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.

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