Paeoniflorin inhibition of 6-hydroxydopamine-induced apoptosis in PC12 cells via suppressing reactive oxygen species-mediated PKCδ/NF-κB pathway
| Autor: | X Zhang, Miaoxian Dong, H Dong, Tianjiao Xu, R Li, Chunlei Yu |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Programmed cell death
Cell Survival p38 mitogen-activated protein kinases Apoptosis Pharmacology medicine.disease_cause PC12 Cells Antioxidants chemistry.chemical_compound Cytosol Glucosides medicine Animals Oxidopamine Protein kinase B chemistry.chemical_classification Reactive oxygen species NADPH oxidase biology General Neuroscience NF-kappa B Cytochromes c NADPH Oxidases Paeoniflorin Molecular biology Rats Oxidative Stress Protein Kinase C-delta Neuroprotective Agents nervous system chemistry Monoterpenes biology.protein Reactive Oxygen Species Nicotinamide adenine dinucleotide phosphate Oxidative stress Signal Transduction |
| Zdroj: | Neuroscience. 285:70-80 |
| ISSN: | 0306-4522 |
| Popis: | Parkinson's disease (PD) is second only to Alzheimer's disease as the most common devastating human neurodegenerative disorder. Despite intense investigation, no curative therapy is available for PD. Paeoniflorin, a monoterpene glucoside isolated from the Paeonia lactiflora Pall., possesses wide pharmacological effects in the nervous system. This study aims at evaluating the effect of paeoniflorin on 6-hydroxydopamine (6-OHDA)-induced apoptosis and to characterize involved signal transduction pathways in PC12 cells. Our results showed that paeoniflorin suppresses mitochondria-mediated apoptosis of PC12 cells induced by 6-OHDA, and anti-apoptotic effects of paeoniflorin on PC12 cells might mainly result from its antioxidant capability by increasing glutathione (GSH). Moreover, we also found that paeoniflorin can dramatically attenuate the 6-OHDA-induced nuclear factor κB (NF-κB) translocation without affecting phosphorylation of Akt, JNK, p38, and ERK1/2. 6-OHDA-induced protein kinase Cδ (PKCδ) upregulation was blocked by paeoniflorin treatment in PC12 cells. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenyleneiodonium or NF-κB inhibitor BAY 11-7082 could partially attenuate 6-OHDA-induced cell death. Together, our results indicate that the inhibition of PC12 cell apoptosis by paeoniflorin might be mediated, at least in part, by inhibiting reactive oxygen species (ROS)/PKCδ/NF-κB signaling pathway. This evidence supports the pharmacological potential of paeoniflorin in the management of neurodegenerative disorders associated with oxidative stress, including PD. |
| Databáze: | OpenAIRE |
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