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Tau protein modulates an epigenetic mechanism of cellular senescence in human SH-SY5Y neuroblastoma cells.

ABSTRACT: Introduction: Progressive Tau deposition in neurofibrillary tangles and neuropil threads is the hallmark of tauopathies, a disorder group that includes Alzheimer's disease. Since Tau is a microtubule-associated protein, a prevalent concept to explain the pathogenesis of tauopathies is that abnormal Tau modification contributes to dissociation from microtubules, assembly into multimeric β-sheets, proteotoxicity, neuronal dysfunction and cell loss. Tau also localizes in the cell nucleus and evidence supports an emerging function of Tau in DNA stability and epigenetic modulation. Methods: To better characterize the possible role of Tau in regulation of chromatin compaction and subsequent gene expression, we performed a bioinformatics analysis of transcriptome data obtained from Tau-depleted human neuroblastoma cells. Results: Among the transcripts deregulated in a Tau-dependent manner, we found an enrichment of target genes for the polycomb repressive complex 2. We further describe decreased cellular amounts of the core components of the polycomb repressive complex 2 and lower histone 3 trimethylation in Tau deficient cells. Among the de-repressed polycomb repressive complex 2 target gene products, IGFBP3 protein was found to be linked to increased senescence induction in Tau-deficient cells. Discussion: Our findings propose a mechanism for Tau-dependent epigenetic modulation of cell senescence, a key event in pathologic aging.

SUBMITTER: Magrin C

PROVIDER: S-EPMC10569482 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Tau protein modulates an epigenetic mechanism of cellular senescence in human SH-SY5Y neuroblastoma cells.

Magrin Claudia C Bellafante Martina M Sola Martina M Piovesana Ester E Bolis Marco M Cascione Luciano L Napoli Sara S Rinaldi Andrea A Papin Stéphanie S Paganetti Paolo P

Frontiers in cell and developmental biology 20231003

<b>Introduction:</b> Progressive Tau deposition in neurofibrillary tangles and neuropil threads is the hallmark of tauopathies, a disorder group that includes Alzheimer's disease. Since Tau is a microtubule-associated protein, a prevalent concept to explain the pathogenesis of tauopathies is that abnormal Tau modification contributes to dissociation from microtubules, assembly into multimeric β-sheets, proteotoxicity, neuronal dysfunction and cell loss. Tau also localizes in the cell nucleus and ...[more]

PMID: 37842084

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Project description:Toxoplasma rhoptry protein 16 (ROP16) is crucial in the host-pathogen interaction by acting as a virulent factor during invasion. To improve understanding of the molecular function underlying the effect of ROP16 on host cells, the present study analyzed the transcriptional profile of genes in the ROP16‑transfected SH‑SY5Y human neuroblastoma cell line. The transcriptional profile of the SH‑SY5Y human neuroblastoma cell line overexpressing ROP16 were determined by microarray analysis in order to determine the host neural cell response to the virulent factor. Functional analysis was performed using the Protein Analysis Through Evolutionary Relationships classification system. The ToppGene Suite was used to select candidate genes from the differentially expressed genes. A protein‑protein interaction network was constructed using Cytoscape software according to the interaction associations determined using the Search Tool for the Retrieval of Interacting Genes/Proteins. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis of the selected genes confirmed the results of the microarray. The results showed that 383 genes were differentially expressed in response to ROP16 transfection, of which 138 genes were upregulated and 245 genes were downregulated. Functional analysis indicated that the differentially expressed genes (DEGs) were involved in several biological processes, including developmental process, biological regulation and apoptotic process. A total of 15 candidate genes from the DEGs were screened using the ToppGene Suite. No significant differences in expression were observed between the RT‑qPCR data and the microarray data. Transfection with ROP16 resulted in alterations of several biological processes, including nervous system development, apoptosis and transcriptional regulation. Several genes, including CXCL12, BAI1, ZIC2, RBMX, RASSF6, MAGE‑A6 and HOX, were identified as significant DEGs. Taken together, these results may contribute to understanding the mechanisms underlying the functions of ROP16 and provide scope for further investigation of the pathogenesis of Toxoplasma gondii.

Dataset Information

Tau protein modulates an epigenetic mechanism of cellular senescence in human SH-SY5Y neuroblastoma cells.

Publications

Tau protein modulates an epigenetic mechanism of cellular senescence in human SH-SY5Y neuroblastoma cells.

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