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Speciation and Bioavailability Measurements of Environmental Plutonium Using Diffusion in Thin Films
Published on: November 9, 2015
An iron-dependent and transferrin-mediated cellular uptake pathway for plutonium.
Mark P Jensen1, Drew Gorman-Lewis, Baikuntha Aryal
1Chemical Sciences and Engineering Division, Argonne National Laboratory, Argonne, Illinois, USA. mjensen@anl.gov
Nature Chemical Biology
|June 28, 2011
Summary
Plutonium uptake by cells occurs via the iron pathway, specifically through the transferrin receptor. Cellular plutonium retention is influenced by how plutonium and iron bind to the transferrin protein.
Area of Science:
- Biochemistry
- Toxicology
- Cell Biology
Background:
- Plutonium is a toxic synthetic element with no biological role.
- Human ingestion of plutonium leads to strong retention.
- Understanding plutonium's cellular uptake is crucial for toxicology and health risk assessment.
Purpose of the Study:
- To investigate the mechanism of plutonium cellular uptake.
- To determine if plutonium utilizes the iron acquisition pathway.
- To identify factors influencing plutonium-transferrin complex interaction with cellular receptors.
Main Methods:
- Small-angle X-ray scattering (SAXS) for structural analysis.
- Receptor binding assays to study protein-receptor interactions.
- Synchrotron X-ray fluorescence microscopy for elemental mapping.
Main Results:
- Rat adrenal gland (PC12) cells internalize plutonium via receptor-mediated endocytosis of serum transferrin, the primary iron uptake pathway.
- Only plutonium-transferrin complexes with plutonium in the C-lobe and iron in the N-lobe (Pu(C)Fe(N)Tf) adopt the correct conformation for transferrin receptor binding.
- Differences between transferrin's N- and C-lobes restrict, but do not completely block, cellular plutonium uptake.
Conclusions:
- Plutonium exploits the major iron acquisition pathway for cellular entry.
- The specific binding site of plutonium and iron on transferrin dictates cellular uptake efficiency.
- Differential metal binding to transferrin lobes influences plutonium's biological availability and toxicity.
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