Dataset Information

Shikonin Protects PC12 Cells Against β-amyloid Peptide-Induced Cell Injury Through Antioxidant and Antiapoptotic Activities.

ABSTRACT: Excessive accumulation of β-amyloid (Aβ) is thought to be a major causative factor in the pathogenesis of Alzheimer's disease (AD). Pretreating Aβ-induced neurotoxicity is a potential therapeutic approach to ameliorate the progression and development of AD. The present study aimed to investigate the neuroprotective effect of shikonin, a naphthoquinone pigment isolated from the roots of the traditional Chinese herb Lithospermum erythrorhizon, on Aβ_1-42-treated neurotoxicity in PC12 cells. Pretreating cells with shikonin strongly improved cell viability, decreased the malondialdehyde and reactive oxygen species (ROS) content, and stabilized the mitochondrial membrane potential in Aβ_1-42-induced PC12 cells. In addition, shikonin strongly improved the response of the antioxidant system to ROS by increasing the levels of superoxidedismutase, catalase and glutathione peroxidase. Furthermore, shikonin has the ability to reduce proapoptotic signaling by reducing the activity of caspase-3 and moderating the ratio of Bcl-2/Bax. These observations indicate that shikonin holds great potential for neuroprotection via inhibition of oxidative stress and cell apoptosis.

SUBMITTER: Tong Y

PROVIDER: S-EPMC5758797 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Shikonin Protects PC12 Cells Against β-amyloid Peptide-Induced Cell Injury Through Antioxidant and Antiapoptotic Activities.

Tong Yuna Y Bai Lan L Gong Rong R Chuan Junlan J Duan Xingmei X Zhu Yuxuan Y

Scientific reports 20180108 1

Excessive accumulation of β-amyloid (Aβ) is thought to be a major causative factor in the pathogenesis of Alzheimer's disease (AD). Pretreating Aβ-induced neurotoxicity is a potential therapeutic approach to ameliorate the progression and development of AD. The present study aimed to investigate the neuroprotective effect of shikonin, a naphthoquinone pigment isolated from the roots of the traditional Chinese herb Lithospermum erythrorhizon, on Aβ<sub>1-42</sub>-treated neurotoxicity in PC12 cel ...[more]

PMID: 29311595

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Project description:Complement inhibitor C4b-binding protein (C4BP) is synthesized in liver and pancreas and composed of 7 identical alpha chains and one unique beta chain. We showed previously that C4BP binds islet amyloid polypeptide (IAPP) and affects fibril formation in vitro. Now we found that polymeric C4BP inhibited lysis of human erythrocytes incubated with monomeric IAPP while no erythrocyte lysis was observed after incubation with preformed IAPP fibrils. In contrast, monomeric alpha chain of C4BP had significantly reduced activity. Further, addition of monomeric IAPP to a rat insulinoma cell line (INS-1) resulted in decreased cell viability, which was restored in the presence of physiological concentrations of C4BP. Accordingly, addition of C4BP rescued the ability of INS-1 cells and isolated rat islets to respond to glucose stimulation with insulin secretion, which was impaired in the presence of IAPP alone. C4BP was internalized together with IAPP into INS-1 cells and therefore we aimed to study its effect on gene expression. Pathway analyses of mRNA expression microarray data indicated that cells exposed to C4BP and IAPP in comparison to IAPP alone increased expression of genes involved in cholesterol synthesis. Depletion of cholesterol through methyl-Î²-cyclodextrin or cholesterol oxidase abolished the protective effect of C4BP on IAPP cytotoxicity of INS-1 cells. Also, inhibition of phosphoinositide 3-kinase but not NF-ÎºB had a similar effect. Taken together, one of the mechanisms by which C4BP protects beta-cells from IAPP cytotoxicity is by enhancing cholesterol synthesis. The INS-1 cells were grown as 5 separate clones for 10 passages before plating in a 12-well plate (Nunc) at 100.000 cells per well and grown in complete RPMI 1640 medium to 70% confluency for approximately 48 h. The cells were then challenged by adding 77 Î¼M monomeric IAPP alone or together with C4BP (0.6 Î¼M). DMSO (1%) used as solvent for IAPP as well as C4BP (0.6 Î¼M) alone were used as controls. RNA was extracted after 10h incubation and analysis carried out using Rat Gene 2.0 array chip (Affymetrix).

Dataset Information

Shikonin Protects PC12 Cells Against β-amyloid Peptide-Induced Cell Injury Through Antioxidant and Antiapoptotic Activities.

Publications

Shikonin Protects PC12 Cells Against β-amyloid Peptide-Induced Cell Injury Through Antioxidant and Antiapoptotic Activities.

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