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Your Environment. Your Health.

Progress Reports: University of Washington: Effects Related Biomarkers of Toxic Exposures

Superfund Research Program

Effects Related Biomarkers of Toxic Exposures

Project Leader: Terrance J. Kavanagh
Grant Number: P42ES004696
Funding Period: 1995 - 2006

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Progress Reports

Year:   2005  2004  2003  2002  2001  2000  1999  1998  1997  1996  1995 

As part of efforts to characterize regulatory regions of mGLCLC and mGLCLR, project investigators have subcloned the 5' regions of mouse GLCLR and GLCLC into reporter vectors (including luciferase and green fluorescent protein reporters) to assess in mammalian cell culture experiments, and to clarify their role in regulating basal and inducible mRNA expression. Evidence to date indicates that the mouse GLCLC 5' promoter is a strong constitutive promoter in Hepa-1 mouse liver cells, but that regions 5' of the ARE cooperate in inducibility.

Further work is focusing on post-translational modifications of GLCL resulting from oxidative treatments, such as methyl mercury (MeHg). Using Northern analysis, in situ hybridization, Western analysis, immunocytochemistry and HPLC assays, investigators are examining the effects of MeHg exposure on GLCL expression and activity and GSH levels in various tissues in mice, to localize expression changes at the individual tissue/cell level. Preliminary findings suggest that GLCL may be down-regulated in certain tissues (lung, intestine) with MeHg exposure as opposed to being up-regulated in kidney, liver and brain. Other directions that are being pursued include investigation of the role of the GAG repeat polymorphism in the 5' region of the human GLCL gene in idiopathic pulmonary fibrosis, a disease considered likely to have a strong oxidative stress pathogenic component.

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