Caspase-8 Mediates Amyloid-β-induced Apoptosis in Differentiated PC12 Cells

• Published in: Journal of molecular neuroscience 2015-06, Vol.56 (2), p.491-499
• Main Authors: Qian, Min-cai, Liu, Jing, Yao, Jia-shu, Wang, Wei-min, Yang, Jian-hong, Wei, Li-li, Shen, Yue-di, Chen, Wei
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - toxicity; Animals; Apoptosis; Biomedical and Life Sciences; Biomedicine; Caspase 3 - metabolism; Caspase 8 - genetics; Caspase 8 - metabolism; Caspase 9 - metabolism; Cell Biology; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Neurochemistry; Neurology; Neurons - drug effects; Neurons - metabolism; Neurosciences; PC12 Cells; Peptide Fragments - toxicity; Proteomics; Proto-Oncogene Proteins c-akt - metabolism; Rats
• ISSN: 0895-8696; 1559-1166
• DOI: 10.1007/s12031-015-0498-5

The pathogenesis of Alzheimer’s disease (AD) is very complex and there are currently no significant treatments for the disease. Caspase-8 is known to be involved in neuronal apoptosis. To explore a possible molecular mechanisms involved in AD pathology, this study investigated the effect of caspase-8 knockdown on amyloid-β 1–40 (Aβ1–40)-induced apoptosis in PC12 cells. The proliferation of PC12 cells was significantly inhibited in Aβ-treated cells, and a high fraction of the cells underwent apoptosis in a dose- and time-dependent manner. Transfection of caspase-8 small interfering RNA (siRNA) resulted in reduced apoptosis following Aβ1–40 treatment. The activation of caspase-3, caspase-8, and caspase-9 was stimulated by Aβ1–40, an effect that was also significantly reduced by caspase-8 siRNA. Knockdown of caspase-8 increased the phosphorylation of the signaling molecules AKT and ERK1/2 relative to cells treated with Aβ1–40 alone. Caspase-8 is an important effector molecule involved in apoptosis induced by Aβ1–40 and is likely involved in AD pathology. This study suggests that targeted inhibition of caspase-8 may be a new therapeutic for preventing neuronal apoptosis and inhibiting the progression of AD.