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UT, Georgia researchers win grant to continue studies into cell membrane repair |
| By
Jim Winkler |
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Nov 5, 2008
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A team of scientists at The University of Toledo and the Medical College of Georgia has received a two-year, $360,000 grant from the National Institutes of Health to learn more about the function of enzymes called calpains in repairing damaged cell membranes.
The grant will allow the principal investigator, Dr. Ronald Mellgren, professor of physiology and pharmacology, to continue his collaborative studies with a team of researchers at the Medical College of Georgia headed by Dr. Paul McNeil, aimed at understanding the role of the calcium-requiring, protein-digesting enzymes.
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| Dr. Ronald Mellgren of the College of Medicine has been studying calpains for more than three decades. |
Mechanical and other kinds of moment-to-moment stresses and strains chip away at cells in tissues, a process that eventually can cause their outer membranes to break. For example, cell membranes are damaged when a person is seriously injured in a traffic accident or experiences a heart attack. Damage to cell membranes even occurs during the normal wear and tear of physical exercise, including in muscle cells during contraction, studies by McNeil have shown.
“While having a strong cell membrane is part of the protection against mechanical damage, a compelling body of evidence now indicates that it is also important to have an efficient, rapid way to repair the cell membrane once damage has occurred,” Mellgren explained. “Some studies now indicate that skeletal muscle and heart muscle disease associated with one form of muscular dystrophy are caused by failure to repair ongoing mechanical damage to the muscle cell membrane.”
In the body, cells are bathed on the outside with fluid containing large amounts of dissolved calcium ion, known for years to be required for the repair of damaged cell membranes.
Mellgren and McNeil found that one role for calcium is activation of calpains to break down the proteinaceous cell skeleton — the cytoskeleton — near the site of damage. It is thought that this clears a pathway for repair components inside the cell to migrate to the damaged membrane and form a “patch.”
The observation provided the foundation for the studies that recently have been funded.
The new grant will fund studies to determine which of the many types of calpain enzymes in cells are required for repairing membrane damage and show which proteins calpains must digest for repairs to occur.
Other studies will determine if membrane repair is facilitated by interaction of calpains with proteins that normally are present in the fluid surrounding cells. These proteins could interact with calpains where they are exposed at sites of membrane damage.
Mellgren, a native of Des Moines, Iowa, joined the College of Medicine in 1978 and has been studying calpains for more than 30 years. He discovered calpain-1, the type of calpain that is most active in cells, shortly after joining the former Medical College of Ohio as an assistant professor and said he “is gratified to have seen calpain research grow.”
The prestigious journal Nature has asked Mellgren to write an article for its “News and Views” section in an upcoming issue on two crystallographic studies of calpain joined with its natural inhibitor protein, calpastatin.
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