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Lead suppresses chimeric human transferrin gene expression in transgenic mouse liver
G S Adrian1, E V Rivera, E K Adrian
1Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762.
Neurotoxicology
|January 1, 1993
Summary
Lead exposure suppresses human transferrin (TF) synthesis at the mRNA level in transgenic mice and human cells. This regulation mechanism differs from mouse TF, which remains unaffected by lead.
Area of Science:
- Biochemistry
- Toxicology
- Genetics
Background:
- Transferrin (TF) is the primary serum iron-transport protein with broader metal-binding capabilities.
- Understanding the regulation of TF synthesis is crucial for metal homeostasis and toxicity studies.
Purpose of the Study:
- To investigate the effect of lead exposure on human transferrin (TF) gene expression.
- To determine if lead regulates TF synthesis at the transcriptional or post-transcriptional level.
Main Methods:
- Utilized transgenic mice carrying human TF-chloramphenicol acetyl transferase (CAT) reporter genes.
- Administered lead or sodium salts via intraperitoneal injection and drinking water.
- Assessed transgene expression, CAT enzyme activity, protein levels, and mRNA using molecular biology techniques.
Main Results:
- Lead treatment suppressed human TF-CAT transgene expression in mouse liver by 31-50% at the mRNA level.
- Lead exposure did not affect endogenous mouse TF or albumin synthesis.
- Lead also suppressed TF protein synthesis in cultured human hepatoma HepG2 cells.
Conclusions:
- Lead exposure regulates human transferrin (TF) synthesis at the mRNA level.
- The regulatory response to lead differs between human and mouse TF genes.
- This study highlights a specific mechanism of lead toxicity impacting human iron transport protein synthesis.