Rifampicin Prevents SH-SY5Y Cells from Rotenone-Induced Apoptosis via the PI3K/Akt/GSK-3β/CREB Signaling Pathway
Abstract
In addition to its original application for treating tuberculosis, rifampicin has multiple potential neuroprotective effects in chronic neurodegenerative diseases including Parkinson's disease (PD) and Alzheimer's disease. Inflammatory reactions and the PI3K/Akt pathway are strongly implicated in dopaminergic neuronal death in PD. This study aims to investigate whether rifampicin protects rotenone-lesioned SH-SY5Y cells via regulating PI3K/Akt/GSK-3β/CREB pathway. Rotenone-treated SH-SY5Y cells were used as the cell model to investigate the neuroprotective effects of rifampicin. Cell viability and apoptosis of SH-SY5Y cells were determined by CCK-8 assay and flow cytometry, respectively. The expression of Akt, p-Akt, GSK-3β, p-GSK-3β, CREB and p-CREB were measured by Western blot. Our results showed that the cell viability and level of phospho-CREB significantly decreased in SH-SY5Y cells exposed to rotenone when compared to the control group. Both the cell viability and the expression of phospho-CREB in cells pretreated with rifampicin were higher than those of cells exposed to rotenone alone. Moreover, pretreatment of SH-SY5Y cells with rifampicin enhanced phosphorylation of Akt and suppressed activity of GSK-3β. The addition of LY294002, a PI3K inhibitor, could suppress phosphorylation of Akt and CREB and activate GSK-3β, resulting in abolishment of neuroprotective effects of rifampicin on cells exposed to rotenone. Rifampicin provides neuroprotection against dopaminergic degeneration, partially via the PI3K/Akt/GSK-3β/CREB signaling pathway. These findings suggest that rifampicin could be an effective and promising neuroprotective candidate for treating PD.
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Rifampicin sustains cell viability via PI3K/Akt/GSK-3β/CREB pathway modulation.
“Although not completely defined, rifampicin appears to sustain cell viability through different mechanisms: (i) by enhancing autophagy [293,295]; (ii) via PI3K/Akt/GSK-3β/CREB pathway modulation [296]; (iii) by upregulating the unfolded protein response marker GRP78 through the PERK/eIF2α/ATF4 pathway [297].”
From The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment (2022) · cites this paper as [296]
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- Authors
- Wu, X., Liang, Y., Jing, X., Lin, D., Chen, Y., Zhou, T., Peng, S., Zheng, D., Zeng, Z., Lei, M., Huang, K., & Tao, E.
- Affiliations
- Sun Yat-sen University (CN)
- Corresponding author
- Tao, Enxiang
- Venue
- Neurochemical Research
- Published
- 2018-02-12
- Volume
- 43
- Issue
- 4
- Pages
- 886-893
- ISSN
- 0364-3190 (ISSN-L)
- 1573-6903
- OpenAlex
- W2793177201
- Cited by
- 55
- References
- 35
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 8 · 2023: 10 · 2022: 7 · 2021: 5 · 2020: 8 · 2019: 8 · 2018: 1
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neurochemical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81571244, 81503052, 81771378, 81371391)
- Public Welfare Research and Capacity Building Project of Guangdong Province (2014A020212164)
- Natural Science Foundation of Guangdong Province (2014A030313202, 2016A030313322, 2017A030313840)
- Guangzhou Science and Technology Research Project (201607010219)
- Fundamental Research Fund for University Youth Scholars (17ykpy39)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Keywords
- rifampicin, rotenone, apoptosis, neuroprotection, Parkinson's disease, dopaminergic neurons, SH-SY5Y cells, PI3K/Akt signaling, GSK3β, CREB, LY294002, neurodegeneration
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Phosphoinositide-3 Kinase Inhibitors, Cell Survival, Enzyme Inhibitors, Humans, Rifampin, Rotenone, Signal Transduction, Apoptosis, Cyclic AMP Response Element-Binding Protein, Phosphatidylinositol 3-Kinases, Cell Line, Tumor, Proto-Oncogene Proteins c-akt
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