Neuroprotection of inositol hexaphosphate and changes of mitochondrion mediated apoptotic pathway and α-synuclein aggregation in 6-OHDA induced parkinson's disease cell model.

Abstract:

:Animal and cell experiments showed that inositol hexaphosphate (IP6) was protective on neurons in parkinson's disease (PD) model, but the underlying mechanism of this action was not extensively elucidated. To address this question, we established 6-hydroxydopamine (6-OHDA) induced human dopaminergic cell line SH-SY5Y as PD cell model and testified the neuroprotection of IP6. Through hoechst nuclear stain method and flow cytometric analysis, apoptosis induced by 6-OHDA was blocked by IP6 pretreatment. Significant protection against reactive oxygen species (ROS) and lipid peroxidation product malondialdehyde (MDA) was observed in 6-OHDA induced cells pretreated with IP6. To further investigate the mechanism of anti-apoptotic effect of IP6, expression of mediators in mitochondrion dependent apoptotic pathway was detected. Results indicated that loss of mitochondrial membrane potential, cytochrome c releasing, upregulation of Bcl-2-associated X protein (Bax), downregulation of B-cell CLL/lymphoma 2 (Bcl-2) and caspases activation were reversed by IP6. In addition, using flow cytometric method and western blot approach, our data showed that IP6 attenuated the rise of calcium and α-synuclein aggregation in cytosol. Collectively, IP6 exerted its neuroprotection on dopaminergic cells in PD cell model and the mechanism may be associated with changes of mitochondrion mediated apoptotic pathway and α-synuclein aggregation.

journal_name

Brain Res

journal_title

Brain research

authors

Zhang Z,Hou L,Li X,Ju C,Zhang J,Li X,Wang X,Liu C,Lv Y,Wang Y

doi

10.1016/j.brainres.2015.12.035

subject

Has Abstract

pub_date

2016-02-15 00:00:00

pages

87-95

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(15)00974-9

journal_volume

1633

pub_type

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