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To further test the enzyme's role in blood vessel lining damage, the scientists then showed that metal chelators and antioxidants lessen the mercury-induced activation of the enzyme in endothelial cells. This portion of the study showed that different types of mercury affect the cells in different ways.

In the three forms of mercury methylmercury chloride, (environmental form), thimerosal (pharmaceutical form) and mercuric chloride (inorganic form) the enzyme activation was prevented by metal chelators, which are organic chemicals that bind with and remove free metal ions from substances.

The power of methylmercury chloride to activate the enzyme was also affected by antioxidants, including vitamin C, suggesting that this form of the metal generates free radicals. This is the form of mercury most closely associated with the food supply.

"Chelators overall did a better job than antioxidants at protecting against mercury activation of the enzyme," said Thomas Hagele, first author of the study and an undergraduate researcher in Parinandi's lab. "This shows that activation of the enzyme is not isolated to one location in the cell. Since we can protect against the enzyme activation with both chelators and antioxidants, that means a few different types of activation are likely to occur, depending on the toxin."

This research is not just about mercury, noted Parinandi, also an assistant professor of pulmonary, critical care and sleep medicine. Mercury in this case acts as a model for other toxins that have similar effects on blood vessel walls, pointing to what happens in the body when toxic substances are a factor in causing diseases.

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Contact: Emily Caldwell
emily.caldwell@osumc.edu
614-293-3737
Ohio State University Medical Center
30-May-2007