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Focal adhesion kinase activates NF-κB via the ERK1/2 and p38MAPK Pathways in amyloid-β25-35-induced apoptosis in PC12 cells.
J Alzheimers Dis. 2012; 32(1):77-94.JA

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+Show Affiliations

MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22776966

Citation

Wang, Xichao, et al. "Focal Adhesion Kinase Activates NF-κB Via the ERK1/2 and p38MAPK Pathways in Amyloid-β25-35-induced Apoptosis in PC12 Cells." Journal of Alzheimer's Disease : JAD, vol. 32, no. 1, 2012, pp. 77-94.
Wang X, Chen Q, Xing D. Focal adhesion kinase activates NF-κB via the ERK1/2 and p38MAPK Pathways in amyloid-β25-35-induced apoptosis in PC12 cells. J Alzheimers Dis. 2012;32(1):77-94.
Wang, X., Chen, Q., & Xing, D. (2012). Focal adhesion kinase activates NF-κB via the ERK1/2 and p38MAPK Pathways in amyloid-β25-35-induced apoptosis in PC12 cells. Journal of Alzheimer's Disease : JAD, 32(1), 77-94.
Wang X, Chen Q, Xing D. Focal Adhesion Kinase Activates NF-κB Via the ERK1/2 and p38MAPK Pathways in Amyloid-β25-35-induced Apoptosis in PC12 Cells. J Alzheimers Dis. 2012;32(1):77-94. PubMed PMID: 22776966.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Focal adhesion kinase activates NF-κB via the ERK1/2 and p38MAPK Pathways in amyloid-β25-35-induced apoptosis in PC12 cells. AU - Wang,Xichao, AU - Chen,Qun, AU - Xing,Da, PY - 2012/7/11/entrez PY - 2012/7/11/pubmed PY - 2013/2/21/medline SP - 77 EP - 94 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 32 IS - 1 N2 - 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/22776966/Focal_adhesion_kinase_activates_NF_κB_via_the_ERK1/2_and_p38MAPK_Pathways_in_amyloid_β25_35_induced_apoptosis_in_PC12_cells_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2012-120526 DB - PRIME DP - Unbound Medicine ER -