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Mercury contamination of rat amylin mimics vasoactivity and cytotoxic effects
Heiko A Golpon1, Annette Püchner, Lothar Schmidt
1Department of Internal Medicine, Philipps University of Marburg, Baldinger Strasse, 35033, Marburg, Germany. Heiko.Golpon@medizin.uni-magdeburg.de
Abstract:
Rat amylin differs from human amylin (hIAPP) in that it lacks a fibril-forming capacity. As a consequence, toxic effects have been reported for human but not for rat amylin. This report demonstrates how a mercury contamination of commercial rat amylin imitates peptide-related vasoactive and cytotoxic effects on preparations of isolated blood vessels. The source of mercury contamination was believed related to the peptide synthesis. Thiol groups of cysteine-containing peptides are often protected by acetamidomethyl (Acm) which is cleaved by mercuric acetate.
Insights
Mercury contamination in rat amylin can mimic toxic effects typically seen with human amylin (hIAPP). This contamination, possibly from peptide synthesis, caused unexpected vasoactive and cytotoxic impacts on blood vessels.
Area of Science:
- Biochemistry
- Toxicology
- Physiology
Background:
- Human amylin (hIAPP) is known to form fibrils and exhibit toxic effects, unlike rat amylin.
- Rat amylin typically does not display fibril-forming capacity or associated toxicity.
- Contamination in peptide preparations can alter experimental results.
Purpose of the Study:
- To investigate the cause of unexpected vasoactive and cytotoxic effects observed with commercial rat amylin.
- To determine if mercury contamination could be responsible for these effects.
- To understand the implications of contamination in peptide-based research.
Main Methods:
- Analysis of commercial rat amylin for contaminants.
- In vitro testing of rat amylin preparations on isolated blood vessels.
- Assessment of vasoactive and cytotoxic responses.
Main Results:
- Commercial rat amylin exhibited vasoactive and cytotoxic effects on isolated blood vessels.
- Mercury was identified as a contaminant in the rat amylin preparation.
- The observed effects mimicked those typically associated with human amylin.
Conclusions:
- Mercury contamination in rat amylin can induce toxicity and vasoactivity, mimicking human amylin (hIAPP) effects.
- Peptide synthesis, particularly the use of mercuric acetate to cleave acetamidomethyl (Acm) protecting groups, is a likely source of contamination.
- Researchers must be vigilant about potential contaminants in synthetic peptides to ensure experimental validity.
