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Extra resources for Glutathione - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

Sample text

This approach is unique and allows for studies not previously possible. it was observed that the cytokine, interleukin 6, decreases the expression of a number of GST isozymes. The decrease in expression is mediated by elements in the promoter sequence of the GST gene and a unique nuclear protein has been identified that appears to mediate the decrease in transcription. This nuclear protein also is induced in the livers of animals during the acute phase response, and its appearance is associated with a decline in GST expression.

However, the results indicated that the factors governing protection by GST are complex and vary with different agents and endpoints. The studies outlined in this proposal will provide new information on the efficacy and specificity of human GSTP1 or GSTM1 protection against DNA adduct formation or cytotoxicity caused by exposure to PAHs activated in situ by co-expressed rat rCYP1A1 or human hCYP1A1. Heterologous expression of the GST isozymes in V79 cells previously stably transfected with rCYP1A1 or hCYP1A1 will be used as the experimental model system.

Further, we will delineate the roles of GCLC and GCLM in controlling GSH levels. These studies will provide valuable insight into understanding the etiology, preventive medicine, and the possible development of therapeutic intervention in the above-mentioned diseases and toxicities. For example, studies suggest that human genetic differences exist in toxicity to cadmium and other environmental toxicants that cause oxidative stress; moreover, the GCLC and GCLM genes are highly polymorphic. Our proposed research should therefore help focus future genotype-phenotype association studies between the appropriate DNA variant sites in the GCLC and GCLM genes and disease.

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