Sodium butyrate attenuates rotenone-induced toxicity by activation of autophagy through epigenetically regulating PGC-1α expression in PC12 cells
Abstract
Short-chain fatty acids (SCFAs) are considered the key molecular link between gut microbiota and pathogenesis of Parkinson's disease (PD). However, the role of SCFAs in PD pathogenesis is controversial. Autophagy is important for the degradation of α-synuclein, which is critical to the development of PD. However, whether SCFAs can regulate autophagy in PD remains unknown. We aimed to investigate the role of SCFAs and explore the potential mechanisms in rat dopaminergic PC12 cells treated with rotenone. Expression levels of α-synuclein, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and microtubule-associated protein 1 light chain 3 beta (LC3B)-II were detected by Western blot. Histone acetylation levels at PGC-1α promoter region were measured using chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR). Among the three SCFAs, sodium butyrate (NaB) protected against rotenone-induced toxicity. NaB activated autophagy pathway and reduced rotenone-induced α-synuclein expression through the activation of autophagy. Notably, NaB activated autophagy pathway through upregulating PGC-1α expression. More importantly, NaB promoted the levels of histone 3 lysine 9 acetylation (H3K9Ac) and histone 3 lysine 27 acetylation (H3K27Ac) at PGC-1α promoter region, indicating that NaB promotes PGC-1α expression via histone acetylation modification. In conclusion, NaB can protect against rotenone-induced toxicity through activation of the autophagy pathway by upregulating PGC-1α expression via epigenetic modification.
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Sodium butyrate exerts anti-apoptotic, anti-inflammatory, and neuroprotective effects on mice with Parkinson's disease.
“Notably, NaB exerts anti-apoptotic, anti-inflammatory, and neuroprotective effects on mice with PD [36,37,38]”
From Neuroprotective Effects of Sodium Butyrate by Restoring Gut Microbiota and Inhibiting TLR4 Signaling in Mice with MPTP-Induced Parkinson’s Disease (2023) · cites this paper as [38]
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- Authors
- Zhang, Y., Xu, S., Qian, Y., He, X., Mo, C., Yang, X., & Xiao, Q.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Yang, Xiaodong
- Xiao, Qin
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2022-02
- Volume
- 1776
- Pages
- 147749
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W4200391200
- Cited by
- 34
- References
- 57
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 13 · 2022: 2
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81801254, 81870998, 81901283)
- Special Project for Research and Development in Key areas of Guangdong Province (2018B030337001)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- sodium butyrate, rotenone, Parkinson's disease, autophagy, PGC-1α, short-chain fatty acids, histone acetylation, epigenetic regulation, alpha-synuclein, LC3B, gut microbiota
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Autophagy, Cell Survival, Rotenone, PC12 Cells, Butyric Acid, Epigenesis, Genetic, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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