title: Focal adhesion kinase activates NF-κB via the ERK1/2 and p38MAPK Pathways in amyloid-β25-35-induced apoptosis in PC12 cells.
abstract: Increasing evidence supports that amyloid plaques, comprised of amyloid-β (Aβ), are a key feature of Alzheimer's disease (AD). But the mechanism of Aβ in AD is not yet fully understood. Previous studies have demonstrated that in Aβ-induced apoptosis of nerve cells, differentiated rat pheochromocytoma (PC12) cells, and microglia, nucleus factor kappa B (NF-κB) is activated. Meanwhile, focal adhesion kinase (FAK) is also activated. However, the relationship between NF-κB and FAK remains unclear. Using differentiated PC12 cells, we investigated this relationship in Aβ(25-35)-induced apoptosis. The results showed that FAK phosphorylation increased at 6-9 hours after Aβ treatment, slightly shorter than the activation of NF-κB (6-12 hours). In this process, both extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation levels were increased. After FAK expression was inhibited by its siRNA, the activities of ERK1/2, p38MAPK, and NF-κB were all suppressed. When ERK1/2 and p38MAPK expressions were inhibited by their siRNAs respectively, NF-κB activity was also suppressed. But FAK phosphorylation was not affected. When NF-κB expression was inhibited, all of the phosphorylation levels of FAK, ERK1/2, and p38MAPK were not affected. These phenomena indicated that FAK is upstream of ERK1/2, p38MAPK, and NF-κB, and meanwhile both of ERK1/2 and p38MAPK are upstream of NF-κB. Co-immunoprecipitation results demonstrated that it is ERK1/2, but not p38MAPK, which directly interacts with IκB kinase. Taken together, our results suggest that FAK activates NF-κB via ERK1/2 and p38MAPK pathways in Aβ(25-35)-induced apoptosis of differentiated PC12 cells.
authors: MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.
authors: Xichao
authors: X
authors: Wang
authors: Qun
authors: Q
authors: Chen
authors: Da
authors: D
authors: Xing
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000502:physiology; D005434:Flow Cytometry; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology*; D051550:I-kappa B Kinase / Q000502:physiology; D047468:Immunoprecipitation; D007202:Indicators and Reagents; D020935:MAP Kinase Signaling System / Q000502:physiology*; D016328:NF-kappa B / Q000737:chemistry / Q000502:physiology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation; D034622:RNA Interference; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D007202:Indicators and Reagents; D016328:NF-kappa B; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D051416:Focal Adhesion Protein-Tyrosine Kinases; D051550:I-kappa B Kinase; D048051:p38 Mitogen-Activated Protein Kinases