Phytic Acid Protects against 6-Hydroxydopamine-Induced Dopaminergic Neuron Apoptosis in Normal and Iron Excess Conditions in a Cell Culture Model

Publication

Publication Type:

Journal Article

Source:

Parkinson's Disease, Volume 2011, Issue 7 (2011)

URL:

http://www.hindawi.com/journals/pd/2011/431068/

Abstract:

Iron metabolism is disrupted and excess iron accumulation was reported in the brains of Parkinson’s disease (PD) patients. Because excessive iron can promote oxidative stress and subsequent neuronal degeneration of nigral dopaminergic neurons in PD, we determined the protective effect of a naturally occurring iron chelator, phytic acid (IP6) on 6-hydroxydopamine (6-OHDA) induced cell death in immortalized rat mesencephalicdopaminergic cell model (N27 cells). Cells were grown with or without IP6 for 30h and the cell death was induced by 6-OHDA in the last 6h. For iron excess conditions, cells were grown with iron (50 µmol/L) for 30h and IP6 and 6-OHDA were added together in the last 6h. Apoptosis was measured by caspase-3 activity, DNA fragmentation, and Hoechst nuclear staining. Caspase-3 activity was significantly (p<0.001) increased by 6-fold with 6-OHDA compared to the control group and 30 µmol/L IP6 pretreatment decreased it by 38% (p<0.05). Similar results were obtained in iron excess condition. The 3-fold enhancement (p<0.01) of DNA fragmentation with 6-OHDA was significantly (p<0.01) reduced by 58% with IP6. Although the DNA damage was less pronounced in iron excess condition, IP6 treatment counteracted that effect. In addition, Hoechst nuclear staining results confirmed the protective effect of IP6 against apoptosis. Our results showing the protective effect of on 6-OHDA-induced cell apoptosis in both normal and iron excess conditions suggest the potential use of IP6 in preventing the progression of PD treatment.