title: Artemisinin protects PC12 cells against β-amyloid-induced apoptosis through activation of the ERK1/2 signaling pathway.
abstract: Accumulating evidence displays that an abnormal deposition of amyloid beta-peptide (Aβ) is the primary cause of the pathogenesis of Alzheimer's disease (AD). And therefore the elimination of Aβ is regarded as an important strategy for AD treatment. The discovery of drug candidates using culture neuronal cells against Aβ peptide toxicity is believed to be an effective approach to develop drug for the treatment of AD patients. We have previously showed that artemisinin, a FDA-approved anti-malaria drug, has neuroprotective effects recently. In the present study, we aimed to investigate the effects and potential mechanism of artemisinin in protecting neuronal PC12 cells from toxicity of β amyloid peptide. Our studies revealed that artemisinin, in clinical relevant concentration, protected and rescued PC12 cells from Aβ25-35-induced cell death. Further study showed that artemisinin significantly ameliorated cell death due to Aβ25-35 insult by restoring abnormal changes in nuclear morphology, lactate dehydrogenase, intracellular ROS, mitochondrial membrane potential and activity of apoptotic caspase. Western blotting analysis demonstrated that artemisinin activated extracellular regulated kinase ERK1/2 but not Akt survival signaling. Consistent with the role of ERK1/2, preincubation of cells with ERK1/2 pathway inhibitor PD98059 blocked the effect of artemisinin while PI3K inhibitor LY294002 has no effect. Moreover, Aβ1-42 also caused cells death of PC12 cells while artemisinin suppressed Aβ1-42 cytotoxicity in PC12 cells. Taken together, these results, at the first time, suggest that artemisinin is a potential protectant against β amyloid insult through activation of the ERK1/2 pathway. Our finding provides a potential application of artemisinin in prevention and treatment of AD.
authors.affiliation: Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
authors.forename: Jinying
authors.initials: J
authors.lastname: Xu
authors.affiliation: Faculty of Health Sciences, University of Macau, Taipa, Macau, China. Electronic address: wenhuazheng@umac.mo.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Zheng
mesh_terms: D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010446:Peptide Fragments / Q000009:adverse effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D037621:Artemisinins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); C031327:artemisinin; D007770:L-Lactate Dehydrogenase; D020169:Caspases
keywords: Alzheimer's disease; Artemisinin; Aβ25–35; ERK1/2; PC12 cells