108 research outputs found
A seven day running training period increases basal urinary hepcidin levels as compared to cycling
BACKGROUND: This investigation compared the effects of an extended period of weight-bearing (running) vs. non-weight-bearing (cycling) exercise on hepcidin production and its implications for iron status. METHODS: Ten active males performed two separate exercise training blocks with either running (RTB) or cycling (CTB) as the exercise mode. Each block consisted of five training sessions (Day 1, 2, 4, 5, 6) performed over a seven day period that were matched for exercise intensity. Basal venous blood samples were obtained on Day 1 (D1), and on Recovery Days 3 (R3) and 7 (R7) to assess iron status, while basal and 3 h post-exercise urinary hepcidin levels were measured on D1, D2, D6, as well as R3 and R7 (basal levels only) for each condition. RESULTS: Basal urinary hepcidin levels were significantly elevated (p </= 0.05) at D2, R3 and R7 as compared to D1 in RTB. Furthermore, 3 h post-exercise urinary hepcidin levels on D1 were also significantly higher in RTB compared to CTB (p </= 0.05). In CTB, urinary hepcidin levels were not statistically different on D1 as compared to R7. Iron parameters were not significantly different at D1 compared to R3 and R7 during both conditions. CONCLUSIONS: These results suggest that basal hepcidin levels may increase over the course of an extended training program, especially if a weight-bearing exercise modality is undertaken. However, despite any variations in hepcidin production, serum iron parameters in both RTB and CTB were unaffected, possibly due to the short duration of each training block. In comparing running to cycling, non-weight-bearing activity may require more training sessions, or sessions of extended duration, before any significant changes in basal hepcidin levels appear. Chronic elevations in hepcidin levels may help to explain the high incidence of iron deficiency in athletes
Advances in Quantitative Hepcidin Measurements by Time-of-Flight Mass Spectrometry
Assays for the detection of the iron regulatory hormone hepcidin in plasma or urine have not yet been widely available, whereas quantitative comparisons between hepcidin levels in these different matrices were thus far even impossible due to technical restrictions. To circumvent these limitations, we here describe several advances in time-of flight mass spectrometry (TOF MS), the most important of which concerned spiking of a synthetic hepcidin analogue as internal standard into serum and urine samples. This serves both as a control for experimental variation, such as recovery and matrix-dependent ionization and ion suppression, and at the same time allows value assignment to the measured hepcidin peak intensities. The assay improvements were clinically evaluated using samples from various patients groups and its relevance was further underscored by the significant correlation of serum hepcidin levels with serum iron indices in healthy individuals. Most importantly, this approach allowed kinetic studies as illustrated by the paired analyses of serum and urine samples, showing that more than 97% of the freely filtered serum hepcidin can be reabsorbed in the kidney. Thus, the here reported advances in TOF MS-based hepcidin measurements represent critical steps in the accurate quantification of hepcidin in various body fluids and pave the way for clinical studies on the kinetic behavior of hepcidin in both healthy and diseased states
Functional analysis of the secretory precursor processing machinery of Bacillus subtilis:identification of a eubacterial homolog of archaeal and eukaryotic signal peptidases
Towards the Human Colorectal Cancer Microbiome
Multiple factors drive the progression from healthy mucosa towards sporadic
colorectal carcinomas and accumulating evidence associates intestinal bacteria
with disease initiation and progression. Therefore, the aim of this study was to
provide a first high-resolution map of colonic dysbiosis that is associated with
human colorectal cancer (CRC). To this purpose, the microbiomes colonizing colon
tumor tissue and adjacent non-malignant mucosa were compared by deep rRNA
sequencing. The results revealed striking differences in microbial colonization
patterns between these two sites. Although inter-individual colonization in CRC
patients was variable, tumors consistently formed a niche for
Coriobacteria and other proposed probiotic bacterial
species, while potentially pathogenic Enterobacteria were
underrepresented in tumor tissue. As the intestinal microbiota is generally
stable during adult life, these findings suggest that CRC-associated
physiological and metabolic changes recruit tumor-foraging commensal-like
bacteria. These microbes thus have an apparent competitive advantage in the
tumor microenvironment and thereby seem to replace pathogenic bacteria that may
be implicated in CRC etiology. This first glimpse of the CRC microbiome provides
an important step towards full understanding of the dynamic interplay between
intestinal microbial ecology and sporadic CRC, which may provide important leads
towards novel microbiome-related diagnostic tools and therapeutic
interventions
Mass Spectrometry Analysis of Hepcidin Peptides in Experimental Mouse Models
The mouse is a valuable model for unravelling the role of hepcidin in iron homeostasis, however, such studies still report hepcidin mRNA levels as a surrogate marker for bioactive hepcidin in its pivotal function to block ferroportin-mediated iron transport. Here, we aimed to assess bioactive mouse Hepcidin-1 (Hep-1) and its paralogue Hepcidin-2 (Hep-2) at the peptide level. To this purpose, fourier transform ion cyclotron resonance (FTICR) and tandem-MS was used for hepcidin identification, after which a time-of-flight (TOF) MS-based methodology was exploited to routinely determine Hep-1 and -2 levels in mouse serum and urine. This method was biologically validated by hepcidin assessment in: i) 3 mouse strains (C57Bl/6; DBA/2 and BABL/c) upon stimulation with intravenous iron and LPS, ii) homozygous Hfe knock out, homozygous transferrin receptor 2 (Y245X) mutated mice and double affected mice, and iii) mice treated with a sublethal hepatotoxic dose of paracetamol. The results showed that detection of Hep-1 was restricted to serum, whereas Hep-2 and its presumed isoforms were predominantly present in urine. Elevations in serum Hep-1 and urine Hep-2 upon intravenous iron or LPS were only moderate and varied considerably between mouse strains. Serum Hep-1 was decreased in all three hemochromatosis models, being lowest in the double affected mice. Serum Hep-1 levels correlated with liver hepcidin-1 gene expression, while acute liver damage by paracetamol depleted Hep-1 from serum. Furthermore, serum Hep-1 appeared to be an excellent indicator of splenic iron accumulation. In conclusion, Hep-1 and Hep-2 peptide responses in experimental mouse agree with the known biology of hepcidin mRNA regulators, and their measurement can now be implemented in experimental mouse models to provide novel insights in post-transcriptional regulation, hepcidin function, and kinetics
A seven day running training period increases basal urinary hepcidin levels as compared to cycling
Signal peptidases of Bacillus subtilis. A functional analysis.
A common feature in cells of all living organisms is the export of proteins from their site of synthesis, usually the cytoplasm, to other destinations either inside or outside the cell. To
achieve this, transported proteins are generally synthesized as a precursor with an aminoterminal signal peptide, which is recognized and exported by cellular sorting and translocation machineries. Although the primary structure of signal peptides is poorly conserved, usually three functional domains are present: first, a positively-charged amino terminus (N-region); second, a central hydrophobic domain (H-region); and third, a polar caroxyl-termindaol main (C-region), specifying the signal peptidase (S Pase) cleavage site.
Zie: Summary and general conclusions.
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