Abstract
Background: Transition metals play a crucial role in brain metabolism: since they exist in different oxidation states they are involved in ROS generation, but they are also co-factors of enzymes in cellular energy metabolism or oxidative defense. Methods: Paired serum and cerebrospinal fluid (CSF) samples were analyzed for iron, zinc, copper and manganese as well as for speciation using SEC-ICP-DRC-MS. Brain extracts from Mn-exposed rats were additionally analyzed with SEC-ICP-DRC-MS. Results: The concentration patterns of transition metal size fractions were correlated between serum and CSF: Total element concentrations were significantly lower in CSF. Fe-ferritin was decreased in CSF whereas a LMW Fe fraction was relatively increased. The 400–600 kDa Zn fraction and the Cu-ceruloplasmin fraction were decreased in CSF, by contrast the 40–80 kDa fraction, containing Cu- and Zn-albumin, relatively increased. For manganese, the α-2-macroglobulin fraction showed significantly lower concentration in CSF, whereas the citrate Mn fraction was enriched. Results from the rat brain extracts supported the findings from human paired serum and CSF samples. Conclusions: Transition metals are strictly controlled at neural barriers (NB) of neurologic healthy patients. High molecular weight species are down-concentrated along NB, however, the Mn-citrate fraction seems to be less controlled, which may be problematic under environmental load.
Highlights
Introduction published maps and institutional affilThe first-row transition metals iron (Fe), manganese (Mn), zinc (Zn) and copper (Cu) can exist in multiple oxidation states and participate in electron transfer reactions that are fundamental to sustain life for all organisms that undertake oxidative metabolism.Approximately one-third of the human proteome is bound to metals [1,2]
We revealed that all metals were significantly down-concentrated in cerebrospinal fluid (CSF) compared to corresponding serum samples and demonstrated Q(CSF/Serum) ratios similar to those reported elsewhere [37]
Using our Size exclusion chromatography (SEC)-ICP-dynamic reaction cell (DRC)-MS approach, we further sufficiently separated by the fact that the turnover of Zn in the brain is much slower compared to peripheral tissue and less prone to alterations [31]
Summary
Introduction published maps and institutional affilThe first-row transition metals iron (Fe), manganese (Mn), zinc (Zn) and copper (Cu) can exist in multiple oxidation states and participate in electron transfer reactions that are fundamental to sustain life for all organisms that undertake oxidative metabolism.Approximately one-third of the human proteome is bound to metals [1,2]. The first-row transition metals iron (Fe), manganese (Mn), zinc (Zn) and copper (Cu) can exist in multiple oxidation states and participate in electron transfer reactions that are fundamental to sustain life for all organisms that undertake oxidative metabolism. Transition metals play a crucial role in brain metabolism: since they exist in different oxidation states they are involved in ROS generation, but they are co-factors of enzymes in cellular energy metabolism or oxidative defense. Methods: Paired serum and cerebrospinal fluid (CSF) samples were analyzed for iron, zinc, copper and manganese as well as for speciation using SEC-ICP-DRC-MS. Results: The concentration patterns of transition metal size fractions were correlated between serum and CSF: Total element concentrations were significantly lower in CSF. The α-2-macroglobulin fraction showed significantly lower concentration in CSF, whereas the citrate Mn fraction was enriched
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