Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media
Abstract
:1. Introduction
2. Results
2.1. Cell Treatment with the AChE Inhibitor, Neostigmine, Led to Increased sAPPα Levels in A549 Cell Media That Were Comparable to Those Detected in the Media of H1299 cells
2.2. Knockdown of AChE Led to Increased ACh and mBDNF Levels in A549 Cell Media
2.3. Lower Levels of Aβ40 and Aβ42 Were Observed in A549 Cell Media upon Transfection with AChE siRNA and Correlated with Higher sAPPα Levels
2.4. AChE and mBDNF Have Opposite Effects on the Levels of Aβ and sAPPα and Operate through a Mechanism Involving α-Secretase Activity
2.5. Minimal Effects Were Observed on the Levels of sAPPα in A549 and H1299 Cell Media upon Blocking Protein Kinase A (PKA) Activity
2.6. The Levels of sAPPα Decreased in the Media of A549 and H1299 Cells upon Treatment with the PKC Inhibitor, Chelerythrine
2.7. A more Pronounced Decrease in the Levels of sAPPα Was Observed in A549 and H1299 Cell Media When the Activities of ERK1/2 and PKC Were Blocked Using a Combination of PD98059 and Chelerythrine
2.8. The Levels of sAPPα Were Decreased to a Greater Extent in the Media upon Co-Treatment of A549 and H1299 Cells with ACh or mBDNF, the PI3K Inhibitor, LY294002, and Either the ERK1/2 Inhibitor or PKC Inhibitor Compared to Cell Co-Treatment with LY294002 Alone
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Cell Culture
4.3. ELISA
4.4. Quantitation of ACh Concentrations
4.5. Quantitative Determination of sAPPα
4.6. Quantitation of Aβ
4.7. PKC Assay
4.8. PKA Assay
4.9. ERK Assay
4.10. PI3K Assay
4.11. Quantitation of mBDNF
4.12. Western Blotting
4.13. SiRNA Transfection
4.14. Statistical Analysis
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Al Khashali, H.; Ray, R.; Coleman, K.-L.; Atali, S.; Haddad, B.; Wareham, J.; Guthrie, J.; Heyl, D.; Evans, H.G. Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media. Int. J. Mol. Sci. 2022, 23, 10746. https://doi.org/10.3390/ijms231810746
Al Khashali H, Ray R, Coleman K-L, Atali S, Haddad B, Wareham J, Guthrie J, Heyl D, Evans HG. Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media. International Journal of Molecular Sciences. 2022; 23(18):10746. https://doi.org/10.3390/ijms231810746
Chicago/Turabian StyleAl Khashali, Hind, Ravel Ray, Kai-Ling Coleman, Sarah Atali, Ben Haddad, Jadziah Wareham, Jeffrey Guthrie, Deborah Heyl, and Hedeel Guy Evans. 2022. "Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media" International Journal of Molecular Sciences 23, no. 18: 10746. https://doi.org/10.3390/ijms231810746