The latter process is driven by ATP and is mediated by multidrug
resistance protein 2 (MRP2) [73]. The fact that the iv injection of
rabbits with AsIII and SeVI also resulted in the rapid biliary excretion of
[(GS)2AsSe]− (the latter species, however, was not detected in blood) implies
that it was formed in hepatocytes. This finding – in turn – could be
explained in terms of the reduction of the intravenously administered
SeVI after import into the liver by a selenate-reductase [69]. These findings
combined with the key role that HSe− plays in the mammalian metabolism
of Se and the synthesis of selenoproteins [74] suggested that
AsIII should inhibit selenoprotein biosynthesis. This hypothesis was recently
confirmed in mammalian cells [75,76] and underscores the toxicological
relevance of [(GS)2AsSe]−. The formation of [(GS)2AsSe]− in the
mammalian bloodstream has been reported to effect signal transduction
pathways [77,78]. Therefore, this species may also play an important role
with regard to the effect that As2O3 exerts in patients that are suffering
from promyelocytic leukemia [79,80].
The latter process is driven by ATP and is mediated by multidrugresistance protein 2 (MRP2) [73]. The fact that the iv injection ofrabbits with AsIII and SeVI also resulted in the rapid biliary excretion of[(GS)2AsSe]− (the latter species, however, was not detected in blood) impliesthat it was formed in hepatocytes. This finding – in turn – could beexplained in terms of the reduction of the intravenously administeredSeVI after import into the liver by a selenate-reductase [69]. These findingscombined with the key role that HSe− plays in the mammalian metabolismof Se and the synthesis of selenoproteins [74] suggested thatAsIII should inhibit selenoprotein biosynthesis. This hypothesis was recentlyconfirmed in mammalian cells [75,76] and underscores the toxicologicalrelevance of [(GS)2AsSe]−. The formation of [(GS)2AsSe]− in themammalian bloodstream has been reported to effect signal transductionpathways [77,78]. Therefore, this species may also play an important rolewith regard to the effect that As2O3 exerts in patients that are sufferingfrom promyelocytic leukemia [79,80].
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