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 language | English (US) |
|---|---|
| Pages (from-to) | 10169-10174 |
| Number of pages | 6 |
| Journal | Journal of Biological Chemistry |
| Volume | 271 |
| Issue number | 17 |
| DOIs | |
| State | Published - Apr 26 1996 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - 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
AU - Frederikse, Peter H.
AU - Garland, Donita
AU - Zigler, J. Samuel
AU - Piatigorsky, Joram
PY - 1996/4/26
Y1 - 1996/4/26
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0029985732&partnerID=8YFLogxK
U2 - 10.1074/jbc.271.17.10169
DO - 10.1074/jbc.271.17.10169
M3 - Article
C2 - 8626578
AN - SCOPUS:0029985732
VL - 271
SP - 10169
EP - 10174
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 17
ER -