Date of Award
12-2000
Degree Name
Master of Science
Department
Biological Sciences
First Advisor
Dr. Susan R. Stapleton
Second Advisor
Dr. David S. Reinhold
Third Advisor
Dr. John M. Spitsbergen
Access Setting
Masters Thesis-Open Access
Abstract
Cells respond to cadmium (Cd), a common environmental contaminate, by potentially decreasing reduced intracellular glutathione, as well as, increasing the expression of several antioxidant genes. One of these antioxidant genes, glucose-6- phosphate dehydrogenase (G6PDH), is the rate limiting enzyme of the pentose phosphate pathway. This pathway produces NADPH which is used for maintenance of reduced glutathione so, it is hypothesized that Cd should increase G6PDH expression. In this study, we demonstrate that Cd increases the level of G6PDH mRNA in primary rat hepatocytes in culture. In the presence of the antioxidants, N-acetylcysteine (NAC), Trolox, or glutathione monoethyl ester an attenuation of this effect was observed. It has been demonstrated in several instances that Cd can activate genes through signal transduction pathways mediated by stress-response proteins such as mitogen activated protein kinase (MAPK) or c-jun N-terminal kinase (JNK). We also show that Cd activates both MAPK and JNK. In the presence of antioxidants NAC or Trolox, a decrease in activation of MAPK and JNK is observed. Using the well defined MAPK inhibitor, PD098059, we also show that proteins preceding MAPK in this pathway may influence the expression of the G6PDH gene.
Recommended Citation
Maki, Daisuke, "Cadmium Induced Gene Expression and Signal Transduction Pathway" (2000). Masters Theses. 4571.
https://scholarworks.wmich.edu/masters_theses/4571