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Celastrol attenuates 6-hydroxydopamine-induced neurotoxicity by regulating the miR-146a/PI3K/Akt/mTOR signaling pathways in differentiated rat pheochromocytoma cells
- Source :
- Journal of Affective Disorders. 316:233-242
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
Abstract
- Parkinson's disease (PD) is a neurological disorder. Recently, celastrol (Cel) has been reported to have neuroprotective properties. We investigated the protective effects of Cel on PD in a cell model with 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in PC12 cells and further addressed the underlying protective mechanisms of Cel.PC12 cells were treated with 6-OHDA, and Cel was added to the medium at various concentrations. The CCK-8 assay, Hoechst/PI staining, and flow cytometry analysis were performed to detect cellular viability and apoptosis. Mitochondrial membrane potential (MMP) was examined by JC-1 staining. ROS level was quantified by ROS staining. The effects of Cel on the expression of miR-146a and PI3K/Akt/mTOR pathway were then clarified using real-time PCR and Western blotting. Moreover, a miR-146a mimic was synthesized and transfected into PC12 cells to further determine the mechanisms of Cel's neuronal protection against 6-OHDA-induced neurotoxicity.Cel greatly improved cell viability and lessened apoptosis. Flow cytometry showed that Cel especially inhibited early apoptosis. Cel also obviously restored the MMP and decreased ROS level destroyed by 6-OHDA. Moreover, 6-OHDA increased the expression of miR-146a and decreased pAkt/mTOR protein levels, whereas Cel reversed these changes. In particular, miR-146a targeted and inhibited the expression of PI3K, an upstream molecule of Akt/mTOR. Transfection of 6-OHDA-treated neurons with miR-146a mimic notably attenuated Cel's protective effects.There were no animal experiments in our study.Cel exerts neuroprotective activity against 6-OHDA-caused neurotoxicity by regulating miR-146a/PI3K/Akt/mTOR pathway, which provides a potential application of Cel for treating neurodegenerative diseases.
- Subjects :
- TOR Serine-Threonine Kinases
Adrenal Gland Neoplasms
Apoptosis
Parkinson Disease
Pheochromocytoma
Rats
MicroRNAs
Phosphatidylinositol 3-Kinases
Psychiatry and Mental health
Clinical Psychology
Neuroprotective Agents
Animals
Oxidopamine
Pentacyclic Triterpenes
Reactive Oxygen Species
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 01650327
- Volume :
- 316
- Database :
- OpenAIRE
- Journal :
- Journal of Affective Disorders
- Accession number :
- edsair.doi.dedup.....422dff365fed50b5b7fff6053bd77ba4