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When heme attacks: After trauma, the molecule that makes life possible rampages

(Philadelphia, PA) Heme, the iron-bearing, oxygen-carrying core of hemoglobin, makes it possible for blood to carry oxygen, but researchers from the University of Pennsylvania School of Medicine have determined how free-floating heme can also make traumatic events worse by damaging tissue. The Penn researchers present their findings in the October 2nd issue of the journal Nature. Fortunately, the researchers also identified a chemical that can be targeted by drug developers to impede the deleterious effects of free-floating heme.

Following a traumatic event such as an accident, a stroke, a heart attack or even surgery heme floods the spaces between and inside cells and exacerbates the damage. It does so by shutting down an important cell membrane channel, an action that kills neurons and constricts blood vessels. While investigating this process, the researchers also determined that a chemical called NS1619 restores the function of the cell membrane channel. NS1619 and its derivatives could be the source for a new drug one that prevents the secondary events that worsen trauma damage.

"Following a heart attack, a stroke, or any really severe physical injury, heme is literally shaken loose from hemoglobin," said Xiang Dong Tang, MD, PhD, Staff Scientist in Penn's Department of Physiology. "Normally, cells can compensate and recycle loose heme. But when larger concentrations are released, heme can gum up the works, specifically the Maxi-K ion channel, a cell membrane protein important for blood vessel relaxation and neuron excitability."

Maxi-K is a channel that moves potassium ions out of cells. In the Nature paper, Tang and his colleagues prove that the Maxi-K protein possesses sites that bind heme. If these sites were removed or altered, heme could not effect Maxi-K proteins.

"Maxi-K is found in the lining of blood vessels. When it is turned off, the vessel constricts, increasing blood pressure, which is decidedly not beneficial follo
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Contact: Greg Lester
lesterg@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
1-Oct-2003


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