Neuroprotective effects of salidroside against beta-amyloid-induced oxidative stress in SH-SY5Y human neuroblastoma cells.

Abstract

Beta-amyloid (Abeta) peptide, the hallmark of Alzheimer's disease (AD), invokes a cascade of oxidative damages to neurons and eventually leads to neuronal death. In this study, salidroside (Sald), an active compound isolated from a traditional Chinese medicinal plant, Rhodiola rosea L., was investigated to assess its protective effects and the underlying mechanisms against Abeta-induced oxidative stress in SH-SY5Y human neuroblastoma cells. Abeta(25-35)-induced neuronal toxicity was characterized by the decrease of cell viability, the release of lactate dehydrogenase (LDH), morphological alterations, neuronal DNA condensation, and the cleavage of poly(ADP-ribose) polymerase (PARP) by activated caspase-3. Pretreatment with salidroside markedly attenuated Abeta(25-35)-induced loss of cell viability and apoptosis in a dose-dependent manner. The mechanisms of salidroside protected neurons from oxidative stress included the induction of antioxidant enzymes, thioredoxin (Trx), heme oxygenase-1 (HO-1), and peroxiredoxin-I (PrxI); the downregulation of pro-apoptotic protein Bax and the upregulation of anti-apoptotic protein Bcl-X(L). Furthermore, salidroside dose-dependently restored Abeta(25-35)-induced loss of mitochondrial membrane potential (MMP) as well as suppressed the elevation of intracellular reactive oxygen species (ROS) level. It was also observed that Abeta(25-35) stimulated the phosphorylation of mitogen-activated protein (MAP) kinases, including c-Jun NH(2)-terminal kinase (JNK) and p38 MAP kinase, but not extracellular signal-regulated kinase1/2 (ERK1/2). Salidroside inhibited Abeta(25-35)-induced phosphorylation of JNK and p38 MAP kinase, but not ERK1/2. These results suggest that salidroside has protective effects against Abeta(25-35)-induced oxidative stress, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases.

• Authors: Li Zhang, Huixin Yu, Xincan Zhao, Xiufeng Lin, Chen Tan, Guoxian Cao, Zhengwu Wang
• Journal: Neurochemistry international (Neurochem Int) Vol. 57 Issue 5 Pg. 547-55 (Nov 2010) ISSN: 1872-9754 [Electronic] England
• PMID: 20615444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ltd. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• DNA Primers
• Glucosides
• Neuroprotective Agents
• Peptide Fragments
• Phenols
• RNA, Messenger
• Reactive Oxygen Species
• amyloid beta-protein (25-35)
• L-Lactate Dehydrogenase
• Heme Oxygenase-1
• p38 Mitogen-Activated Protein Kinases
• Trypan Blue
• Sincalide
• rhodioloside

Topics

• Amyloid beta-Peptides (antagonists & inhibitors, toxicity)
• Apoptosis (drug effects)
• Blotting, Western
• Cell Line, Tumor
• Cell Survival (drug effects)
• DNA Primers
• Flow Cytometry
• Glucosides (pharmacology)
• Heme Oxygenase-1 (biosynthesis)
• Humans
• L-Lactate Dehydrogenase (metabolism)
• Membrane Potentials (drug effects)
• Mitochondrial Membranes (drug effects)
• Neuroprotective Agents
• Oxidative Stress (drug effects)
• Peptide Fragments (antagonists & inhibitors, toxicity)
• Phenols (pharmacology)
• RNA, Messenger (biosynthesis, genetics)
• Reactive Oxygen Species (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Sincalide (metabolism)
• Trypan Blue
• p38 Mitogen-Activated Protein Kinases (metabolism)