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demonstrating a significant role for iron in regulation of glutamate production
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Am J Physiol Cell Physiol. 2004 Dec 21; [Epub ahead of print] Related Articles,
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Iron alters glutamate secretion by regulating cytosolic aconitase activity.

McGahan MC, Harned J, Mukunnemkeril M, Goralska M, Fleisher LN, Ferrell J.

Department of Molecular Biomedical Sciences, North Carolina State University,
Raleigh, NC, USA.

Glutamate has many important physiological functions including its role as a
neurotransmitter in the retina and CNS. We have made the novel observations
that retinal pigment epithelial cells underlying and intimately interacting
with the retina secrete glutamate and this secretion is significantly affected
by iron. In addition, iron increased secretion of glutamate in cultured lens
and neuronal cells indicating that this may be a common mechanism for
regulation of glutamate production in many cell types. The activity of the iron
dependent enzyme, cytosolic aconitase (c-aconitase), is increased by iron. The
conversion of citrate to isocitrate by c-aconitase is the first step in a three
step process leading to glutamate formation. In the present study, iron
increased aconitase activity and this increase was associated with an increase
in glutamate secretion. Inhibition of c-aconitase by oxalomalate decreased
glutamate secretion and completely inhibited the iron induced increase in
glutamate secretion. Derangements in both glutamate secretion and iron
metabolism have been noted in neurological diseases and in retinal
degeneration. The results of the present investigation are the first to provide
a functional link between these two physiologically important substances by
demonstrating a significant role for iron in regulation of glutamate production
and secretion in mammalian cells resulting from iron regulation of aconitase
activity. Glutamatergic systems are found in many non-neuronal tissues. In the
present study we provide the first evidence that in addition to secreting
glutamate, retinal pigment epithelial cells express the vesicular glutamate
transporter, VGLUT1, and that regulated vesicular release of glutamate from
these cells can be inhibited by riluzole.

PMID: 15613494 [PubMed - as supplied by publisher]

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