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Muscle cells self-destruct rather than grow with use

Muscle cells that should grow stronger with use instead self-destruct when a protein called BAG3 isn't around, researchers have shown.

Mice missing BAG3 seem fine at birth, but when they start using their muscles to breathe and stand, muscle cells rapidly degenerate and cannot regenerate, says Dr. Shinichi Takayama, cell and molecular biologist at the Medical College of Georgia.

The finding illustrates BAG3's importance in maintaining mature skeletal muscle, researchers say in the September issue of the American Journal of Pathology.

They hope it will lead to prevention of muscle atrophy that characterizes diseases such as muscular dystrophy, heart failure and a lesser-known condition called myofibril myopathy, which affects the tiniest muscle fibers. Dr. Takayama believes his BAG3 knockout is a model for the worst case of this rare disease.

"Basically we think that the degeneration starts because of usage of muscles, which should make them stronger," Dr. Takayama says. Instead, cells previously dormant in utero start dying. "They cannot breathe, they cannot use their muscles and they die quickly," he says of BAG3 knockout mice.

"When a muscle contraction happens, cytoskeletal degeneration occurs naturally," he says. Interestingly, degeneration normally stimulates regeneration, but not in these mice. Instead cells take another option: when they can't be fixed, they kill themselves.

This mass suicide in the absence of BAG3 is not a huge surprise. Dr. Takayama, the first to clone five members of the BAG family, says the proteins help regulate heat shock protein 70, which helps other proteins fold and function properly. The BAG family also has an anti-death function called antiapoptosis. Dr. Takayama is still dissecting the relationship between the anti-death function and BAG's regulatory role with the heat shock protein. "If protein folding is not happening to a cell, that cell should die, so I think t
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
30-Aug-2006


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