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Death of PC12 cells and hippocampal neurons induced by adenoviral-mediated FAD human amyloid precursor protein gene expression

1999; Wiley; Volume: 55; Issue: 5 Linguagem: Inglês

10.1002/(sici)1097-4547(19990301)55

1097-4547

Jin Jun Luo, William Wallace, Teresa Riccioni, Donald K. Ingram, George S. Roth, John W. Kusiak,

Prion Diseases and Protein Misfolding

Journal of Neuroscience ResearchVolume 55, Issue 5 p. 629-642 Article Death of PC12 cells and hippocampal neurons induced by adenoviral-mediated FAD human amyloid precursor protein gene expression Jin-Jun Luo, Corresponding Author Jin-Jun Luo [email protected] Molecular Neurobiology Unit, Laboratory of Biological Chemistry, National Institute on Aging, Baltimore, MarylandMail Stop 12, MNU, LBC, GRC, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224.Search for more papers by this authorWilliam Wallace, William Wallace Molecular Neurobiology Unit, Laboratory of Biological Chemistry, National Institute on Aging, Baltimore, MarylandSearch for more papers by this authorTeresa Riccioni, Teresa Riccioni Laboratory of Cardiovascular Sciences, National Institute on Aging, Baltimore, MarylandSearch for more papers by this authorDonald K. Ingram, Donald K. Ingram Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, MarylandSearch for more papers by this authorGeorge S. Roth, George S. Roth Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, MarylandSearch for more papers by this authorJohn W. Kusiak, John W. Kusiak Molecular Neurobiology Unit, Laboratory of Biological Chemistry, National Institute on Aging, Baltimore, MarylandSearch for more papers by this author Jin-Jun Luo, Corresponding Author Jin-Jun Luo [email protected] Molecular Neurobiology Unit, Laboratory of Biological Chemistry, National Institute on Aging, Baltimore, MarylandMail Stop 12, MNU, LBC, GRC, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224.Search for more papers by this authorWilliam Wallace, William Wallace Molecular Neurobiology Unit, Laboratory of Biological Chemistry, National Institute on Aging, Baltimore, MarylandSearch for more papers by this authorTeresa Riccioni, Teresa Riccioni Laboratory of Cardiovascular Sciences, National Institute on Aging, Baltimore, MarylandSearch for more papers by this authorDonald K. Ingram, Donald K. Ingram Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, MarylandSearch for more papers by this authorGeorge S. Roth, George S. Roth Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, MarylandSearch for more papers by this authorJohn W. Kusiak, John W. Kusiak Molecular Neurobiology Unit, Laboratory of Biological Chemistry, National Institute on Aging, Baltimore, MarylandSearch for more papers by this author First published: 23 February 1999 https://doi.org/10.1002/(SICI)1097-4547(19990301)55:5 3.0.CO;2-YCitations: 34AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract We used adenoviral-mediated gene transfer of human amyloid precursor proteins (h-APPs) to evaluate the role of various h-APPs in causing neuronal cell death. We were able to infect PC12 cells with very high efficiency because ≈90% of the cells were cytochemically positive for β-galactosidase activity when an adenoviral vector containing LacZ cDNA was used to infect cells. Cells infected with adenovirus containing h-APP cDNA showed high-level transcription and expression of h-APP as measured by reverse transcriptase–polymerase chain reaction and Western immunoblot analyses, respectively. Intracellular and extracellular levels of h-APP were elevated approximately 17- and 24-fold in cultures infected with recombinant adenovirus containing wild-type mutant and 13- and 17-fold with V642F mutant. No elevation in h-APP was seen in cultures infected with antisense h-APP or null adenovirus. H-APP levels were maximal 3 days after infection. Overexpression of V642F mutant h-APP in PC12 cells and hippocampal neurons resulted in about a twofold increase in death compared with overexpression of wild-type h-APP. 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