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Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media

In comparing two human lung cancer cells, we previously found lower levels of acetylcholinesterase (AChE) and intact amyloid-β40/42 (Aβ), and higher levels of mature brain-derived neurotrophic factor (mBDNF) in the media of H1299 cells as compared to A549 cell media. In this study, we hypothesized t...

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Autores principales: Al Khashali, Hind, Ray, Ravel, Coleman, Kai-Ling, Atali, Sarah, Haddad, Ben, Wareham, Jadziah, Guthrie, Jeffrey, Heyl, Deborah, Evans, Hedeel Guy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500850/
https://www.ncbi.nlm.nih.gov/pubmed/36142659
http://dx.doi.org/10.3390/ijms231810746
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author Al Khashali, Hind
Ray, Ravel
Coleman, Kai-Ling
Atali, Sarah
Haddad, Ben
Wareham, Jadziah
Guthrie, Jeffrey
Heyl, Deborah
Evans, Hedeel Guy
author_facet Al Khashali, Hind
Ray, Ravel
Coleman, Kai-Ling
Atali, Sarah
Haddad, Ben
Wareham, Jadziah
Guthrie, Jeffrey
Heyl, Deborah
Evans, Hedeel Guy
author_sort Al Khashali, Hind
collection PubMed
description In comparing two human lung cancer cells, we previously found lower levels of acetylcholinesterase (AChE) and intact amyloid-β40/42 (Aβ), and higher levels of mature brain-derived neurotrophic factor (mBDNF) in the media of H1299 cells as compared to A549 cell media. In this study, we hypothesized that the levels of soluble amyloid precursor protein α (sAPPα) are regulated by AChE and mBDNF in A549 and H1299 cell media. The levels of sAPPα were higher in the media of H1299 cells. Knockdown of AChE led to increased sAPPα and mBDNF levels and correlated with decreased levels of intact Aβ40/42 in A549 cell media. AChE and mBDNF had opposite effects on the levels of Aβ and sAPPα and were found to operate through a mechanism involving α-secretase activity. Treatment with AChE decreased sAPPα levels and simultaneously increased the levels of intact Aβ40/42 suggesting a role of the protein in shifting APP processing away from the non-amyloidogenic pathway and toward the amyloidogenic pathway, whereas treatment with mBDNF led to opposite effects on those levels. We also show that the levels of sAPPα are regulated by protein kinase C (PKC), extracellular signal-regulated kinase (ERK)1/2, phosphoinositide 3 Kinase (PI3K), but not by protein kinase A (PKA).
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spelling pubmed-95008502022-09-24 Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media Al Khashali, Hind Ray, Ravel Coleman, Kai-Ling Atali, Sarah Haddad, Ben Wareham, Jadziah Guthrie, Jeffrey Heyl, Deborah Evans, Hedeel Guy Int J Mol Sci Article In comparing two human lung cancer cells, we previously found lower levels of acetylcholinesterase (AChE) and intact amyloid-β40/42 (Aβ), and higher levels of mature brain-derived neurotrophic factor (mBDNF) in the media of H1299 cells as compared to A549 cell media. In this study, we hypothesized that the levels of soluble amyloid precursor protein α (sAPPα) are regulated by AChE and mBDNF in A549 and H1299 cell media. The levels of sAPPα were higher in the media of H1299 cells. Knockdown of AChE led to increased sAPPα and mBDNF levels and correlated with decreased levels of intact Aβ40/42 in A549 cell media. AChE and mBDNF had opposite effects on the levels of Aβ and sAPPα and were found to operate through a mechanism involving α-secretase activity. Treatment with AChE decreased sAPPα levels and simultaneously increased the levels of intact Aβ40/42 suggesting a role of the protein in shifting APP processing away from the non-amyloidogenic pathway and toward the amyloidogenic pathway, whereas treatment with mBDNF led to opposite effects on those levels. We also show that the levels of sAPPα are regulated by protein kinase C (PKC), extracellular signal-regulated kinase (ERK)1/2, phosphoinositide 3 Kinase (PI3K), but not by protein kinase A (PKA). MDPI 2022-09-15 /pmc/articles/PMC9500850/ /pubmed/36142659 http://dx.doi.org/10.3390/ijms231810746 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Al Khashali, Hind
Ray, Ravel
Coleman, Kai-Ling
Atali, Sarah
Haddad, Ben
Wareham, Jadziah
Guthrie, Jeffrey
Heyl, Deborah
Evans, Hedeel Guy
Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media
title Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media
title_full Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media
title_fullStr Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media
title_full_unstemmed Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media
title_short Regulation of the Soluble Amyloid Precursor Protein α (sAPPα) Levels by Acetylcholinesterase and Brain-Derived Neurotrophic Factor in Lung Cancer Cell Media
title_sort regulation of the soluble amyloid precursor protein α (sappα) levels by acetylcholinesterase and brain-derived neurotrophic factor in lung cancer cell media
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9500850/
https://www.ncbi.nlm.nih.gov/pubmed/36142659
http://dx.doi.org/10.3390/ijms231810746
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