Oxidative stress increases production of β-amyloid precursor protein and β-amyloid (Aβ) in mammalian lenses, and Aβ has toxic effects on lens epithelial cells

Peter H. Frederikse, Donita Garland, J. Samuel Zigler, Joram Piatigorsky

Research output: Contribution to journalArticle

Abstract

Many amyloid diseases are characterized by protein aggregations linked to oxidative stress. Such diseases including those of the brain, muscle, and blood vessels exhibit plaques containing β-amyloid (Aβ). Here we demonstrate that Alzheimer's precursor protein (βAPP) and Aβ are present at low levels in normal lenses and increase in intact cultured monkey lenses treated with H2O2 or UV radiation (known cataractogenic agents), and with phorbol 12-myristate 13-acetate. AP-1 factor binding, shown by others to up- regulate βAPP expression, increased in the monkey lenses treated with H2O2, UV radiation, or phorbol 12-myristate 13-acetate and paralleled the increase in βAPP expression. Rat lenses exposed to oxidative stress showed increased βAPP in the anterior epithelium and cortex. Incubation of cultured rabbit lens N/N1003A epithelial cells with Aβ induced inclusions and vacuoles and was cytotoxic. Aβ cross-reacting protein was readily detected in the cortex of a cataractous human lens. Our data show that βAPP and Aβ increase in mammalian lenses as part of a response to H2O2 or UV radiation and suggest that they may contribute to the mechanism by which oxidative damage leads to lens opacification.

Original languageEnglish (US)
Pages (from-to)10169-10174
Number of pages6
JournalJournal of Biological Chemistry
Volume271
Issue number17
DOIs
StatePublished - Apr 26 1996
Externally publishedYes

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Oxidative stress
Amyloid beta-Protein Precursor
Poisons
Amyloid
Lenses
Oxidative Stress
Epithelial Cells
Protein Precursors
Ultraviolet radiation
Staphylococcal Protein A
Radiation
Haplorhini
Acetates
Transcription Factor AP-1
Amyloid Plaques
Blood vessels
Vacuoles
Blood Vessels
Muscle
Rats

ASJC Scopus subject areas

  • Biochemistry

Cite this

Oxidative stress increases production of β-amyloid precursor protein and β-amyloid (Aβ) in mammalian lenses, and Aβ has toxic effects on lens epithelial cells. / Frederikse, Peter H.; Garland, Donita; Zigler, J. Samuel; Piatigorsky, Joram.

In: Journal of Biological Chemistry, Vol. 271, No. 17, 26.04.1996, p. 10169-10174.

Research output: Contribution to journalArticle

Frederikse, Peter H. ; Garland, Donita ; Zigler, J. Samuel ; Piatigorsky, Joram. / Oxidative stress increases production of β-amyloid precursor protein and β-amyloid (Aβ) in mammalian lenses, and Aβ has toxic effects on lens epithelial cells. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 17. pp. 10169-10174.
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