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Little yellow molecule comes up big

Bilirubin has been a mystery of a molecule, associated with better health if there's just a little more than normal, but best known for being at the root of the yellow color in jaundice and, at high levels, for causing brain damage in newborns. Johns Hopkins scientists have now solved the enigma of how this toxic molecule can also be beneficial.

In the current online edition of the Proceedings of the National Academy of Sciences, the research team reports that bilirubin and the enzyme that makes it appear to be the body's most potent protection against oxidative damage. The finding may one day help improve treatment of stroke, heart attack and even cognitive decline following heart bypass surgery.

"So potent an anti-oxidant is bilirubin that it displaces glutathione, the molecule believed for 80 years to be the most important cellular anti-oxidant," says Solomon Snyder, M.D., director of neuroscience at the Johns Hopkins School of Medicine.

"There are some very elegant studies in the literature that tie slightly elevated bilirubin levels to better alertness in newborns, a lower risk of coronary artery disease and cancer in adults, and less damage from stroke in animal models. But these findings went against what people thought they knew about bilirubin, and the results were largely shrugged off," adds Snyder. "Now they make sense."

Known as the toxic yellow molecule at the end of the biologic degradation of hemoglobin, the "red" in red blood cells, bilirubin also has long been known to react with the highly reactive forms of oxygen responsible for practically all cellular damage. However, there's so little bilirubin in cells -- roughly a thousand times less than the amount of oxidants -- that it wasn't thought to actually contribute to cells' protection.

To test their idea that these tiny amounts of bilirubin had a big job, the scientists used a research tool called RNA interference to "zip up" the RNA for biliverdin re
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
25-Nov-2002


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