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Worm provides clues about preventing damage caused by low-oxygen during stroke, heart attack
Date:1/29/2009

Neurobiologists at Washington University School of Medicine in St. Louis have identified pathways that allow microscopic worms to survive in a low-oxygen, or hypoxic, environment.

They believe the finding could have implications for conditions such as stroke, heart attack and cancer. Sensitivity to low oxygen helps determine how damaging those medical conditions can be. The researchers report their findings in the Jan. 30 issue of the journal Science.

"In stroke and heart attack, cells die because they lack oxygen," explains principal investigator C. Michael Crowder, M.D., Ph.D. "In cancer, the opposite is true. Cancer cells are hypoxia-resistant in many cases, and their potential to spread throughout the body tends to correlate with their degree of hypoxia resistance."

Crowder says it may be possible to develop more effective therapies for stroke and heart attack, on one hand, and cancer, on the other, when scientists better understand how cells protect themselves from oxygen deprivation. In the case of stroke and heart attack, therapies would involve making healthy cells resistant to hypoxia. Cancer therapies might work more effectively if it were possible to make hypoxia-resistant cells more vulnerable to low oxygen levels.

In new experiments, Crowder's team manipulated genes in the worm Caenorhabditis elegans to alter the organism's sensitivity to a low-oxygen environment. They did that by identifying a gene that controls the translation of genetic information into specific proteins. Mutant copies of the gene cut translation rates in half, which conferred 100% survival to the animals compared to 100% death in non-mutant worms.

Crowder says that inhibiting translation likely protects cells from hypoxia by reducing energy consumption because making proteins consumes a lot of energy. The researchers were surprised by the degree of resistance to hypoxia when the translation rate was cut. They wanted to
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Contact: Jim Dryden
jdryden@wustl.edu
314-286-0110
Washington University School of Medicine
Source:Eurekalert

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