Elevated levels of free iron / hypomyelination

ironjustice@aol.com · medicine forum Guru Joined: 28 Apr 2005 Posts: 1522

Iron contributes to dopamine-induced toxicity in oligodendrocyte
progenitors
Authors: Hemdan, S.; Almazan, G.

Source: Neuropathology & Applied Neurobiology, Volume 32, Number 4,
August 2006, pp. 428-440(13)

Publisher: Blackwell Publishing
Abstract:

S. Hemdan and G. Almazan (2006) Neuropathology and Applied
Neurobiology32, 000-000

Iron contributes to dopamine-induced toxicity in oligodendrocyte
progenitors

Iron is potentially toxic to oligodendrocyte progenitors due to its
high intracellular levels and its ability to catalyse oxidant-producing
reactions. Oxidative stress resulting from a hypoxic-ischaemic insult
has been implicated in death of oligodendrocyte progenitors that occurs
in the hypomyelinating disorder periventricular leucomalacia. Ischaemic
insults induce the release of various neurotransmitters, including
dopamine (DA), and we previously showed that DA is toxic to cultured
oligodendrocytes, by inducing oxidative stress and apoptosis.
Therefore, we investigated the role of iron in DA-induced cell death in
oligodendrocyte progenitors. Intracellular iron levels were altered
using an iron chelator, deferoxamine (DFO), and supplementation with
ferrous sulphate (FeSO4). Addition of FeSO4 to cultures increased
DA-induced toxicity as assessed by mitochondrial dehydrogenase activity
and cellular release of lactate dehydrogenase. Furthermore, FeSO4
increased expression of the stress protein heme oxygenase-1 (HO-1),
nuclear condensation and caspase-3 activation. In contrast,
preincubation with DFO reduced these events as well as cleavage of
a-spectrin, a caspase-3 substrate. In addition, FeSO4 reversed the
protective effect of DFO on DA-induced cytotoxicity, HO-1 expression
and caspase-3 activation. These results indicate that elevated levels
of free iron contribute to DA-induced toxicity in oligodendrocyte
progenitors.
Keywords: apoptosis; cell death; dopamine; iron; myelin;
oligodendrocytes; oxidative stress; periventricular leucomalacia

Document Type: Research article

DOI: 10.1111/j.1365-2990.2006.00757.x

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