ArticlePloS one2014
Rifampicin protects PC12 cells from rotenone-induced cytotoxicity by activating GRP78 via PERK-eIF2α-ATF4 pathway.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Review
- From dysbiosis to dysfunction: specific gut microbes and metabolites in the pathogenesis of Parkinson's disease.Sustainable microbiology · 2026Review
- Pathophysiological Mechanisms Fostering Developmental and Epileptic Encephalopathies (DEE): a Complex Interplay between Genetics, Inflammation and Neurodegeneration.Current neurology and neuroscience reports · 2025Review
- Inhibition of pro-apoptotic UPR pathways PERK/CHOP and IRE1/JNK protects differentiated SH-SY5Y cells against rotenone-induced toxicity.Frontiers in molecular neuroscience · 2025Article
- Review
- Modulating Stress Proteins in Response to Therapeutic Interventions for Parkinson's Disease.International journal of molecular sciences · 2023Review
- The Interplay between Gut Microbiota and Parkinson's Disease: Implications on Diagnosis and Treatment.International journal of molecular sciences · 2022Review
- Omarigliptin Mitigates 6-Hydroxydopamine- or Rotenone-Induced Oxidative Toxicity in PC12 Cells by Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Actions.Antioxidants (Basel, Switzerland) · 2022Article
- Involvement of endoplasmic reticulum stress in rifampicin-induced liver injury.Frontiers in pharmacology · 2022Review
- Highly Potent, Selective, and Competitive Indole-Based MAO-B Inhibitors Protect PC12 Cells against 6-Hydroxydopamine- and Rotenone-Induced Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Article
- New Avenues for Parkinson's Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota.Biomolecules · 2021Review
- β-Asarone Regulates ER Stress and Autophagy Via Inhibition of the PERK/CHOP/Bcl-2/Beclin-1 Pathway in 6-OHDA-Induced Parkinsonian Rats.Neurochemical research · 2019Article
- GRP78/BIP/HSPA5 as a Therapeutic Target in Models of Parkinson's Disease: A Mini Review.Advances in pharmacological sciences · 2019Review
- Rifampicin Prevents SH-SY5Y Cells from Rotenone-Induced Apoptosis via the PI3K/Akt/GSK-3β/CREB Signaling Pathway.Neurochemical research · 2018Article
- Cellular and Molecular Basis of Neurodegeneration in Parkinson Disease.Frontiers in aging neuroscience · 2018Review
- Downregulation of Smac attenuates H2O2-induced apoptosis via endoplasmic reticulum stress in human lens epithelial cells.Medicine · 2017Article
- Neurotoxin mechanisms and processes relevant to Parkinson's disease: an update.Neurotoxicity research · 2015Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rifampicin has been proposed as a therapeutic candidate for Parkinson's disease (PD). We previously showed that rifampicin was neuroprotective in PD models in vivo and in vitro. However, the molecular mechanisms underlying are not fully elucidated. In this study, using the comprehensive proteomic analysis, we identified that the 78 kDa glucose-regulated protein (GRP78), a hallmark of the unfolded protein response (UPR), was upregulated in rifampicin-treated PC12 cells. Western blot analysis confirmed GRP78 activation. GRP78 functions cytoprotectively in stressed cells, therefore, we hypothesized that GRP78 mediated rifampicin-induced neuroprotection. Using RNA interference, we found that GRP78 gene knockdown significantly attenuated the neuroprotective effects of rifampicin. Next, we examined three UPR transducers, namely, protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol requiring kinase α (IREα) and activating transcription factor 6 (ATF 6), and how they regulated rifampicin-stimulated GRP78 expression. Our results showed that PERK, eukaryotic initiation factor 2α (eIF2α), and activating transcription factor 4 (ATF4) were activated in rifampicin-treated PC12 cells. Silencing the ATF4 gene using RNAi inhibited GRP78 stimulation. Interestingly, we did not detect significant IREα activation, X-box binding protein 1 mRNA splicing, or ATF6 cleavage up to 24 h after rifampicin treatment. Taken together, our data suggested that rifampicin induced GRP78 via the PERK-eIF2α-ATF4 pathway to protect neurons against rotenone-induced cell damage. Targeting molecules in this pathway could be a novel therapeutic approach for PD treatment.
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