The Dose-Dependent Effect of Ethanol on sAPPα Secretion from CHO695 Cells
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Authors
Goyal, Renu
Issue Date
2004
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Alcohol is an immunosuppressive drug that has been found to have an inhibitory
effect on immune responses. Previous researchers have shown the inhibitory effect of
EtOH on TNF-alpha secretion. With the intense study ofEtOH's effect on the secretion
of TNF-alpha, the interest of the effect of EtOH on the brain has been instigated. APP,
the amyloid precursor protein, is a significant nervous system and transmembrane protein found in the brain and is under study due to the formation of Afβ plaques in the brain during the onset of Alzheimer's disease. Through the study of Alzheimer's patients, a further understanding of APP in the brain has been assessed.
TACE, TNF-alpha converting enzyme, is important in both proteins of interest,
APP and TNF. TACE is an α-secretase that is effected by the addition of various
concentrations o fEtOH and is involved in a posttranscriptional process called
ectodornain shedding. Levels of APP substrate in the brain are affected by the levels of
EtOH.
This study consisted of determining the effects of ethanol on the secretion of
sAPP-alpha with1he presence and absence of PMA, Phorbol 12-Myristate 13-Acetate, a
TACE stimulator. Chinese Hamster Ovary cells, CH0695, cells were grown in
Dulbecco's Modified Eagle Medium, DMEM and incubated in ethanol concentrations
varying from 0, 5, 10, 15, 25, to lethal doses of EtOH at 75mM. The results of the
conducted study showed a dose-dependent decrease in sAPP-alpha secretion. These
results support the prediction that the levels of sAPP-alpha would decrease as EtOH
concentrations increased. There was no general change in cellular APP levels with
increasing EtOH. However, at lethal doses of EtOH, 75 mM, the cellular APP was
completely degraded, therefore making sAPP-alpha secretion unattainable. By further
studying the effect of alcohol on the secretion of sAPP-alpha, we plan on defining its role
in brain function. The results of the experiment illustrated that at high levels of EtOH
concentrations, the substrate, APP, is completely degraded. Without the presence of
APP, sAPP-alpha cannot be secreted.
Description
v, 24 p.
Citation
Publisher
Kalamazoo College
License
U.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.