules' or 'phenylpropanoids and polyketides'. Spatial distribution was verified for three selected compounds using MALDI-TOF mass spectrometry imaging. Tissue-specific proteome analysis related root tissue-specific metabolite distributions and rhizodeposition with underlying biosynthetic pathways and transport mechanisms. The proteomes of root outer and inner tissues were spatially very distinct, in agreement with the fundamental differences between their functions and structures. According to KEGG pathway analysis, the outer tissue proteome was characterized by a high abundance of proteins related to 'lipid metabolism', 'biosynthesis of other secondary metabolites' and 'transport and catabolism', reflecting its main functions of providing a hydrophobic barrier, secreting secondary metabolites, and mediating water and nutrient uptake. Proteins more abundant in the inner tissue related to 'transcription', 'translation' and 'folding, sorting and degradation', in accord with the high activity of cortical and vasculature cell layers in growth- and development-related processes. In summary, asparagus root fractions accumulate specific metabolites. This expands our knowledge of tissue-specific plant cell function.
Y1  - 2021
U6  - https://doi.org/10.1038/s41438-021-00510-5
SN  - 2052-7276
VL  - 8
IS  - 1
PB  - Nanjing Agricultural Univ.
CY  - Nanjing
ER  - 
TY  - JOUR
A1  - Reeg, Sandra
A1  - Jung, Tobias
A1  - Castro, José Pedro
A1  - Davies, Kelvin J. A.
A1  - Henze, Andrea
A1  - Grune, Tilman
T1  - The molecular chaperone Hsp70 promotes the proteolytic removal of oxidatively damaged proteins by the proteasome
JF  - Free radical biology and medicine : the official journal of the Oxygen Society, a constituent member of the International Society for Free Radical Research
N2  - One hallmark of aging is the accumulation of protein aggregates, promoted by the unfolding of oxidized proteins. Unraveling the mechanism by which oxidized proteins are degraded may provide a basis to delay the early onset of features, such as protein aggregate formation, that contribute to the aging phenotype. In order to prevent aggregation of oxidized proteins, cells recur to the 20S proteasome, an efficient turnover proteolysis complex. It has previously been shown that upon oxidative stress the 26S proteasome, another form, dissociates into the 20S form. A critical player implicated in its dissociation is the Heat Shock Protein 70 (Hsp70), which promotes an increase in free 20S proteasome and, therefore, an increased capability to degrade oxidized proteins. The aim of this study was to test whether or not Hsp70 is involved in cooperating with the 20S proteasome for a selective degradation of oxidatively damaged proteins. Our results demonstrate that Hsp70 expression is induced in HT22 cells as a result of mild oxidative stress conditions. Furthermore, Hsp70 prevents the accumulation of oxidized proteins and directly promotes their degradation by the 20S proteasome. In contrast the expression of the Heat shock cognate protein 70 (Hsc70) was not changed in recovery after oxidative stress and Hsc70 has no influence on the removal of oxidatively damaged proteins. We were able to demonstrate in HT22 cells, in brain homogenates from 129/SV mice and in vitro, that there is an increased interaction of Hsp70 with oxidized proteins, but also with the 20S proteasome, indicating a role of Hsp70 in mediating the interaction of oxidized proteins with the 20S proteasome. Thus, our data clearly implicate an involvement of Hsp70 oxidatively damaged protein degradation by the 20S proteasome. c) 2016 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
KW  - Protein oxidation
KW  - Proteasome
KW  - Chaperone
KW  - HSP70
Y1  - 2016
U6  - https://doi.org/10.1016/j.freeradbiomed.2016.08.002
SN  - 0891-5849
SN  - 1873-4596
VL  - 99
SP  - 153
EP  - 166
PB  - Elsevier
CY  - New York
ER  - 
TY  - JOUR
A1  - Frede, Katja
A1  - Henze, Andrea
A1  - Khalil, Mahmoud
A1  - Baldermann, Susanne
A1  - Schweigert, Florian J.
A1  - Rawel, Harshadrai Manilal
T1  - Stability and cellular uptake of lutein-loaded emulsions
JF  - Journal of functional food
N2  - The carotenoid lutein can improve human health. Since only a fraction is absorbed from food, lutein supplementation might be recommended. Emulsions could be good carrier systems to improve the bioavailability of lutein. Six different emulsifier compositions were used in this study to prepare lutein-loaded emulsions: beta-lactoglobulin, beta-lactoglobulin/lecithin, Biozate 1, Biozate 1/lecithin, Been 20 and Tween 20/lecithin. The droplet size, resistance to creaming, lutein stability, cytotoxicity and lutein uptake by HT29 cells were investigated. The whey protein beta-lactoglobulin, the whey protein hydrolysate Biozate 1 and the combination with lecithin brought the most promising results. The small droplet sizes and resistance to creaming were an indication of physical stable emulsions. Furthermore, these emulsifiers prevented oxidation of lutein. The choice of emulsifier had a strong impact on the uptake by HT29 cells. The highest lutein absorption was observed with the combination of Biozate 1 and lecithin.
