Effects of Inhibiting Iron-Dependent Lipid Peroxidation on Aging
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Authors
Van Cise, Michelle Lynn
Issue Date
1987
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Aging is an unavoideble process end the mechanisms involved in the
cell's demise are still unknown. This study attempted to alter the level
of iron-dependent lipid peroxidation in the tissue culture environment
by adding known entioxidants to the in vitro cellular environment.
Compounds used to accomplish th1s were desferroxamine, vitamin E,
U74500A end U74006F. It is proposed that these compounds may act by
chelating iron which is required for catalyzation of the ininitiation of
lipid peroxidation, except for vitamin E end 74006F which are
anti-oxidants whose protective mechanisms involve the scavenging of
detrimental species such as the superoxide anion, the hydroxl radical
and hydrogen peroxide.
Experimentation occurred on three human diploid fibroblastic cell
lines: MRC-5, WI 1003, and primary prostatic stroma. Two of these
cell types, MRC-5 and WI 1003, were selected because of their
derivation from lung tissue, resembling the WI-38 cells used in
previous cytogerontological studies. These cells were
subjected to concentretions of each drug which were determined to be
optimal for the maintenance of cell morphology and fiability. Parallel
cultures of each cell type were treated with one of the four drug
solutions over their lifespan. The results indicate that MRC-5 and WI
1003 cells treated with desferroxamine increase cell number with
each subcultivation. The prostatic stromal cells exhibited a higher cell
count with the 74006 drug treatment. In all cases, cells treated w1th
drug had higher cell counts than drug-free controls. Experiments
designed to reveal differences in DNA synthesis rates and DNA content
through triated thymidine pulses and flow cytomentry respectively,
showed no correlation with drug treatment. Experiments using
epithelial cells to assay for levels of secretion of a marker protein,
PSP-15, revealed that cells treated with U74500A in particular,
secreted more of the protein than control cells when grown on an
extracellular matrix.
The results of this study suggest that the addition of an iron
chelator to media used in mammalian cell culture may improve cell
viability and expression of cellular differentiated function. The tissue
culture setting represents an ischemic environment where generation
of lipid peroxidation catalyzed by iron can occur. The protective
effects of the drugs tested here would warrant similar experiments at
the organ culture level to find optimal protective concentrations to use
in organ perfusion prior to reimplantation.
Description
35 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.