title: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Qingdao University, Qingdao, Shandong Province, China. Electronic address: linhou@qdu.edu.cn.
authors.forename: Lin
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Neonatology, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Medical College of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Chuanxia
authors.initials: C
authors.lastname: Ju
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Experiment Center of Biochemistry and Molecular Biology, Medical College of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Experiment Center of Biochemistry and Molecular Biology, Medical College of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Laboratory Department of the Third People׳s Hospital of Qingdao, Qingdao, Shandong Province, China.
authors.forename: Cun
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical College of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Wang
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D009474:Neurons; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000473:pathology*; D010833:Phytic Acid / Q000494:pharmacology*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D018663:Adrenergic Agents; D018696:Neuroprotective Agents; D051844:alpha-Synuclein; D010833:Phytic Acid; D016627:Oxidopamine
keywords: Inositol hexaphosphate; Mitochondrion mediated apoptotic pathway; Parkinson׳s disease; α-synuclein aggregation