Longevity-Associated Variant of BPIFB4 Confers Neuroprotection in the STHdh Cell Model of Huntington Disease
Abstract
:1. Introduction
2. Results
2.1. BPIFB4 Isoforms Confer Resistance to Nucleolar Stress
2.2. BPIFB4 Isoforms Decrease DNA Damage
2.3. BPIFB4 Isoforms Partially Preserve Cellular Identity
2.4. LAV-BPIFB4 Isoform Protects against Apoptosis through the Deregulation of Caspase Cascade
2.5. BPIFB4 Isoforms Decrease the Level of Trimethylated Histone 3 on Lysine 9 and Remodel Chromatin
- Nucleolar stress trigged by NCL sequestration in CAG RNA foci
- DNA damage and DNA repair dysfunction
- Caspase 3-dependent cell-death pathway
- H3K9me3-dependent heterochromatin condensation
- Decreases nucleolar stress
- Counteracts DNA damage and enhances DNA repair efficiency
- Inhibits the cleavage of pro-caspase 3, counteracting cell death in favor of cell viability
- Reduces the level of H3K9me3 through the ubiquitin–proteasome system
3. Discussion
3.1. LAV-BPIFB4 Counteracts the Nucleolar Stress
3.2. LAV-BPIFB4 Protects HD Neuron-like Cells from DNA Damage and Apoptosis via Inhibition of Caspase Signaling
3.3. BPIFB4 Isoforms Partially Counteract Neuronal Differentiation
3.4. BPIFB4 Reduces the Level of H3K9me3 in HD Neuron-like Cells
4. Material and Methods
4.1. Cell Maintenance, Treatment, and Differentiation
4.2. RNA Extraction and Quantitative Real-Time Analysis
4.3. Western Blotting
4.4. Immunofluorescence
4.5. Cell Viability
4.6. Comet Assay
4.7. Detection of Apoptosis by Flow-Cytometry
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Cattaneo, M.; Maciag, A.; Milella, M.S.; Ciaglia, E.; Bruno, A.; Puca, A.A. Longevity-Associated Variant of BPIFB4 Confers Neuroprotection in the STHdh Cell Model of Huntington Disease. Int. J. Mol. Sci. 2022, 23, 15313. https://doi.org/10.3390/ijms232315313
Cattaneo M, Maciag A, Milella MS, Ciaglia E, Bruno A, Puca AA. Longevity-Associated Variant of BPIFB4 Confers Neuroprotection in the STHdh Cell Model of Huntington Disease. International Journal of Molecular Sciences. 2022; 23(23):15313. https://doi.org/10.3390/ijms232315313
Chicago/Turabian StyleCattaneo, Monica, Anna Maciag, Maria Serena Milella, Elena Ciaglia, Antonino Bruno, and Annibale Alessandro Puca. 2022. "Longevity-Associated Variant of BPIFB4 Confers Neuroprotection in the STHdh Cell Model of Huntington Disease" International Journal of Molecular Sciences 23, no. 23: 15313. https://doi.org/10.3390/ijms232315313