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Free Radicals Balance Out

27 January 2006 (All day)
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Susumu Nishinaga / Photo Researchers Inc.

Hidden gems.
Otoconia crystals in the inner ear are essential for balance.

Oxygen free radicals may have a softer side. The molecules--well known for their toxic effects on cells--appear to play a key role in the development of balance in the inner ear, according to a new study. The find is one of the first signs that such reactive oxygen species can build as well as destroy.

In mammals, the inner ear contains tiny mineralized crystals called otoconia that help an animal stay upright. When the head accelerates or decelerates, they bend the sensory hair cells and send a signal to the brain telling it which way is up. If they move too quickly or get dislodged--by a roller-coaster ride, for example--they trigger feelings of dizziness and nausea. Scientists have long puzzled over how the particles form, however.

Now, a strain of mice with major balance problems has provided scientists with new clues about the genesis of otoconia. Medical researcher Botond Banfi of the University of Iowa in Iowa City, who usually studies free radicals produced by the immune system, was working to determine the role of a newly recognized gene called Noxo1. In a search for mutant mice that might be missing the gene, Banfi and colleagues came upon a strain called head slant. The mice have trouble walking and when placed on their backs do not attempt to right themselves. In cages, they often try to crawl upside-down on the bars that cover the cage.

The inner ears of the mutant mice looked completely normal, but they lacked otoconia. Upon further investigation, the team found that Noxo1 is highly expressed in the embryonic inner ear of normal mice, though its expression drops sharply after birth. Mutations in a related gene--Nox3--also cause loss of balance in mice, according to a 2004 report. In cell-based tests, Banfi and his colleagues showed that Noxo1 and Nox3 work together to produce superoxide, a precursor of oxygen free radicals. Taken together, the results suggest that oxygen radicals play a key role in otoconia formation, the team reports on 24 January in Current Biology.

The researchers don't yet know the exact chemical reactions that produce the free radicals, but the work "quite solidly establishes a new role for reactive oxygen in development," says ageing researcher Karl-Heinz Krause of the University of Geneva in Switzerland. Banfi says that the related genes expressed in a variety of tissues suggest that reactive oxygen species will turn up in other surprising roles. "There was a concept that reactive oxygen species are bad," he says, "but they can do more than harm cells."

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