The effect of oxidative stress on amyloid precursor protein processing in cells engaged in beta-amyloidosis is related to apolipoprotein E genotype

Acta Neuropathologica
Bozena Mazur-KoleckaJanusz Frackowiak

Abstract

The reduced antioxidative defense in allele epsilon4 carriers is suggested to contribute to beta-amyloidosis in Alzheimer's disease and Down's syndrome. We studied the effect of oxidative stress on accumulation of amyloid-beta peptide (Abeta) in vascular smooth muscle cells (SMCs) that are engaged in production of amyloid-beta in vivo. Previously, we found that oxidative stress caused by ferrous ions induced accumulation of Abeta-apolipoprotein E deposits in lysosomes and was associated with a greater oxidative protein damage in epsilon4 carriers. Here, we demonstrate that ferrous ions induce formation of Abeta deposits also in vascular tunica media in organotypic cultures of whole brain vessels, suggesting the role of oxidative stress in development of vascular beta-amyloidosis. Cellular accumulation of Abeta in SMCs treated with ferrous ions was associated with a greater accumulation of C-terminal amyloid precursor protein (APP) fragments in epsilon4/epsilon4 than in epsilon3/epsilon3 myocytes and reduced the amount of soluble APPalpha in epsilon3/epsilon3, but not epsilon4/epsilon4, cultures. Antioxidant vitamin E prevented these effects, and, when applied alone, diminished the amount of APP C-terminal fragments and increase...Continue Reading

References

Mar 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·G L CaporasoP Greengard
May 11, 1991·Lancet·P R WenhamG Blandell
Nov 1, 1994·Journal of Neuropathology and Experimental Neurology·J FrackowiakH M Wisniewski
Jul 11, 1996·Nature·M A SmithN Kowall
Dec 24, 1995·Brain Research·J WegielZ Soltysiak
Feb 16, 1996·Neuroscience Letters·S HelisalmiH Soininen
Mar 1, 1997·Journal of Neuropathology and Experimental Neurology·B Mazur-KoleckaH M Wisniewski
Sep 2, 1997·Proceedings of the National Academy of Sciences of the United States of America·M A SmithG Perry
Jul 17, 1998·Journal of the Neurological Sciences·M A LovellW R Markesbery
Jan 9, 1999·Trends in Neurosciences·A Alves-RodriguesM E Figueiredo-Pereira
Apr 10, 1999·Journal of Neuropathology and Experimental Neurology·B Mazur-KoleckaH M Wisniewski
Aug 4, 1999·Current Opinion in Lipidology·R W Mahley, Y Huang
Jan 7, 2000·The American Journal of Pathology·G K GourasN R Relkin
Feb 24, 2001·Annals of the New York Academy of Sciences·J Poirier
Mar 16, 2002·Journal of Neuropathology and Experimental Neurology·Dietmar Rudolf ThalHeiko Braak
Mar 20, 2002·Cerebrovascular Diseases·Steven M Greenberg
Apr 4, 2002·Neuroreport·Bozena Mazur-KoleckaDennis Dickson
Jul 31, 2002·Brain Pathology·Tamas ReveszBlas Frangione
Sep 6, 2002·Journal of Alzheimer's Disease : JAD·George PerryMark A. Smith
Sep 6, 2002·Journal of Alzheimer's Disease : JAD·Jorge Ghiso, Blas Frangione
Dec 25, 2002·Neurobiology of Aging·Bozena Mazur-KoleckaAdam Golabek
Jul 2, 2003·Journal of Neuropathology and Experimental Neurology·Janusz FrackowiakBozena Mazur-Kolecka
Feb 28, 2004·Brain Research·Janusz FrackowiakBozena Mazur-Kolecka

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Citations

Jun 20, 2006·Journal of Neuropathology and Experimental Neurology·Ilene D Auerbach, Harry V Vinters
Aug 18, 2005·Neurobiology of Aging·B Mazur-KoleckaJ Frackowiak
Jul 5, 2005·Neurobiology of Aging·Bozena Mazur-KoleckaJanusz Frackowiak
May 28, 2021·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Amanda B ChaiIngrid C Gelissen

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