Glutathione Depletion in Immortalized Midbrain-derived Dopaminergic Neurons Results in Increases in the Labile Iron Pool: Implications for Parkinson's Disease

Overview

Journal Free Radic Biol Med

Specialties Biochemistry
Biology
General Medicine

Date 2009 Jan 3

PMID 19118623

Citations 17

Authors

Deepinder Kaur

Donna Lee

Subramanian Ragapolan

Julie K Andersen

Affiliations

Soon will be listed here.

Abstract

Glutathione depletion is one of the earliest detectable events in the Parkinsonian substantia nigra (SN), but whether it is causative for ensuing molecular events associated with the disease is unknown. Here we report that reduction in levels of glutathione in immortalized midbrain-derived dopaminergic neurons results in increases in the cellular labile iron pool (LIP). This increase is independent of either iron regulatory protein/iron regulatory element (IRP/IRE) or hypoxia inducible factor (HIF) induction but is both H(2)0(2) and protein synthesis-dependent. Our findings suggest a novel mechanistic link between dopaminergic glutathione depletion and increased iron levels based on translational activation of TfR1. This may have important implications for neurodegeneration associated with Parkinson's disease in which both glutathione reduction and iron elevation have been implicated.

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