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Effects of lysophosphatidylcholine on beta-amyloid-induced neuronal apoptosis.

ABSTRACT: AIM: We have investigated the effects of lysophosphatidylcholine (LPC), a product of lipid peroxidation, on Abeta(1-42)-induced SH-SY5Y cell apoptosis. METHODS: The viability of cultured SH-SY5Y cells was measured using a CCK-8 kit. Apoptosis was determined by Chip-based flow cytometric assay. The mRNA transcription of Bcl-2, Bax, and caspase-3 were detected by using reverse transcription and real-time quantitative PCR and the protein levels of Bax and caspase-3 were analyzed by Western blotting. The cytosolic calcium concentration of SH-SY5Y cells was tested by calcium influx assay. G2A expression in SH-SY5Y cells was silenced by small interfering RNA. RESULTS: Long-term exposure of SH-SY5Y cells to LPC augmented the neurotoxicity of Abeta(1-42). Furthermore, after LPC treatment, the Bax/Bcl-x(L) ratio and the expression levels, as well as the activity of caspase-3 were, elevated, whereas the expression level of TRAF1 was reduced. Because LPC was reported to be a specific ligand for the orphan G-protein coupled receptor, G2A, we investigated LPC-mediated changes in calcium levels in SH-SY5Y cells. Our results demonstrated that LPC can enhance the Abeta(1-42)-induced elevation of intracellular calcium. Interestingly, Abeta(1-42) significantly increased the expression of G2A in SH-SY5Y cells, whereas knockdown of G2A using siRNA reduced the effects of LPC on Abeta(1-42)-induced neurotoxicity. CONCLUSION: The effects of LPC on Abeta(1-42)-induced apoptosis may occur through the signal pathways of the orphan G-protein coupled receptor.

SUBMITTER: Qin ZX

PROVIDER: S-EPMC4002278 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Effects of lysophosphatidylcholine on beta-amyloid-induced neuronal apoptosis.

Qin Zhen-xia ZX Zhu Hui-yan HY Hu Ying-he YH

Acta pharmacologica Sinica 20090401 4

<h4>Aim</h4>We have investigated the effects of lysophosphatidylcholine (LPC), a product of lipid peroxidation, on Abeta(1-42)-induced SH-SY5Y cell apoptosis.<h4>Methods</h4>The viability of cultured SH-SY5Y cells was measured using a CCK-8 kit. Apoptosis was determined by Chip-based flow cytometric assay. The mRNA transcription of Bcl-2, Bax, and caspase-3 were detected by using reverse transcription and real-time quantitative PCR and the protein levels of Bax and caspase-3 were analyzed by Wes ...[more]

PMID: 19343059

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Project description:BackgroundDespite diverging levels of amyloid-β (Aβ) and TAU pathology, different mouse models, as well as sporadic AD patients show predictable patterns of episodic memory loss. MicroRNA (miRNA) deregulation is well established in AD brain but it is unclear whether Aβ or TAU pathology drives those alterations and whether miRNA changes contribute to cognitive decline.MethodsmiRNAseq was performed on cognitively intact (4 months) and impaired (10 months) male APPtg (APPswe/PS1L166P) and TAUtg (THY-Tau22) mice and their wild-type littermates (APPwt and TAUwt). We analyzed the hippocampi of 12 mice per experimental group (n = 96 in total), and employed a 2-way linear model to extract differentially expressed miRNAs. Results were confirmed by qPCR in a separate cohort of 4 M and 10 M APPtg and APPwt mice (n = 7-9 per group) and in human sporadic AD and non-demented control brain. Fluorescent in situ hybridization identified their cellular expression. Functional annotation of predicted targets was performed using GO enrichment. Behavior of wild-type mice was assessed after intracerebroventricular infusion of miRNA mimics.ResultsSix miRNAs (miR-10a-5p, miR-142a-5p, miR-146a-5p, miR-155-5p, miR-211-5p, miR-455-5p) are commonly upregulated between APPtg and TAUtg mice, and four of these (miR-142a-5p, miR-146a-5p, miR-155-5p and miR-455-5p) are altered in AD patients. All 6 miRNAs are strongly enriched in neurons. Upregulating these miRNAs in wild-type mice is however not causing AD-related cognitive disturbances.ConclusionDiverging AD-related neuropathologies induce common disturbances in the expression of neuronal miRNAs. 4 of these miRNAs are also upregulated in AD patients. Therefore these 4 miRNAs (miR-142a-5p, miR-146a-5p, miR-155-5p and miR-455-5p) appear part of a core pathological process in AD patients and APPtg and TAUtg mice. They are however not causing cognitive disturbances in wild-type mice. As some of these miRNA target AD relevant proteins, they may be, in contrast, part of a protective response in AD.

Dataset Information

Effects of lysophosphatidylcholine on beta-amyloid-induced neuronal apoptosis.

Publications

Effects of lysophosphatidylcholine on beta-amyloid-induced neuronal apoptosis.

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