KW  - Lutein
KW  - Emulsion
KW  - Whey protein
KW  - Stability
KW  - Bioavailability
Y1  - 2014
U6  - https://doi.org/10.1016/j.jff.2014.03.011
SN  - 1756-4646
VL  - 8
SP  - 118
EP  - 127
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Münzner, Matthias
A1  - Tuvia, Neta
A1  - Deutschmann, Claudia
A1  - Witte, Nicole
A1  - Tolkachov, Alexander
A1  - Valai, Atijeh
A1  - Henze, Andrea
A1  - Sander, Leif E.
A1  - Raila, Jens
A1  - Schupp, Michael
T1  - Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by regulating cellular retinoid homeostasis and retinoic acid receptor alpha activity
JF  - Molecular and cellular biology
N2  - Retinoids are vitamin A (retinol) derivatives and complex regulators of adipogenesis by activating specific nuclear receptors, including the retinoic acid receptor (RAR) and retinoid X receptor (RXR). Circulating retinol-binding protein 4 (RBP4) and its membrane receptor STRA6 coordinate cellular retinol uptake. It is unknown whether retinol levels and the activity of RAR and RXR in adipocyte precursors are linked via RBP4/STRA6. Here, we show that STRA6 is expressed in precursor cells and, dictated by the apo-and holo-RBP4 isoforms, mediates bidirectional retinol transport that controls RAR alpha activity and subsequent adipocyte differentiation. Mobilization of retinoid stores in mice by inducing RBP4 secretion from the liver activated RAR alpha signaling in the precursor cell containing the stromal-vascular fraction of adipose tissue. Retinol-loaded holo-RBP4 blocked adipocyte differentiation of cultured precursors by activating RAR alpha. Remarkably, retinol-free apo-RBP4 triggered retinol efflux that reduced cellular retinoids, RAR alpha activity, and target gene expression and enhanced adipogenesis synergistically with ectopic STRA6. Thus, STRA6 in adipocyte precursor cells links nuclear RAR alpha activity to the circulating RBP4 isoforms, whose ratio in obese mice was shifted toward limiting the adipogenic potential of their precursors. This novel cross talk identifies a retinoldependent metabolic function of RBP4 that may have important implications for the treatment of obesity.
Y1  - 2013
U6  - https://doi.org/10.1128/MCB.00221-13
SN  - 0270-7306
SN  - 1098-5549
VL  - 33
IS  - 20
SP  - 4068
EP  - 4082
PB  - American Society for Microbiology
CY  - Washington
ER  - 
TY  - JOUR
A1  - Bobbert, Thomas
A1  - Raila, Jens
A1  - Schwarz, Franziska
A1  - Mai, Knut
A1  - Henze, Andrea
A1  - Pfeiffer, Andreas F. H.
A1  - Schweigert, Florian J.
A1  - Spranger, Joachim
T1  - Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness
N2  - Objective: Retinol is transported in a complex with retinol-binding protein 4 (RBP4) and transthyretin (TTR) in the circulation. While retinol is associated with various cardiovascular risk factors, the relation between retinol, RBP4, TTR and carotid intima media thickness (IMT) has not been analysed yet. Methods: Retinol, RBP4 and TTR were measured in 96 individuals and their relation to mean and maximal IMT was determined. Results: Mean IMT correlated with RBP4 (r = 0.335, p < 0.001), retinol (r = -0.241, p = 0.043), RBP/TTR ratio (r = 0.254, p = 0.025) and retinol/RBP4 ratio (r = -0.549, p < 0.001). Adjustment for age, sex, BMI, blood pressure, HDL/total cholesterol ratio, triglyceride, diabetes and smoking revealed that the retinol/RBP4 ratio was strongly and independently associated with mean IMT. Similar results were found for maximal IMT, which included the measurement of plaques. Conclusion: The data support that the transport complex of vitamin A is associated with the IMT, an established parameter of atherosclerosis. Changes in RBP4 saturation with retinol may link renal dysfunction and insulin resistance to atherosclerosis.
