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Chronic hypoxia in the human neuroblastoma SH-SY5Y causes reduced expression of the putative alpha-secretases, ADAM10 and TACE, without altering their mRNA levels

Marshall, A.J., Rattray, M. and Vaughan, P.F. (2006) Chronic hypoxia in the human neuroblastoma SH-SY5Y causes reduced expression of the putative alpha-secretases, ADAM10 and TACE, without altering their mRNA levels. Brain Research, 1099 (1). pp. 18-24. ISSN 0006-8993

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To link to this article DOI: 10.1016/j.brainres.2006.05.008

Abstract/Summary

Alzheimer's disease is more frequent following an ischemic or hypoxic episode, with levels of beta-amyloid peptides elevated in brains from patients. Similar increases are found after experimental ischemia in animals. It is possible that increased beta-amyloid deposition arises from alterations in amyloid precursor protein (APP) metabolism, indeed, we have shown that exposing cells of neuronal origin to chronic hypoxia decreased the secretion of soluble APP (sAPPalpha) derived by action of alpha-secretase on APP, coinciding with a decrease in protein levels of ADAM10, a disintegrin metalloprotease which is thought to be the major alpha-secretase. In the current study, we extended those observations to determine whether the expression of ADAM10 and another putative alpha-secretase, TACE, as well as the beta-secretase, BACE1 were regulated by chronic hypoxia at the level of protein and mRNA. Using Western blotting and RT-PCR, we demonstrate that after 48 h chronic hypoxia, such that sAPPalpha secretion is decreased by over 50%, protein levels of ADAM10 and TACE and by approximately 60% and 40% respectively with no significant decrease in BACE1 levels. In contrast, no change in the expression of the mRNA for these proteins could be detected. Thus, we conclude that under CH the level of the putative alpha-secretases, ADAM10 and TACE are regulated by post-translational mechanisms, most probably proteolysis, rather than at the level of transcription.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:15725
Uncontrolled Keywords:ADAM Proteins/genetics/*metabolism Amyloid Precursor Protein Secretases Aspartic Acid Endopeptidases Blotting, Western/methods Cell Hypoxia/*physiology Cell Line, Tumor Endopeptidases/genetics/*metabolism Gene Expression Regulation/*physiology Humans Membrane Proteins/*metabolism Neuroblastoma RNA, Messenger/metabolism Reverse Transcriptase Polymerase Chain Reaction/methods
Additional Information:Marshall, Amy J Rattray, Marcus Vaughan, Peter F T Comparative Study Netherlands Brain research Brain Res. 2006 Jul 12;1099(1):18-24. Epub 2006 Jun 9.
Publisher:Elsevier

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