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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Manganese species from human serum, cerebrospinal fluid analyzed by size exclusion chromatography-, capillary electrophoresis coupled to inductively coupled plasma mass spectrometry.

Manganese (Mn) at high concentrations can have adverse effects on health, mainly because of its toxicity to the central nervous system. Health impacts of Mn are known mostly from occupational health studies, but the exact mechanisms how Mn, being bound to transferrin (TF) in the blood, enters the brain--are unknown. Mn speciation at the neural barriers can help to obtain more information about the pathways and carriers. This paper summarizes investigations on the size distribution of Mn carriers (e.g. proteins, peptides, carbonic acids) in serum before the neural barriers and in cerebrospinal fluid (CSF) behind them as a first characterization step of the Mn carriers being involved in moving Mn across the neural barriers. Further identification of Mn-species in CSF was successfully achieved by CZE-inductively coupled plasma (ICP)-dynamic reaction cell (DRC)-mass spectrometry (MS). Serum samples showed Mn mean concentrations of 1.7+/-0.8 microg L(-1). The size distribution of Mn-carriers showed a main peak in the TF/albumin size fitting to the known physiological ligands. However, also an increasing Mn peak at 700 Da with increasing total Mn concentration was seen. Samples of CSF showed Mn mean concentrations of 2.6 microg L(-1)=48 nM. In CSF Mn was found to be mostly bound to low-molecular-mass (LMM)-Mn carriers in the range of 640-680 Da. This is similar to the LMM compound in serum and to Mn-citrate complexes suggested to be present in body fluids. Citrate concentration was 573 microM, thus being in huge excess compared to Mn. CSF was further analyzed by CZE-ICP-DRC-MS. Several Mn-species were monitored and mostly identified. The most abundant Mn-species was Mn-citrate at a concentration of around 0.7 microg Mn L(-1).[1]


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