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Eclalbasaponin I causes mitophagy to repress oxidative stress-induced apoptosis via activation of p38 and ERK in SH-SY5Y cells.
- Source :
-
Free radical research [Free Radic Res] 2019 Jun; Vol. 53 (6), pp. 655-668. Date of Electronic Publication: 2019 Jun 11. - Publication Year :
- 2019
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Abstract
- Oxidative stress accompanying excessive accumulation of reactive oxygen species (ROS) and mitochondrial dysfunction leads to the occurrence of neurodegenerative diseases. Our previous study showed that Eclalbasaponin I (EcI), a triterpene saponin isolated from Aralia elata (Miq.) Seem. ( A. elata ), repressed oxidative stress in human neuroblastoma SH-SY5Y cells. However, the detailed mechanism remains unclear. In this study, pretreatment with EcI in SH-SY5Y cells significantly activated the p38-mitogenactivated protein kinase (p38), the extracellular regulated protein kinase (ERK), whereas it did not affect the c-jun NH2 terminal kinases (JNK). In accordance with the initial findings, EcI-induced neuroprotective effect was attenuated by SB203580 (SB, a p38 inhibitor) or FR180204 (FR, an ERK inhibitor), being further confirmed by specific small interfering RNA (siRNA). Inhibition of either p38 or ERK up-regulated the apoptosis induction in EcI- and H <subscript>2</subscript> O <subscript>2</subscript> -cotreated cells. Furthermore, p38 or ERK suppression enhanced intracellular and mitochondrial ROS generation, decreased the activities of endogenous antioxidant defences as well as the mitochondrial membrane potential (MMP), resulting in dysfunction of mitochondria. In addition, EcI-induced autophagy and mitophagy were obviously down-regulated when p38 or ERK activation was blocked. Cumulatively, these findings supported that EcI-caused mitophagy contributed to the neuroprotective effect through p38 or ERK activation. Mitophagy induction might be an effective therapeutic intervention in neurodegenerative diseases.
- Subjects :
- Aralia chemistry
Cell Survival drug effects
Enzyme Activation drug effects
Humans
Hydrogen Peroxide antagonists & inhibitors
Hydrogen Peroxide pharmacology
Imidazoles pharmacology
Models, Molecular
Molecular Conformation
Neuroprotective Agents chemistry
Neuroprotective Agents isolation & purification
Protein Kinase Inhibitors pharmacology
Pyrazoles pharmacology
Pyridazines pharmacology
Pyridines pharmacology
Saponins chemistry
Saponins isolation & purification
Tumor Cells, Cultured
Apoptosis drug effects
Extracellular Signal-Regulated MAP Kinases metabolism
Mitophagy drug effects
Neuroprotective Agents pharmacology
Oxidative Stress drug effects
Saponins pharmacology
p38 Mitogen-Activated Protein Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1029-2470
- Volume :
- 53
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Free radical research
- Publication Type :
- Academic Journal
- Accession number :
- 31185752
- Full Text :
- https://doi.org/10.1080/10715762.2019.1620937