NQO1 regulates expression and alternative splicing of apoptotic genes associated with Alzheimer's disease in PC-12 cells
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ABSTRACT:
PROVIDER: PRJNA770248 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16288682_1.fastq.gz | Fastqsanger.gz | |||
| SRR16288682_2.fastq.gz | Fastqsanger.gz | |||
| SRR16288683_1.fastq.gz | Fastqsanger.gz | |||
| SRR16288683_2.fastq.gz | Fastqsanger.gz | |||
| SRR16288684_1.fastq.gz | Fastqsanger.gz |
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Project description:Quinone oxidoreductase I (NQO1), an important antioxidant enzyme which plays an important role in monitoring cellular redox state, was altered in the brain tissues of Alzheimer’s disease (AD) patients. In addition to its traditional antioxidant effect, NQO1 is also a multifunctional RNA-binding protein (RBP) in post-transcriptional regulation. However, NQO1 in AD pathology by acting as an RBP is not studied. In the present study, the RBP functions of NQO1 in rat PC12 cells, a cell line widely used in neurological disease studies, were investigated using siRNA knock-down (KD) and following whole transcriptome (RNA-seq) analysis. Reduced levels of NQO1 led to a significant increase in cellular apoptosis, compared with control cells. Notably, RNA-seq analysis of the transcriptome of PC12 cells by NQO1-KD revealed that genes in certain apoptosis pathways, were under global transcriptional and alternative splicing regulation. Quantitative RT-PCR confirmed the NQO1-regulated transcription of apoptotic genes Cryab, Lgmn , Ngf, Apoe, Brd7, Stat3, and alternative splicing of Bin1, Picalm, Fyn. These NQO1-regulated genes have been found to be closely related to AD pathogenesis. Our findings suggest that NQO1 acts as an RBP and participates in the pathology of AD by regulating expression and alternative splicing of genes involved in apoptosis. The results of present study extend our understanding of the cellular and molecular mechanisms in AD pathogenesis, which might contribute to the development of novel therapeutic targets.
2023-10-20 | GSE185633 | GEO
Project description:We analysed changes in transcript levels and alternative splicing in the temporal cortex of individuals of different ages that were cognitively normal, affected by frontotemporal lobar degeneration (FTLD), or affected by Alzheimer's disease (AD). Our experiment's purpose is to provide new insights into the gene expression changes that distinguish healthy aging from neurodegeneration and identify the candidate regulators of alternative splicing that are associated with both processes.
2012-04-27 | E-MTAB-656 | biostudies-arrayexpress
Project description:Alternative splicing is a mechanism for increasing the protein variety of a limited number of genes. Studies have shown that aberrant regulations of the alternative splicing of apoptotic gene transcripts may contribute to the development of cancer. In this study, we isolated 4β-Hydroxywithanolide E (4bHWE) from the traditional herb Physalis peruviana, and analyzed its biological effects in cancer cells. The results demonstrated that 4bHWE modulates the alternative splicing of apoptotic genes (e.g., HIPK3, SMAC/DIABLO, and SURVIVIN), changes the expression level of splicing factors (e.g., hnRNP C1/C2, ASF/SF2, SRp20, and SRp55), and induces histone tail posttranslational modifications (e.g., H3K27me1, H3K27me2, H3K36me3, and H3K79me1). Pretreatment with okadaic acid to inhibit protein phosphatase-1 could partly relieve the effects of 4bHWE on the alternative splicing of HIPK3 and SMAC/DIABLO transcripts, as well as on the dephosphorylation of ASF/SF2. Genome-wide detection of alternative splicing further indicated that several other apoptosis-related genes are also regulated by 4bHWE, including APAF1, CARP-1, and RIPK1. Moreover, we extended our study to apoptosis-associated molecules, detecting an increasing level of CASPASE-3 activity and cleavage of poly ADP-ribose polymerase in 4bHWE-induced apoptosis. Furthermore, in vivo experiments showed that the treatment of tumor-bearing mice with 4bHWE resulted in a marked decrease of tumor size and weight. Taken together, this study is the first to show that 4bHWE affects alternative splicing through the modulations of splicing factors, providing a novel view of the antitumor mechanism of 4bHWE.
