Deferoxamine attenuates iron-induced oxidative stress and prevents mitochondrial aggregation and alpha-synuclein translocation in SK-N-SH cells in culture.
One of the defining characteristics of neurodegenerative diseases, including Parkinson's disease, is an abnormal accumulation of iron in the affected brain areas. By using SK-N-SH, a dopaminergic cell line, we have found that iron (100-250 microM FeSO(4)) decreased cell viability, increased lipid peroxidation, and the said effects were blocked by deferoxamine (DFO: 10 microM). Furthermore, DFO, in the absence of iron, enhanced the level of adenosine triphosphate (ATP), but caused chromatin condensation and cell death. Morphological studies revealed that iron (50-100 microM) altered mitochondrial morphology, disrupted nuclear membrane, and translocated alpha-synuclein from perinuclear region into the disrupted nucleus. The results of these studies suggest that DFO is able to block and attenuate iron-mediated oxidative stress. However, in the absence of excess iron, DFO itself may have deleterious effects on the morphology and hence integrity of dopaminergic neurons.
Sangchot
P
P
Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, N.D. 58203, USA.
Sharma
S
S
Chetsawang
B
B
Porter
J
J
Govitrapong
P
P
Ebadi
M
M
D000255:Adenosine Triphosphate / Q000032:analysis; D002470:Cell Survival / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology*; D005290:Ferric Compounds / Q000037:antagonists & inhibitors / Q000633:toxicity*; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051843:Synucleins; D014407:Tumor Cells, Cultured; D051844:alpha-Synuclein
D005290:Ferric Compounds; D007502:Iron Chelating Agents; D009419:Nerve Tissue Proteins; C497604:SNCA protein, human; D051843:Synucleins; D051844:alpha-Synuclein; C024823:ferric sulfate; D000255:Adenosine Triphosphate; D003676:Deferoxamine