The Role of C-Fos and C-Jun Expression in the Induction of Glutathione S-Transferase 7-7 by Lead Nitrate
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Authors
Coller, Dale Arold
Issue Date
1993
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Lead toxicity is a major health issue in the United States. It has been linked to metabolic, neurological, growth, and behavioral disorders.
To date the biochemical mechanisms of lead toxicity are not well
understood. It has been proposed that many effects of lead result from
perturbation of signal-transduction processes mediated by a calcium
messenger system (Pounds, 1984; Pounds et al., 1991). A potential
consequence of altered calcium homeostasis in many tissues is altered
expression of intermediate early genes. The placental glutathione Stransferase
(GST 7-7) proteins can be induced, both in synthesis and
activity, by lead exposure, and are regulated, at least in part, by
intermediate early genes. The GST 7-7 gene contains an activation one
protein (AP-1) binding site which is activated by dimerized c-fos and c-jun
proteins. In this study the effect of lead nitrate on the induction of
GST 7-7 through the stimulation of the AP-1 components c-fos and c-jun
was examined. Male Sprague-Dawley rats were injected intravenously in
with 10 µmol of lead nitrate per kilogram of body weight and were
sacrificed at selected time intervals after injection (1, 2, 6, 12, 24, 48,
and 72 hours post injection). Cytosolic proteins, nuclear proteins, total
RNA and poly (A)+ m RNA were extracted from the liver tissue of these
animals and examined using the techniques of SDS-PAGE electrophoresis,
western immunoblot analysis, agarose electrophoresis, and P32 labeling
of cDNA probes for Northern blot analysis. Through 1,2-dichloro-4-
nitrobenzene substrate (CDNB) activity assays and immunoblot analysis of
liver cytosol, lead nitrate was found to induce the synthesis of GST' 7-7.
Northern Blot analysis of liver poly (A)+ RNA for the first time showed cjun
expression to increase 4 fold over the first 6 hours of exposure and cfos
expression to increase 10 fold over 48 hours of lead nitrate exposure.
The time difference in the increased expression of the proto-oncogenes
fos and jun implies that the heterodimer form of the AP-1 transfactor
protein is not responsible of the induction of GST 7-7 by exposure to lead.
Description
vi, 42 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.