Athens, Ga. – There is increasing interest in the health effects of the common metallic element mercury. The versatile chemical properties of this silvery metal, known since antiquity and named for the messenger of the gods, have led to its use in such diverse applications as cosmetics, antiseptics, metallurgical mixtures and industrial catalysts.
Now, the U.S. Department of Energy has awarded a $1.8 million grant to a team headed by University of Georgia microbiologist Anne Summers to examine what happens to proteins when living cells are exposed to mercury.
“The practical application of this project is to identify especially vulnerable and slowly repaired proteins as biomarkers for detecting the most subtle mercury damage long before it could be manifest by more obvious changes such as delayed cell division or the formation of mutations,” said Summers. “Although we will study these phenomena in bacteria, many potential target proteins in plants and animals have evolved from counterparts in bacteria.”
Others involved in the project are protein chemist Susan Miller at the University of California-San Francisco and biological mass spectrometrist Mary Lipton at the Department of Energy Pacific Northwest National Laboratory.
Although children once played freely with the fascinating shiny, heavy liquid released from broken glass thermometers and had their cuts and scrapes painted with the bright orange of Merthiolate, such uses have been phased out as the environmental burden of this very mobile toxic element has become apparent.
Summers already studies how bacteria protect themselves from naturally occurring deposits of mercury ores such as those in southern Europe, northern Africa, China, Russia and western North America. Bacteria can biochemically convert the two most toxic forms of mercury into comparatively harmless (for bacteria) volatile mercury vapor.
Understanding the resistance mechanism provided clues about why cells are vulnerable to poisoning by mercury.
“Superficially, this seems obvious,” said Summers, “since mercury forms strong bonds with compounds that contain the element sulfur, and life’s chemistry uses many sulfur-containing compounds for everything from production of cellular energy to protection from radiation damage.”
The very abundant small sulfur compounds made by these ubiquitous cellular defense systems are, in principle, capable of “mopping up” mercury and flushing it out of the cell. The paradox of mercury poisoning is that cells can be damaged by mercury concentrations one thousand-fold lower than the concentrations of their abundant natural defense molecules. It seems that some proteins bind mercury so tightly that these natural cellular compounds can’t remove it.
Seeing changes in a cell’s entire complement of proteins is only recently possible through a type of analysis called proteomics. Enabled by advances in mass spectrometry, proteomics reveals alterations in each protein in treated cells compared to its counterpart in untreated cells.
In prior work with the proteins of the mercury resistance system, Summers and her collaborators found that mass spectrometry can detect proteins with attached mercury atoms. They have also shown that one of the bacterial resistance proteins can pull mercury right off a poisoned cellular protein.
Now, they will look at the full array of proteins in the cell to find those readily modified at sub-lethal mercury concentrations, and, by tracking cells over time after exposure, they will see which proteins can be restored by basic cellular repair processes and how repair differs when the mercury resistance genes are present.
The methods they devise to monitor mercury damage can later be applied to mercury-exposed plants and animals which, unfortunately, lack the potent mercury resistance systems found in bacteria.
The Department of Energy’s Office of Biological and Environmental Research is funding this research because it is interested in understanding the biogeochemical processes that influence mercury fate and transport in the subsurface. Understanding these processes will help in developing remediation approaches for addressing mercury contamination that occurred at several of DOE’s former nuclear-fuel-refining facilities.