Bak is typically induced by oxidative stress and its levels increase as people age. The researchers wanted to see whether its absence would prevent the age-related hearing loss that is associated with the death of certain sensory hair, nerve and membrane cells in the inner ear.
Hearing tests showed that Bak-deficient middle-aged mice were found to have hearing levels comparable to that of young mice. In addition, fewer of the critical hearing cells died, compared with so-called wild type mice that did not have the protein deficiency.
To examine how resistant the inner ear cells of the Bak-deficient mice were, the researchers exposed cells to a chemical that causes oxidative stress. Such stress generally induces Bak expression in inner ear cells.
There was only minor loss of cochlear cells at all doses of the stressor chemical, in contrast with the level observed in wild-type animals. The researchers concluded that Bak promotes cochlear cell death in response to oxidative stress.
"This paper clearly shows us that oxidative stress causes hearing loss," said Jinze Xu, a postdoctoral fellow in Leeuwenburgh's group, and second author of the paper.
So if oxidative stress triggers damage and death of hearing-related cells, enhancing the antioxidant defenses of the mitochondria should reduce such damage.
The researchers found that both in animals that had excess amounts of an enzyme that scavenges reactive oxygen species, as well as in those who were fed certain antioxidants orally, onset of age-related hearing loss was delayed.
"It looks like a viable biological target that may be applicable to drug use," Leeuwenburgh said. "The issue is always timing when to start antioxidan
|Contact: Czerne M. Reid|
University of Florida