<<snip>>
The antioxidant, TPPB, which targets mitochondria, protected the
oligodendrocytes from the iron-mediated cytotoxicity,
<<snip>>
Glia. 2005 Nov 15;52(3):199-208. Related Articles, Links
Cytokine toxicity to oligodendrocyte precursors is mediated by iron.
Zhang X, Haaf M, Todorich B, Grosstephan E, Schieremberg H, Surguladze
N, Connor JR.
Department of Neurosurgery, Pennsylvania State University, College of
Medicine Hershey, PA 17033, USA.
Inflammatory processes play a key role in the pathogenesis of a number
of common neurodegenerative disorders such as Alzheimer's disease (AD),
Parkinson's disease (PD), and multiple sclerosis (MS). Abnormal iron
accumulation is frequently noted in these diseases and compelling
evidence exists that iron is involved in inflammatory reactions.
Histochemical stains for iron repeatedly demonstrate that
oligodendrocytes, under normal conditions, stain more prominently than
any other cell type in the brain. Therefore, we examined the hypothesis
that cytokine toxicity to oligodendrocytes is iron mediated.
Oligodendrocytes in culture were exposed to interferon-gamma
(IFN-gamma), interleukin-1beta (IL-1beta), and tumor necrosis
factor-alpha (TNF-alpha). Toxicity was observed in a dose-dependent
manner for IFN-gamma and TNF-alpha. IL-1beta was not toxic in the
concentrations used in this study. The toxic concentration of
IFN-gamma, and TNF-alpha was lower if the cells were iron loaded, but
iron loading had no effect on the toxicity of IL-1beta. These data
provide insight into the controversy regarding the toxicity of
cytokines to oligodendrocytes by revealing that iron status of these
cells will significantly impact the outcome of cytokine treatment. The
exposure of oligodendrocytes to cytokines plus iron decreased
mitochondrial membrane potential but activation of caspase 3 is
limited. The antioxidant, TPPB, which targets mitochondria, protected
the oligodendrocytes from the iron-mediated cytotoxicity, providing
further support that mitochondrial dysfunction may underlie the
iron-mediated cytokine toxicity. Therapeutic strategies involving
anti-inflammatory agents have met with limited success in the treatment
of demyelinating disorders. A better understanding of these agents and
the contribution of cellular iron status to cytokine toxicity may help
develop a more consistent intervention strategy. (c) 2005 Wiley-Liss,
Inc.
PMID: 15968631 [PubMed - indexed for MEDLINE]
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