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Published on: March 1, 2017
Lead causes human fibroblasts to mis-sort arylsulfatase A
1Department of Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, New Brunswick, NJ 08901-8525, USA.
Toxicology
|August 23, 2001
Summary
Lead exposure reduces critical arylsulfatase A (ARSA) enzyme levels in children with specific gene variants. This study reveals lead disrupts ARSA trafficking, decreasing its intracellular accumulation and potentially impacting nervous system function.
Area of Science:
- Biochemistry
- Neuroscience
- Toxicology
Background:
- Lead exposure is linked to cognitive and behavioral deficits in children.
- Reduced arylsulfatase A (ARSA) enzyme activity, due to genetic factors and lead exposure, may impair nervous system function.
- Previous studies showed lead decreases ARSA protein levels in fibroblasts with pseudodeficient ARSA genes.
Purpose of the Study:
- To investigate how lead affects the biosynthesis, trafficking, and turnover of ARSA in human fibroblasts.
- To understand the cellular mechanisms underlying lead-induced reductions in intracellular ARSA levels.
Main Methods:
- Human fibroblasts were cultured with lead acetate (20 microM).
- Analyzed ARSA protein levels, mRNA expression, intracellular degradation rates, and enzyme trafficking.
- Measured cellular proliferation rates.
Main Results:
- Lead exposure increased fibroblast proliferation by 44-58%.
- A 33% decrease in newly synthesized intracellular ARSA accumulation was observed.
- Lead exposure redirected newly synthesized ARSA to the secretion pathway, reducing intracellular enzyme levels.
- Increased ARSA degradation or decreased mRNA levels were not the cause.
Conclusions:
- Lead exposure decreases intracellular ARSA levels by altering enzyme trafficking, not degradation or synthesis.
- This disruption in ARSA sorting to lysosomes may contribute to neurodevelopmental issues in lead-exposed children, especially those with ARSA gene variants.
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