Abstract
We have observed that oxidation of Mn(III) ion in several manganese chelates to a Mn(IV) state occurs in the presence of apo-transferrin, and at the same time facile up-take of manganese ion by apo-transferrin proceeds. This clearly shows that much manganese ions can be transported to the brain by transferrin under the certain conditions, which may lead to manganism. Based on these results we have prepared the new chelate to capture only the Mn(III) and Mn(IV) ions selectively, but not Mn(II) ion, and to remove these manganese ions from the solution without toxicity.
Highlights
Elevated occupational exposures to manganese are known to cause significant neurotoxicity, and epidemiologic studies have suggested that a relationship between elevated manganese exposure and an increased risk for parkinsonian disturbances, called manganism, the exact mechanisms underlying the neurotoxic effects of manganese remain unclear (Dobson et al, 2004; Choi et al, 2010)
The addition of colorless apo-transferrin to the aged pale-brown Mn(dpea) complex solution immediately induced the color change to dark-brown, and in our previous paper we have concluded that the dark-brown solution derived from apo-transferrin and the aged pale-brown Mn-dpea solution should be due to the formation of Mn(III)-phenolate bonding in Mn(III)-transferrin (Abe et al, 2008)
It seems very rational to assume that formation of a Mn(IV) species in the solution plays a key step for the transport of a manganese ion to apo-transferrin, which should be supported by the fact that facile transport of manganese ion was observed in the solution containing apo-transferrin and a binuclear Mn(III)/Mn(IV) complex with di-μ-oxo-bridge (Abe et al, 2008)
Summary
Elevated occupational exposures to manganese are known to cause significant neurotoxicity, and epidemiologic studies have suggested that a relationship between elevated manganese exposure and an increased risk for parkinsonian disturbances, called manganism, the exact mechanisms underlying the neurotoxic effects of manganese remain unclear (Dobson et al, 2004; Choi et al, 2010). Several authors strongly suggest transport of trivalent manganese complexed to transferrin into the brain capillary endothelium, the exact mechanisms underlying the transport of manganese into the brain by transferrin remain unclear (Heilig et al, 2006). In our previous study we investigated the manganese ion uptake by apo-transferrin in terms of the capillary electrophoresis method (Abe et al, 2008), and obtained the clear evidence that oxidation state, +3 and binuclear unit of a manganese chelate are critical factors for the facile uptake by apo-transferrin, similar to that observed for Fe(III) species (Nishida et al, 2007). In this study we observed that facile oxidation of Mn(III) ion in several manganese chelates to a Mn(IV) state occurs in the reaction mixture containing apo-transferrin The significance of this oxidase-like function of apo-transferrin will be developed in this study
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