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Artemisinin protects PC12 cells against β -amyloid-induced apoptosis through activation of the ERK1/2 signaling pathway

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Artemisinin suppressed Aβ1-42-induced cell viability lose in PC12 cells. (A) Cells were treated with Aβ1-42 (0.001–1 μM) or 0.1% DMSO (vehicle control) for 24 h and cell viability was measured using the MTT assay. (B) Cells were pre-treated with artemisinin(25 μM) or 0.1% DMSO (vehicle control) for 1 h and then incubated with or without 0.3 μM Aβ1-42 for a further 24 h and cell viability were measured by MTT assay (N=3). ###P<0.005 versus control group; **P<0.01 versus the Aβ1-42 treated group was considered statistically differences.
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f0035: Artemisinin suppressed Aβ1-42-induced cell viability lose in PC12 cells. (A) Cells were treated with Aβ1-42 (0.001–1 μM) or 0.1% DMSO (vehicle control) for 24 h and cell viability was measured using the MTT assay. (B) Cells were pre-treated with artemisinin(25 μM) or 0.1% DMSO (vehicle control) for 1 h and then incubated with or without 0.3 μM Aβ1-42 for a further 24 h and cell viability were measured by MTT assay (N=3). ###P<0.005 versus control group; **P<0.01 versus the Aβ1-42 treated group was considered statistically differences.

Mentions: Because Aβ25–35 is a shorter toxic fragment (active component of Aβ1–42), people will desire to see the effect of Aβ1-42 itself on the PC12 cells and the protection of artemisinin on the toxic effect of Aβ1-42. Similarly, as shown in Fig. 7A, cells exposed to Aβ1-42 for 24 h resulted in a remarkable cell viability reduction, and as shown in Fig. 7B, artemisinin significantly protected PC12 cells from toxicity of Aβ1-42.


Artemisinin protects PC12 cells against β -amyloid-induced apoptosis through activation of the ERK1/2 signaling pathway
Artemisinin suppressed Aβ1-42-induced cell viability lose in PC12 cells. (A) Cells were treated with Aβ1-42 (0.001–1 μM) or 0.1% DMSO (vehicle control) for 24 h and cell viability was measured using the MTT assay. (B) Cells were pre-treated with artemisinin(25 μM) or 0.1% DMSO (vehicle control) for 1 h and then incubated with or without 0.3 μM Aβ1-42 for a further 24 h and cell viability were measured by MTT assay (N=3). ###P<0.005 versus control group; **P<0.01 versus the Aβ1-42 treated group was considered statistically differences.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5385605&req=5

f0035: Artemisinin suppressed Aβ1-42-induced cell viability lose in PC12 cells. (A) Cells were treated with Aβ1-42 (0.001–1 μM) or 0.1% DMSO (vehicle control) for 24 h and cell viability was measured using the MTT assay. (B) Cells were pre-treated with artemisinin(25 μM) or 0.1% DMSO (vehicle control) for 1 h and then incubated with or without 0.3 μM Aβ1-42 for a further 24 h and cell viability were measured by MTT assay (N=3). ###P<0.005 versus control group; **P<0.01 versus the Aβ1-42 treated group was considered statistically differences.
Mentions: Because Aβ25–35 is a shorter toxic fragment (active component of Aβ1–42), people will desire to see the effect of Aβ1-42 itself on the PC12 cells and the protection of artemisinin on the toxic effect of Aβ1-42. Similarly, as shown in Fig. 7A, cells exposed to Aβ1-42 for 24 h resulted in a remarkable cell viability reduction, and as shown in Fig. 7B, artemisinin significantly protected PC12 cells from toxicity of Aβ1-42.

View Article: PubMed Central - PubMed

ABSTRACT

Accumulating evidence displays that an abnormal deposition of amyloid beta-peptide (A&beta;) is the primary cause of the pathogenesis of Alzheimer's disease (AD). And therefore the elimination of A&beta; is regarded as an important strategy for AD treatment. The discovery of drug candidates using culture neuronal cells against A&beta; 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 &beta; amyloid peptide. Our studies revealed that artemisinin, in clinical relevant concentration, protected and rescued PC12 cells from A&beta;25&ndash;35-induced cell death. Further study showed that artemisinin significantly ameliorated cell death due to A&beta;25&ndash;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, A&beta;1-42 also caused cells death of PC12 cells while artemisinin suppressed A&beta;1-42 cytotoxicity in PC12 cells. Taken together, these results, at the first time, suggest that artemisinin is a potential protectant against &beta; amyloid insult through activation of the ERK1/2 pathway. Our finding provides a potential application of artemisinin in prevention and treatment of AD.

No MeSH data available.