radicals tell mice what's up and down
TRANSCRIPT
Outsource Your
MSDS Authoring to
Wercs Professional
Services and Become
Compliant Today!
For more than 20 years, The Wercs has
provided the chemical industry with the most
comprehensive MSDS authoring software.
Now, no matter how large or small your
organization, this same software can benefit
you today through Wercs Professional
Services and its team of certified authors.
With the Wercs Professional Services,
you can now easily:
• Subcontract a portion or all your MSDS
authoring with a quick turnaround time
• Keep your MSDSs up to date and
compliant, at all times
• Delegate difficult geographies, such as Asia,
Europe and the Americas
• Send us your surge requirements
• Revise MSDSs for the Canadian three-year
review requirement
Obères® Professional Services
Request more at AdlnfoNow.org
8 8 C & E N / F E B R U A R Y 1 3 . 2 0 0 6
RADICALS TELL MICE WHAT'S UP AND DOWN Reactive oxygen species are found to play a role in helping mice develop a sense of balance
Ν BIOLOGICAL CONTEXTS, THOSE IRASCIBLE
atoms and molecules known as free radicals have for decades been besmirched as good-for-nothing upstarts that emerge from various cellular processes only to
vandalize the delicate biochemical landscape around them. That's why the discovery in recent years of a few enzymes that deliberately produce reactive oxygen species (ROS), a type of free radical, has been so puzzling.
Now, a team of nine researchers at four institutions has found evidence that ROS produced by one of these NADPH oxidase (NOX) enzymes is pivotal to the development of a sense of up and down, at least for a strain of mutant mice with severe balance problems (Curr. Biol. 2006,16,208). The finding indicates that free radicals are not always bad to the bone, says research team leader Botond Bânfi, a cell biologist at the University of Iowa, Iowa City.
"Most of the work for the last 30 years has followed the paradigm that reactive oxygen is something that is best to get rid of," comments medical pathologist J. David Lambeth of Emory University, one of the first scientists to identify NOX enzymes that generate ROS. "The new work really provides evidence for a novel positive function for reactive oxygen species that was previously unexpected."
Bânfi and his collaborators have shown that ROS are important players in the healthy formation of calcium carbonate particles called otoliths that form above inner-ear sensory hair cells during embryonic development of vertebrates, among them mice and humans. The otolith-cell arrangements function as motion sensors that help animals sense the direction of gravity.
The discovery of an uncharacteristically positive role for oxygen radicals emerged from the researchers, quest to uncover the function of a regulatory component of a NOX complex, Noxol, a relative of a regulatory protein that previously had been found in phagocytes, a type of immune cell.
The researchers reasoned that their investigation would be greatly aided if they could find a mouse strain with a mutated version of Noxol. Using genetic and genomic analysis techniques, they found what they were looking for—a mouse mutant known as "head
slant" because of the awkward way it holds its head and body. The scientists determined that this animal's Noxol gene bears a single extra nucleotide that most likely yields a 34-amino-acid peptide rather than the normal 349-amino-acid Noxol protein.
Head-slant mice hobble, fall over, and sometimes move about on their backs, as though they do not know which way is up. "They are like drunk people without the ugliness of being drunk," Bânfi says.
That behavior, the researchers learned
EAR SAND Otoliths, calcium carbonate particles (above) that form in the inner ear and are important for a sense of balance, are absent in a mutant mouse strain (bottom).
from microanatomical studies, is a result of the complete absence of otoliths in the animals' inner ears. And this is where the beneficial role of ROS becomes apparent.
The mutated Noxol component reduces the ability of the NADPH oxidase complex in the mutant mice's inner ears to generate superoxide radicals during embryonic development when otoliths form, Bânfi explains. The researchers conjecture that in normal animals, ROS may help the vesicles in which otoliths form become permeable to calcium and other components involved in otolith formation. "The next exciting questions for us is to find out the mechanism here," Bânfi says.-IVAN AMAT0
W W W . C E N - 0 N L I N E . O R G
MSDS Authoring Services
Cau us at 1-800-572-6501 to learn more, or visit ou·
i»vebs:îe at www.wercsprofessionalservices.com