Y1  - 2010
UR  - http://www.sciencedirect.com/science/journal/00219150
U6  - https://doi.org/10.1016/j.atherosclerosis.2010.07.063
SN  - 0021-9150
ER  - 
TY  - GEN
A1  - Henze, Andrea
T1  - Proteinoxidation als Indikator des Alterungsphänotyps und Target einer individualisierten Ernährungsintervention (ProAID)
T1  - Protein Oxidation as an Indicator of the Aging Phenotype and Target of an individualized Nutritional Intervention (ProAID)
T2  - Ernährungs-Umschau : Forschung & Praxis
N2  - Oxidative posttranslationale Modifikationen endogener Proteine werden v. a. durch reaktive Sauerstoff- und Stickstoffspezies (engl:. Reactive Oxygen Species, ROS, reactive nitrogen species, RNS) hervorgerufen und können sowohl reversibel (z. B. Disulfidbindungen) als auch irreversibel (z. B. Proteincarbonyle) erfolgen [1–3]. Lange wurde angenommen, dass oxidative posttranslationale Proteinmodifikationen (oxPTPM) nur von untergeordneter Bedeutung für den Metabolismus sind. Tatsächlich handelt es sich jedoch um einen physiologischen Prozess, der über die Modulation der Proteinstruktur auch die Proteinfunktion (z. B. Enzymaktivität, Stabilität) und somit zahlreiche Stoffwechselwege wie den Energiestoffwechsel, die Immunfunktion, die vaskuläre Funktion sowie Apoptose und Genexpression beeinflussen kann. Die Bildung von oxPTPM ist dabei hochreguliert und hängt u. a. von der Proteinstruktur, der Verfügbarkeit von ROS und RNS sowie dem lokalen Mikromilieu der Zelle ab [2, 4].
Y1  - 2018
SN  - 0174-0008
VL  - 65
IS  - 10
SP  - M566
EP  - M567
PB  - Umschau-Zeitschriftenverl.
CY  - Frankfurt, Main
ER  - 
TY  - JOUR
A1  - Schutkowski, Alexandra
A1  - König, Bettina
A1  - Kluge, Holger
A1  - Hirche, Frank
A1  - Henze, Andrea
A1  - Schwerdtle, Tanja
A1  - Lorkowski, Stefan
A1  - Dawczynski, Christine
A1  - Gabel, Alexander
A1  - Grosse, Ivo
A1  - Stangl, Gabriele I.
T1  - Metabolic footprint and intestinal microbial changes in response to dietary proteins in a pig model
JF  - The journal of nutritional biochemistry
N2  - Epidemiological studies revealed that dietary proteins can contribute to the modulation of the cardiovascular disease risk. Still, direct effects of dietary proteins on serum metabolites and other health-modulating factors have not been fully explored. Here, we compared the effects of dietary lupin protein with the effects of beef protein and casein on the serum metabolite profile, cardiovascular risk markers and the fecal microbiome. Pigs were fed diets containing 15% of the respective proteins for 4 weeks. A classification analysis of the serum metabolites revealed six biomarker sets of two metabolites each that discriminated between the intake of lupin protein, lean beef or casein. These biomarker sets included 1- and 3-methylhistidine, betaine, carnitine, homoarginine and methionine. The study revealed differences in the serum levels of the metabolites 1- and 3- methylhistidine, homoarginine, methionine and homocysteine, which are involved in the one-carbon cycle. However, these changes were not associated with differences in the methylation capacity or the histone methylation pattern. With the exception of serum homocysteine and homoarginine levels, other cardiovascular risk markers, such as the homeostatic model assessment index, trimethylamine-N-oxide and lipids, were not influenced by the dietary protein source. However, the composition of the fecal microorganisms was markedly changed by the dietary protein source. Lupin-protein-fed pigs exhibited more species from the phyla Bacteroidetes and Firmicutes than the other two groups. In conclusion, different dietary protein sources induce distinct serum metabolic fingerprints, have an impact on the cardiovascular risk and modulate the composition of the fecal microbiome. (C) 2019 Elsevier Inc. All rights reserved.
KW  - Lupin
KW  - Beef
KW  - Casein
KW  - Pig
KW  - Biomarker
KW  - Microbiome
Y1  - 2019
U6  - https://doi.org/10.1016/j.jnutbio.2019.02.004
SN  - 0955-2863
SN  - 1873-4847
VL  - 67
SP  - 149
EP  - 160
PB  - Elsevier
CY  - New York
ER  -