2017-08-18 | GSE79884 | GEO
Project description:Natural antibodies, which arise without known immune exposure, have been described that specifically recognize cells dying from apoptosis but their role in innate immunity remains poorly understood. Herein, we show that the immune response to neo-antigenic determinants on apoptotic thymocytes is dominated by antibodies to oxidation-associated antigens, phosphorylcholine (PC), a head group that becomes exposed during programmed-cell death, and malondialdehyde (MDA), a reactive aldehyde degradation product of polyunsaturated lipids produced following exposure to reactive-oxidation species. While natural antibodies to apoptotic cells in naïve adult mice were dominated by PC and MDA specificities, the amounts of these antibodies were substantially boosted by treatment of mice with apoptotic cells. Moreover, the relative amounts of PC and MDA antibodies was affected by VH gene inheritance. Antibody interactions with apoptotic-cells also mediated the recruitment of C1q, which alone can promote apoptotic-cell phagocytosis by immature dendritic cells. Significantly, IgM-antibodies to both PC and MDA were primary factors in determining the efficiency of serum-dependent apoptotic-cell phagocytosis. Hence, we demonstrate a mechanism by which certain natural antibodies that recognize neo-antigens on apoptotic cells, in naïve mice and those induced by immune exposure to apoptotic-cells, can enhance the functional capabilities of immature dendritic cells for phagocytic engulfment of apoptotic cells. Keywords: Natural antibodies, Inflammation, Complement, Apoptosis
2009-02-23 | GSE14958 | GEO
Project description:Natural antibodies, which arise without known immune exposure, have been described that specifically recognize cells dying from apoptosis but their role in innate immunity remains poorly understood. Herein, we show that the immune response to neo-antigenic determinants on apoptotic thymocytes is dominated by antibodies to oxidation-associated antigens, phosphorylcholine (PC), a head group that becomes exposed during programmed-cell death, and malondialdehyde (MDA), a reactive aldehyde degradation product of polyunsaturated lipids produced following exposure to reactive-oxidation species. While natural antibodies to apoptotic cells in naM-CM-/ve adult mice were dominated by PC and MDA specificities, the amounts of these antibodies were substantially boosted by treatment of mice with apoptotic cells. Moreover, the relative amounts of PC and MDA antibodies was affected by VH gene inheritance. Antibody interactions with apoptotic-cells also mediated the recruitment of C1q, which alone can promote apoptotic-cell phagocytosis by immature dendritic cells. Significantly, IgM-antibodies to both PC and MDA were primary factors in determining the efficiency of serum-dependent apoptotic-cell phagocytosis. Hence, we demonstrate a mechanism by which certain natural antibodies that recognize neo-antigens on apoptotic cells, in naM-CM-/ve mice and those induced by immune exposure to apoptotic-cells, can enhance the functional capabilities of immature dendritic cells for phagocytic engulfment of apoptotic cells. Keywords: Natural antibodies, Inflammation, Complement, Apoptosis In the study presented here, a total of 11 custom-spotted protein slides were hybridized with a T15 IgM monoclonal antibody at three different concentrations, an isotype control IgM, 2 slides were hybridized with serum from naM-QM-^Wve mice, 2 slides incubated with serum from mice immunized with apoptotic cells, 2 slides were incubated with serum from mice immunized with saline, and a negative control slide with no antibody hybridized
2009-02-23 | E-GEOD-14958 | biostudies-arrayexpress
Project description:PurposeAlzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory loss and cognitive dysfunction. Quinone oxidoreductase 1 (NQO1) is an antioxidant enzyme that plays an important role in controlling cellular redox state, whose expression is altered in the brain tissues of AD patients. In addition to its traditional antioxidant effects, NQO1 also acts as a multifunctional RNA-binding protein involved in posttranscriptional regulation. Whether the RNA-binding activity of NQO1 influences AD pathology has not been investigated yet.MethodsThe RNA-binding functions of NQO1 in rat pheochromocytoma (PC12) cells were investigated using siRNA knockdown followed by total RNA sequencing. Reverse transcription quantitative polymerase chain reaction was performed to explore the impact of NQO1 on the transcription and alternative splicing of apoptotic genes.ResultsNQO1 knockdown led to a significant increase in cellular apoptosis. Genes involved in certain apoptosis pathways, such as positive regulation of apoptotic processes and mitogen-activated protein kinase signaling, were under global transcriptional and alternative splicing regulation. NQO1 regulated the transcription of apoptotic genes Cryab, Lgmn, Ngf, Apoe, Brd7, and Stat3, as well as the alternative splicing of apoptotic genes BIN1, Picalm, and Fyn.ConclusionOur findings suggest that NQO1 participates in the pathology of AD by regulating the expression and alternative splicing of the genes involved in apoptosis. These results extend our understanding of NQO1 in apoptotic pathways at the posttranscriptional level in AD.
| S-EPMC10175992 | biostudies-literature
Project description:Morganella morganii subsp. morganii PC strain:PC Genome sequencing
| PRJNA175476 | ENA
Project description:Ion channel splice array data from cerebellum brain tissue samples collected from Alzheimer's disease patients. Temporal cortex (Alzheimer's disease affected brain tissue structure) and cerebellum (Alzheimer's disease unaffected brain tissue structure) samples from control subjects were compared to temporal cortex and cerebellum of patients with Alzheimer's disease.
2010-06-11 | E-GEOD-6777 | biostudies-arrayexpress
Project description:Ion channel splice array data from temporal cortex brain tissue samples collected from Alzheimer's disease patients. Temporal cortex (Alzheimer's disease affected brain tissue structure) and cerebellum (Alzheimer's disease unaffected brain tissue structure) samples from control subjects were compared to temporal cortex and cerebellum of patients with Alzheimer's disease.
2010-06-11 | E-GEOD-6775 | biostudies-arrayexpress
Project description:Ion channel splice array data from cerebellum brain tissue samples collected from control (non Alzheimer's disease) subjects. Temporal cortex (Alzheimer's disease affected brain tissue structure) and cerebellum (Alzheimer's disease unaffected brain tissue structure) samples from control subjects were compared to temporal cortex and cerebellum of patients with Alzheimer's disease.
2010-06-11 | E-GEOD-6778 | biostudies-arrayexpress